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Full-Text Articles in Cardiovascular Diseases

The Effects Of Demographics And Risk Factors On The Morphological Characteristics Of Human Femoropopliteal Arteries, Sayed Ahmadreza Razian, Majid Jadidi, Alexey Kamenskiy Mar 2023

The Effects Of Demographics And Risk Factors On The Morphological Characteristics Of Human Femoropopliteal Arteries, Sayed Ahmadreza Razian, Majid Jadidi, Alexey Kamenskiy

UNO Student Research and Creative Activity Fair

Background: Disease of the lower extremity arteries (Peripheral Arterial Disease, PAD) is associated with high morbidity and mortality. During disease development, the arteries adapt by changing their diameter, wall thickness, and residual deformations, but the effects of demographics and risk factors on this process are not clear.

Methods: Superficial femoral arteries from 736 subjects (505 male, 231 female, 12 to 99 years old, average age 51±17.8 years) and the associated demographic and risk factor variables were used to construct machine learning (ML) regression models that predicted morphological characteristics (diameter, wall thickness, and longitudinal opening angle resulting from the …


Genetic Architecture Of Spatial Electrical Biomarkers For Cardiac Arrhythmia And Relationship With Cardiovascular Disease, William J Young, Jeffrey Haessler, Jan-Walter Benjamins, Linda Repetto, Jie Yao, Aaron Isaacs, Andrew R Harper, Julia Ramirez, Sophie Garnier, Stefan Van Duijvenboden, Antoine R Baldassari, Maria Pina Concas, Thuyvy Duong, Luisa Foco, Jonas L Isaksen, Hao Mei, Raymond Noordam, Casia Nursyifa, Anne Richmond, Meddly L Santolalla, Colleen M Sitlani, Negin Soroush, Sébastien Thériault, Stella Trompet, Stefanie Aeschbacher, Fariba Ahmadizar, Alvaro Alonso, Jennifer A Brody, Archie Campbell, Adolfo Correa, Dawood Darbar, Antonio De Luca, Jean-François Deleuze, Christina Ellervik, Christian Fuchsberger, Anuj Goel, Christopher Grace, Xiuqing Guo, Torben Hansen, Susan R Heckbert, Rebecca D Jackson, Jan A Kors, Maria Fernanda Lima-Costa, Allan Linneberg, Peter W Macfarlane, Alanna C Morrison, Pau Navarro, David J Porteous, Peter P Pramstaller, Alexander P Reiner, Lorenz Risch, Ulrich Schotten, Xia Shen, Gianfranco Sinagra, Elsayed Z Soliman, Monika Stoll, Eduardo Tarazona-Santos, Andrew Tinker, Katerina Trajanoska, Eric Villard, Helen R Warren, Eric A Whitsel, Kerri L Wiggins, Dan E Arking, Christy L Avery, David Conen, Giorgia Girotto, Niels Grarup, Caroline Hayward, J Wouter Jukema, Dennis O Mook-Kanamori, Morten Salling Olesen, Sandosh Padmanabhan, Bruce M Psaty, Cristian Pattaro, Antonio Luiz P Ribeiro, Jerome I Rotter, Bruno H Stricker, Pim Van Der Harst, Cornelia M Van Duijn, Niek Verweij, James G Wilson, Michele Orini, Philippe Charron, Hugh Watkins, Charles Kooperberg, Henry J Lin, James F Wilson, Jørgen K Kanters, Nona Sotoodehnia, Borbala Mifsud, Pier D Lambiase, Larisa G Tereshchenko, Patricia B Munroe Mar 2023

Genetic Architecture Of Spatial Electrical Biomarkers For Cardiac Arrhythmia And Relationship With Cardiovascular Disease, William J Young, Jeffrey Haessler, Jan-Walter Benjamins, Linda Repetto, Jie Yao, Aaron Isaacs, Andrew R Harper, Julia Ramirez, Sophie Garnier, Stefan Van Duijvenboden, Antoine R Baldassari, Maria Pina Concas, Thuyvy Duong, Luisa Foco, Jonas L Isaksen, Hao Mei, Raymond Noordam, Casia Nursyifa, Anne Richmond, Meddly L Santolalla, Colleen M Sitlani, Negin Soroush, Sébastien Thériault, Stella Trompet, Stefanie Aeschbacher, Fariba Ahmadizar, Alvaro Alonso, Jennifer A Brody, Archie Campbell, Adolfo Correa, Dawood Darbar, Antonio De Luca, Jean-François Deleuze, Christina Ellervik, Christian Fuchsberger, Anuj Goel, Christopher Grace, Xiuqing Guo, Torben Hansen, Susan R Heckbert, Rebecca D Jackson, Jan A Kors, Maria Fernanda Lima-Costa, Allan Linneberg, Peter W Macfarlane, Alanna C Morrison, Pau Navarro, David J Porteous, Peter P Pramstaller, Alexander P Reiner, Lorenz Risch, Ulrich Schotten, Xia Shen, Gianfranco Sinagra, Elsayed Z Soliman, Monika Stoll, Eduardo Tarazona-Santos, Andrew Tinker, Katerina Trajanoska, Eric Villard, Helen R Warren, Eric A Whitsel, Kerri L Wiggins, Dan E Arking, Christy L Avery, David Conen, Giorgia Girotto, Niels Grarup, Caroline Hayward, J Wouter Jukema, Dennis O Mook-Kanamori, Morten Salling Olesen, Sandosh Padmanabhan, Bruce M Psaty, Cristian Pattaro, Antonio Luiz P Ribeiro, Jerome I Rotter, Bruno H Stricker, Pim Van Der Harst, Cornelia M Van Duijn, Niek Verweij, James G Wilson, Michele Orini, Philippe Charron, Hugh Watkins, Charles Kooperberg, Henry J Lin, James F Wilson, Jørgen K Kanters, Nona Sotoodehnia, Borbala Mifsud, Pier D Lambiase, Larisa G Tereshchenko, Patricia B Munroe

Faculty, Staff and Student Publications

The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic …


Chronic Kidney Disease Promotes Cerebral Microhemorrhage Formation, Chuo Fang, Wei Ling Lau, Jiahong Sun, Rudy Chang, Adrian Vallejo, Donghy Lee, Jihua Liu, Han Liu, Yu-Han Hung, Yitong Zhao, Annlia Paganini-Hill, Rachita K. Sumbria, David H. Cribbs, Mark J. Fisher Feb 2023

Chronic Kidney Disease Promotes Cerebral Microhemorrhage Formation, Chuo Fang, Wei Ling Lau, Jiahong Sun, Rudy Chang, Adrian Vallejo, Donghy Lee, Jihua Liu, Han Liu, Yu-Han Hung, Yitong Zhao, Annlia Paganini-Hill, Rachita K. Sumbria, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

Background

Chronic kidney disease (CKD) is increasingly recognized as a stroke risk factor, but its exact relationship with cerebrovascular disease is not well-understood. We investigated the development of cerebral small vessel disease using in vivo and in vitro models of CKD.

Methods

CKD was produced in aged C57BL/6J mice using an adenine-induced tubulointerstitial nephritis model. We analyzed brain histology using Prussian blue staining to examine formation of cerebral microhemorrhage (CMH), the hemorrhagic component of small vessel disease and the neuropathological substrate of MRI-demonstrable cerebral microbleeds. In cell culture studies, we examined effects of serum from healthy or CKD patients and …


Prevention Of Doxorubicin-Induced Cardiotoxicity By A Coumestan Analogue, Psoralidin, Mujtaba H. Shah, Myia Aiges, Kota V. Ramana Feb 2023

Prevention Of Doxorubicin-Induced Cardiotoxicity By A Coumestan Analogue, Psoralidin, Mujtaba H. Shah, Myia Aiges, Kota V. Ramana

Annual Research Symposium

Natural phenolic compound Psoralidin limits cardiotoxicity associated with Doxorubicin


Association Of Circulating Mtdna With Cvd In Hemodialysis Patients And In Vitro Effect Of Exogenous Mtdna On Cardiac Microvascular Inflammation, Zhen Fan, Ya Feng, Li Zang, Yi Guo, Xiao-Yi Zhong Feb 2023

Association Of Circulating Mtdna With Cvd In Hemodialysis Patients And In Vitro Effect Of Exogenous Mtdna On Cardiac Microvascular Inflammation, Zhen Fan, Ya Feng, Li Zang, Yi Guo, Xiao-Yi Zhong

Faculty, Staff and Student Publications

BACKGROUND: Chronic kidney disease (CKD) patients sustain a fairly high prevalence of cardiovascular disease (CVD). Microvascular inflammation is an early manifestation of CVD, and the released mitochondrial DNA (MtDNA) has been proposed to be a crucial integrator of inflammatory signals. Herein, the aim of this study was to determine the relationship between CVD, microvessel, and circulating MtDNA in the settings of uremia.

METHODS: Forty-two maintenance hemodialysis (MHD) patients and 36 health controls were enrolled in this study. Plasma cell-free MtDNA was detected by TaqMan-based qPCR assay. CVD risk markers including high-sensitive C-reactive protein (Hs-CRP), monocyte chemoattractant protein-1 (MCP-1), fibrinogen, and …


Association Between P2y12 Inhibitor Reloading And In-Hospital Outcomes For Patients With Non-St-Segment Elevation Acute Coronary Syndrome Already On Chronic P2y12 Receptor Inhibitors Therapy In China: Findings From The Ccc-Acs (Improving Care For Cardiovascular Disease In China-Acute Coronary Syndrome) Project, Yintang Wang, Yu Geng, Ou Zhang, Qin Xu, Yajun Xue, Boda Zhou, Ping Zhang Feb 2023

Association Between P2y12 Inhibitor Reloading And In-Hospital Outcomes For Patients With Non-St-Segment Elevation Acute Coronary Syndrome Already On Chronic P2y12 Receptor Inhibitors Therapy In China: Findings From The Ccc-Acs (Improving Care For Cardiovascular Disease In China-Acute Coronary Syndrome) Project, Yintang Wang, Yu Geng, Ou Zhang, Qin Xu, Yajun Xue, Boda Zhou, Ping Zhang

Faculty, Staff and Student Publications

BACKGROUND: The association between P2Y12 receptor inhibitors reloading and in-hospital outcomes in non-ST-segment elevation acute coronary syndrome (NSTEACS) patients who were on chronic P2Y12 receptor inhibitors therapy remained underdetermined.

METHODS: The Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS project) is a national registry active from November 2014 to December 2019. 4790 NSTEACS patients on chronic P2Y12 receptor inhibitors therapy were included. Cox proportional hazard models, Kaplan-Meier curves, and subgroup analyses were conducted.

RESULTS: The NSTEACS patients who received reloading of P2Y12 receptor inhibitors were younger and had fewer comorbid conditions. The reloading group had a lower risk …


Acoustic Voice And Speech Biomarkers Of Treatment Status During Hospitalization For Acute Decompensated Heart Failure, Olivia M Murton, G William Dec, Robert E Hillman, Maulik D Majmudar, Johannes Steiner, John V Guttag, Daryush D Mehta Feb 2023

Acoustic Voice And Speech Biomarkers Of Treatment Status During Hospitalization For Acute Decompensated Heart Failure, Olivia M Murton, G William Dec, Robert E Hillman, Maulik D Majmudar, Johannes Steiner, John V Guttag, Daryush D Mehta

Faculty, Staff and Student Publications

This study investigates acoustic voice and speech features as biomarkers for acute decompensated heart failure (ADHF), a serious escalation of heart failure symptoms including breathlessness and fatigue. ADHF-related systemic fluid accumulation in the lungs and laryngeal tissues is hypothesized to affect phonation and respiration for speech. A set of daily spoken recordings from 52 patients undergoing inpatient ADHF treatment was analyzed to identify voice and speech biomarkers for ADHF and to examine the trajectory of biomarkers during treatment. Results indicated that speakers produce more stable phonation, a more creaky voice, faster speech rates, and longer phrases after ADHF treatment compared …


Genetic Effect On Body Mass Index And Cardiovascular Disease Across Generations, Chloé Sarnowski, Matthew P Conomos, Ramachandran S Vasan, James B Meigs, Josée Dupuis, Ching-Ti Liu, Aaron Leong Feb 2023

Genetic Effect On Body Mass Index And Cardiovascular Disease Across Generations, Chloé Sarnowski, Matthew P Conomos, Ramachandran S Vasan, James B Meigs, Josée Dupuis, Ching-Ti Liu, Aaron Leong

Faculty, Staff and Student Publications

BACKGROUND: Whether genetics contribute to the rising prevalence of obesity or its cardiovascular consequences in today's obesogenic environment remains unclear. We sought to determine whether the effects of a higher aggregate genetic burden of obesity risk on body mass index (BMI) or cardiovascular disease (CVD) differed by birth year.

METHODS: We split the FHS (Framingham Heart Study) into 4 equally sized birth cohorts (birth year before 1932, 1932 to 1946, 1947 to 1959, and after 1960). We modeled a genetic predisposition to obesity using an additive genetic risk score (GRS) of 941 BMI-associated variants and tested for GRS-birth year interaction …


Potential And Pitfalls Of Pharmacovigilance Databases In Oncology, Ilana Schlam, Michael S Ewer, Sandra M Swain Feb 2023

Potential And Pitfalls Of Pharmacovigilance Databases In Oncology, Ilana Schlam, Michael S Ewer, Sandra M Swain

Faculty, Staff and Student Publications

No abstract provided.


Multi-Ancestry Genome-Wide Association Analyses Improve Resolution Of Genes And Pathways Influencing Lung Function And Chronic Obstructive Pulmonary Disease Risk, Nick Shrine, Abril G. Izquierdo, Jing Chen, Richard Packer, Robert J. Hall, Anna L. Guyatt, Chiara Batini, Rebecca J. Thompson, Chandan Puvuluri, Vidhi Malik, Brian D. Hobbs, Matthew Moll, Wonji Kim, Ruth Tal-Singer, Per Bakke, Katherine A. Fawcett, Catherine John, Kayesha Coley, Noemi Nicole Piga, Sinjini Sikdar, Martin D. Tobin, Et Al. Jan 2023

Multi-Ancestry Genome-Wide Association Analyses Improve Resolution Of Genes And Pathways Influencing Lung Function And Chronic Obstructive Pulmonary Disease Risk, Nick Shrine, Abril G. Izquierdo, Jing Chen, Richard Packer, Robert J. Hall, Anna L. Guyatt, Chiara Batini, Rebecca J. Thompson, Chandan Puvuluri, Vidhi Malik, Brian D. Hobbs, Matthew Moll, Wonji Kim, Ruth Tal-Singer, Per Bakke, Katherine A. Fawcett, Catherine John, Kayesha Coley, Noemi Nicole Piga, Sinjini Sikdar, Martin D. Tobin, Et Al.

Mathematics & Statistics Faculty Publications

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of …


Machine Learning-Based Prediction Of Acute Mortality In Emergency Department Patients Using Twelve-Lead Electrocardiogram, Po-Cheng Chang, Zhi-Yong Liu, Yu-Chang Huang, Yu-Chun Hsu, Jung-Sheng Chen, Ching-Heng Lin, Richard Tsai, Chung-Chuan Chou, Ming-Shien Wen, Hung-Ta Wo, Wen-Chen Lee, Hao-Tien Liu, Chun-Chieh Wang, Chang-Fu Kuo Jan 2023

Machine Learning-Based Prediction Of Acute Mortality In Emergency Department Patients Using Twelve-Lead Electrocardiogram, Po-Cheng Chang, Zhi-Yong Liu, Yu-Chang Huang, Yu-Chun Hsu, Jung-Sheng Chen, Ching-Heng Lin, Richard Tsai, Chung-Chuan Chou, Ming-Shien Wen, Hung-Ta Wo, Wen-Chen Lee, Hao-Tien Liu, Chun-Chieh Wang, Chang-Fu Kuo

Faculty, Staff and Student Publications

BACKGROUND: The risk of mortality is relatively high among patients who visit the emergency department (ED), and stratifying patients at high risk can help improve medical care. This study aimed to create a machine-learning model that utilizes the standard 12-lead ECG to forecast acute mortality risk in ED patients.

METHODS: The database included patients who visited the EDs and underwent standard 12-lead ECG between October 2007 and December 2017. A convolutional neural network (CNN) ECG model was developed to classify survival and mortality using 12-lead ECG tracings acquired from 345,593 ED patients. For machine learning model development, the patients were …


Artificial Intelligence-Enabled Electrocardiographic Screening For Left Ventricular Systolic Dysfunction And Mortality Risk Prediction, Yu-Chang Huang, Yu-Chun Hsu, Zhi-Yong Liu, Ching-Heng Lin, Richard Tsai, Jung-Sheng Chen, Po-Cheng Chang, Hao-Tien Liu, Wen-Chen Lee, Hung-Ta Wo, Chung-Chuan Chou, Chun-Chieh Wang, Ming-Shien Wen, Chang-Fu Kuo Jan 2023

Artificial Intelligence-Enabled Electrocardiographic Screening For Left Ventricular Systolic Dysfunction And Mortality Risk Prediction, Yu-Chang Huang, Yu-Chun Hsu, Zhi-Yong Liu, Ching-Heng Lin, Richard Tsai, Jung-Sheng Chen, Po-Cheng Chang, Hao-Tien Liu, Wen-Chen Lee, Hung-Ta Wo, Chung-Chuan Chou, Chun-Chieh Wang, Ming-Shien Wen, Chang-Fu Kuo

Faculty, Staff and Student Publications

BACKGROUND: Left ventricular systolic dysfunction (LVSD) characterized by a reduced left ventricular ejection fraction (LVEF) is associated with adverse patient outcomes. We aimed to build a deep neural network (DNN)-based model using standard 12-lead electrocardiogram (ECG) to screen for LVSD and stratify patient prognosis.

METHODS: This retrospective chart review study was conducted using data from consecutive adults who underwent ECG examinations at Chang Gung Memorial Hospital in Taiwan between October 2007 and December 2019. DNN models were developed to recognize LVSD, defined as LVEF

RESULTS: The mean age of patients in the testing dataset was 63.7 ± 16.3 years (46.3% …


Endothelial Activation And Fibrotic Changes Are Impeded By Laminar Flow-Induced Chk1-Senp2 Activity Through Mechanisms Distinct From Endothelial-To-Mesenchymal Cell Transition, Minh T H Nguyen, Masaki Imanishi, Shengyu Li, Khanh Chau, Priyanka Banerjee, Loka Reddy Velatooru, Kyung Ae Ko, Venkata S K Samanthapudi, Young J Gi, Ling-Ling Lee, Rei J Abe, Elena Mcbeath, Anita Deswal, Steven H Lin, Nicolas L Palaskas, Robert Dantzer, Keigi Fujiwara, Mae K Borchrdt, Estefani Berrios Turcios, Elizabeth A Olmsted-Davis, Sivareddy Kotla, John P Cooke, Guangyu Wang, Jun-Ichi Abe, Nhat-Tu Le Jan 2023

Endothelial Activation And Fibrotic Changes Are Impeded By Laminar Flow-Induced Chk1-Senp2 Activity Through Mechanisms Distinct From Endothelial-To-Mesenchymal Cell Transition, Minh T H Nguyen, Masaki Imanishi, Shengyu Li, Khanh Chau, Priyanka Banerjee, Loka Reddy Velatooru, Kyung Ae Ko, Venkata S K Samanthapudi, Young J Gi, Ling-Ling Lee, Rei J Abe, Elena Mcbeath, Anita Deswal, Steven H Lin, Nicolas L Palaskas, Robert Dantzer, Keigi Fujiwara, Mae K Borchrdt, Estefani Berrios Turcios, Elizabeth A Olmsted-Davis, Sivareddy Kotla, John P Cooke, Guangyu Wang, Jun-Ichi Abe, Nhat-Tu Le

Faculty, Staff and Student Publications

BACKGROUND: The deSUMOylase sentrin-specific isopeptidase 2 (SENP2) plays a crucial role in atheroprotection. However, the phosphorylation of SENP2 at T368 under disturbed flow (D-flow) conditions hinders its nuclear function and promotes endothelial cell (EC) activation. SUMOylation has been implicated in D-flow-induced endothelial-to-mesenchymal transition (endoMT), but the precise role of SENP2 in counteracting this process remains unclear.

METHOD: We developed a phospho-specific SENP2 S344 antibody and generated knock-in (KI) mice with a phospho-site mutation of SENP2 S344A using CRISPR/Cas9 technology. We then investigated the effects of SENP2 S344 phosphorylation under two distinct flow patterns and during hypercholesteremia (HC)-mediated EC activation.

RESULT: …


Induction Of Thrombotic Thrombocytopenic Purpura By Dengue Virus Infection In A Critical Patient: Role Of Therapeutic Plasma Exchange, Rathindra Nath Biswas, Sudipta Sekhar Das, Anupam Chakrapani, Subrata Sen Jan 2023

Induction Of Thrombotic Thrombocytopenic Purpura By Dengue Virus Infection In A Critical Patient: Role Of Therapeutic Plasma Exchange, Rathindra Nath Biswas, Sudipta Sekhar Das, Anupam Chakrapani, Subrata Sen

Faculty, Staff and Student Publications

Thrombotic thrombocytopenic purpura (TTP) secondary to dengue fever is a very unusual occurrence. Both conditions are fatal and can result in significant mortality and morbidity if left untreated. In this case, we present a young lady who suffered dengue fever followed by microangiopathic anemia, thrombocytopenic purpura, and altered sensorium. Investigations revealed microangiopathic hemolysis; there was no evidence of disseminated intravascular coagulation. As soon as, we diagnosed the patient as having TTP, we treated her with serial plasma exchange therapy, steroids, and monoclonal antibodies such as rituximab. The patient responded very well to the treatment and completely recovered from neurological symptoms …


Cytosolic Dna Sensing Protein Pathway Is Activated In Human Hearts With Dilated Cardiomyopathy, Leila Rouhi, Sirisha M Cheedipudi, Benjamin Cathcart, Priyatansh Gurha, Ali J Marian Jan 2023

Cytosolic Dna Sensing Protein Pathway Is Activated In Human Hearts With Dilated Cardiomyopathy, Leila Rouhi, Sirisha M Cheedipudi, Benjamin Cathcart, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

INTRODUCTION: The genome is constantly exposed to numerous stressors, which induce DNA lesions, including double-stranded DNA breaks (DSBs). DSBs are the most dangerous, as they induce genomic instability. In response to DNA damage, the cell activates nuclear DNA damage response (DDR) and the cytosolic DNA sensing protein (CDSP) pathways, the latter upon release of the DSBs to the cytosol. The CDSP pathway activates NFκB and IRF3, which induce the expression of the pro-inflammatory genes. There is scant data on the activation of the CDSP pathway in human hearts with dilated cardiomyopathy (DCM).

AIM: We aimed to determine expression levels of …


Exercise And Ischemia-Activated Pathways In Limb Muscle Angiogenesis And Vascular Regeneration, Vihang A Narkar Jan 2023

Exercise And Ischemia-Activated Pathways In Limb Muscle Angiogenesis And Vascular Regeneration, Vihang A Narkar

Faculty, Staff and Student Publications

Exercise has a profound effect on cardiovascular disease, particularly through vascular remodeling and regeneration. Peripheral artery disease (PAD) is one such cardiovascular condition that benefits from regular exercise or rehabilitative physical therapy in terms of slowing the progression of disease and delaying amputations. Various rodent pre-clinical studies using models of PAD and exercise have shed light on molecular pathways of vascular regeneration. Here, I review key exercise-activated signaling pathways (nuclear receptors, kinases, and hypoxia inducible factors) in the skeletal muscle that drive paracrine regenerative angiogenesis. The rationale for highlighting the skeletal muscle is that it is the largest organ recruited …


Characterizing Cellular Injury And Inflammation With Aldob-/-Mouse Model Of Mafld, Andy Rashid Jan 2023

Characterizing Cellular Injury And Inflammation With Aldob-/-Mouse Model Of Mafld, Andy Rashid

All Master's Theses

Metabolic-associated fatty liver disease (MAFLD) affects 1 in 3 people in the US and is a healthcare burden on the order of billions of dollars. MAFLD is characterized by pathological lipid accumulation in the liver, excess production of triglycerides and cholesterol, and export of LDL particles that raise serum lipid levels. These metabolic perturbations can lead to the development of liver fibrosis, chronic inflammation, and insulin resistance. Diagnosing MAFLD prior to fibrosis is crucial for successful intervention and prevention of advanced liver disease and other metabolic complications. Fructose-1Phospahte (F1P) accumulation from fructose overconsumption can drive hepatic lipogenesis and MAFLD progression. …


Neprilysin Inhibitors In Heart Failure: The Science, Mechanism Of Action, Clinical Studies, And Unanswered Questions, Biykem Bozkurt, Ajith P Nair, Arunima Misra, Claire Z Scott, Jamal H Mahar, Savitri Fedson Jan 2023

Neprilysin Inhibitors In Heart Failure: The Science, Mechanism Of Action, Clinical Studies, And Unanswered Questions, Biykem Bozkurt, Ajith P Nair, Arunima Misra, Claire Z Scott, Jamal H Mahar, Savitri Fedson

Faculty, Staff and Students Publications

This article provides a contemporary review and a new perspective on the role of neprilysin inhibition in heart failure (HF) in the context of recent clinical trials and addresses potential mechanisms and unanswered questions in certain HF patient populations. Neprilysin is an endopeptidase that cleaves a variety of peptides such as natriuretic peptides, bradykinin, adrenomedullin, substance P, angiotensin I and II, and endothelin. It has a broad role in cardiovascular, renal, pulmonary, gastrointestinal, endocrine, and neurologic functions. The combined angiotensin receptor and neprilysin inhibitor (ARNi) has been developed with an intent to increase vasodilatory natriuretic peptides and prevent counterregulatory activation …


Flecainide For Conversion And Maintenance Of Sinus Rhythm After Mitral Valve Replacement In Rheumatic Atrial Fibrillation, Umesh Tripathi, Aditya Kapoor, Surendra Kumar Agarwal, Prabhat Tewari, Shantanu Pande, Bipin Chandra, Ankit Sahu, Roopali Khanna, Sudeep Kumar, Naveen Garg, Satyendra Tewari Jan 2023

Flecainide For Conversion And Maintenance Of Sinus Rhythm After Mitral Valve Replacement In Rheumatic Atrial Fibrillation, Umesh Tripathi, Aditya Kapoor, Surendra Kumar Agarwal, Prabhat Tewari, Shantanu Pande, Bipin Chandra, Ankit Sahu, Roopali Khanna, Sudeep Kumar, Naveen Garg, Satyendra Tewari

Faculty, Staff and Student Publications

BACKGROUND: Despite successful mitral valve replacement (MVR), many patients remain in AF. Flecainide can be useful in these patients but has not been used because of underlying structural heart disease.

METHODS: We assessed oral flecainide for conversion and maintenance of SR in 25 patients of chronic rheumatic AF following MVR (age 34.4 yrs, mean AF duration: 3.6 yrs). Non-converters underwent DC cardioversion at 24 h and 4 weeks. Patients received flecainide and bb/diltiazem at discharge.

RESULTS: Single oral dose of Flecainide achieved SR in 6/25 (24%) while 19/25 achieved SR after DCC; at24 h 21/25 (84%) were in SR. With …


Cardiovascular Disease Risk Factors Among Middle-Aged And Older Adult Vietnamese American Members Of A Northern California Health Plan, Donna B Haysbert, Joan C Lo, Nirmala D Ramalingam, Nancy P Gordon Jan 2023

Cardiovascular Disease Risk Factors Among Middle-Aged And Older Adult Vietnamese American Members Of A Northern California Health Plan, Donna B Haysbert, Joan C Lo, Nirmala D Ramalingam, Nancy P Gordon

Faculty, Staff and Student Publications

OBJECTIVE: There is increasing recognition that cardiovascular disease (CVD) risk factors vary by Asian subgroups. We examined CVD risk factor prevalence among Vietnamese adults in a northern California health plan.

METHODS: We used electronic health record data to examine smoking, overweight/obesity (body mass index ≥23.0 kg/m

RESULTS: Current smoking prevalence was 20.3% for middle-aged men, 7.0% for older men, and

CONCLUSIONS: Study results suggest that more research on health conditions, lifestyle, and social factors among Vietnamese American adults is needed to develop culturally competent interventions to reduce CVD risk in this growing ethnic group.


Tnik Regulation Of Interferon Signaling And Endothelial Cell Response To Virus Infection, Khanh M Chau, Abishai Dominic, Eleanor L Davis, Sivareddy Kotla, Estefani Turcios Berrios, Arsany Fahim, Ashwin Arunesh, Shengyu Li, Dongyu Zhao, Kaifu Chen, Alan R Davis, Minh T H Nguyen, Yongxing Wang, Scott E Evans, Guangyu Wang, John P Cooke, Jun-Ichi Abe, David P Huston, Nhat-Tu Le Jan 2023

Tnik Regulation Of Interferon Signaling And Endothelial Cell Response To Virus Infection, Khanh M Chau, Abishai Dominic, Eleanor L Davis, Sivareddy Kotla, Estefani Turcios Berrios, Arsany Fahim, Ashwin Arunesh, Shengyu Li, Dongyu Zhao, Kaifu Chen, Alan R Davis, Minh T H Nguyen, Yongxing Wang, Scott E Evans, Guangyu Wang, John P Cooke, Jun-Ichi Abe, David P Huston, Nhat-Tu Le

Faculty, Staff and Student Publications

BACKGROUND: Traf2 and Nck-interacting kinase (TNIK) is known for its regulatory role in various processes within cancer cells. However, its role within endothelial cells (ECs) has remained relatively unexplored.

METHODS: Leveraging RNA-seq data and Ingenuity Pathway Analysis (IPA), we probed the potential impact of TNIK depletion on ECs.

RESULTS: Examination of RNA-seq data uncovered more than 450 Differentially Expressed Genes (DEGs) in TNIK-depleted ECs, displaying a fold change exceeding 2 with a false discovery rate (FDR) below 0.05. IPA analysis unveiled that TNIK depletion leads to the inhibition of the interferon (IFN) pathway [-log (

SUMMARY: Our findings suggest that …


The Gastrointestinal-Brain-Microbiota Axis: A Promising Therapeutic Target For Ischemic Stroke, Yan-Hao Wei, Ren-Tang Bi, Yan-Mei Qiu, Chun-Lin Zhang, Jian-Zhuang Li, Ya-Nan Li, Bo Hu Jan 2023

The Gastrointestinal-Brain-Microbiota Axis: A Promising Therapeutic Target For Ischemic Stroke, Yan-Hao Wei, Ren-Tang Bi, Yan-Mei Qiu, Chun-Lin Zhang, Jian-Zhuang Li, Ya-Nan Li, Bo Hu

Faculty, Staff and Student Publications

Ischemic stroke is a highly complex systemic disease characterized by intricate interactions between the brain and gastrointestinal tract. While our current understanding of these interactions primarily stems from experimental models, their relevance to human stroke outcomes is of considerable interest. After stroke, bidirectional communication between the brain and gastrointestinal tract initiates changes in the gastrointestinal microenvironment. These changes involve the activation of gastrointestinal immunity, disruption of the gastrointestinal barrier, and alterations in gastrointestinal microbiota. Importantly, experimental evidence suggests that these alterations facilitate the migration of gastrointestinal immune cells and cytokines across the damaged blood-brain barrier, ultimately infiltrating the ischemic brain. …


A Multicenter Cross-Sectional Study In Infants With Congenital Heart Defects Demonstrates High Diagnostic Yield Of Genetic Testing But Variable Evaluation Practices, Matthew D Durbin, Lindsey R Helvaty, Ming Li, William Border, Sara Fitzgerald-Butt, Vidu Garg, Gabrielle C Geddes, Benjamin M Helm, Seema R Lalani, Kim L Mcbride, Alexis Mcentire, Dana K Mitchell, Chaya N Murali, Stephanie B Wechsler, Benjamin J Landis, Stephanie M Ware Jan 2023

A Multicenter Cross-Sectional Study In Infants With Congenital Heart Defects Demonstrates High Diagnostic Yield Of Genetic Testing But Variable Evaluation Practices, Matthew D Durbin, Lindsey R Helvaty, Ming Li, William Border, Sara Fitzgerald-Butt, Vidu Garg, Gabrielle C Geddes, Benjamin M Helm, Seema R Lalani, Kim L Mcbride, Alexis Mcentire, Dana K Mitchell, Chaya N Murali, Stephanie B Wechsler, Benjamin J Landis, Stephanie M Ware

Faculty, Staff and Students Publications

PURPOSE: For patients with congenital heart disease (CHD), the most common birth defect, genetic evaluation is not universally accepted, and current practices are anecdotal. Here, we analyzed genetic evaluation practices across centers, determined diagnostic yield of testing, and identified phenotypic features associated with abnormal results.

METHODS: This is a multicenter cross-sectional study of 5 large children's hospitals, including 2899 children ≤14 months undergoing surgical repair for CHD from 2013 to 2016, followed by multivariate logistics regression analysis.

RESULTS: Genetic testing occurred in 1607 of 2899 patients (55%). Testing rates differed highly between institutions (42%-78%, P < .001). Choice of testing modality also differed across institutions (ie, chromosomal microarray, 26%-67%, P < .001). Genetic testing was abnormal in 702 of 1607 patients (44%), and no major phenotypic feature drove diagnostic yield. Only 849 patients were seen by geneticists (29%), ranging across centers (15%-52%, P < .001). Geneticist consultation associated with increased genetic testing yield (odds ratio: 5.7, 95% CI 4.33-7.58, P < .001).

CONCLUSION: Genetics …


Native Bk Polyomavirus Nephropathy In An Orthotopic Heart Transplant Patient, Zachary M Thompson, George Ajene, Prathit A Kulkarni, Nidhi Aggarwal, Savitri Fedson, Maulin K Shah Jan 2023

Native Bk Polyomavirus Nephropathy In An Orthotopic Heart Transplant Patient, Zachary M Thompson, George Ajene, Prathit A Kulkarni, Nidhi Aggarwal, Savitri Fedson, Maulin K Shah

Faculty, Staff and Students Publications

BK polyomavirus nephropathy (BKVN) is a common cause of nephropathy in kidney transplant patients and is typically seen within the first year after transplantation. BK polyomavirus nephropathy can occur in the native kidneys of patients with nonrenal solid-organ transplants (NRSOT). However, this is rare, especially outside the early post-transplant period, and BKVN is not usually considered in the differential diagnosis for acute kidney injury in NRSOT patients. We present a case of a 75-year-old man who had undergone orthotopic heart transplant 13 years prior with stable allograft function who developed progressive renal dysfunction in the setting of recent unilateral obstructive …


A Unified Model Of Age-Related Cardiovascular Disease, Michael Fossel, Joe Bean, Nina Khera, Mikhail G Kolonin Dec 2022

A Unified Model Of Age-Related Cardiovascular Disease, Michael Fossel, Joe Bean, Nina Khera, Mikhail G Kolonin

Faculty, Staff and Student Publications

Despite progress in biomedical technologies, cardiovascular disease remains the main cause of mortality. This is at least in part because current clinical interventions do not adequately take into account aging as a driver and are hence aimed at suboptimal targets. To achieve progress, consideration needs to be given to the role of cell aging in disease pathogenesis. We propose a model unifying the fundamental processes underlying most age-associated cardiovascular pathologies. According to this model, cell aging, leading to cell senescence, is responsible for tissue changes leading to age-related cardiovascular disease. This process, occurring due to telomerase inactivation and telomere attrition, …


Coronary Artery Calcium Score On Standard Of Care Oncologic Ct Scans For The Prediction Of Adverse Cardiovascular Events In Patients With Non-Small Cell Lung Cancer Treated With Concurrent Chemoradiotherapy, Efstratios Koutroumpakis, Ting Xu, Juan Lopez-Mattei, Tinsu Pan, Yang Lu, Jorge A Irizarry-Caro, Radhe Mohan, Xiaodong Zhang, Qing H Meng, Ruitao Lin, Tianlin Xu, Anita Deswal, Zhongxing Liao Dec 2022

Coronary Artery Calcium Score On Standard Of Care Oncologic Ct Scans For The Prediction Of Adverse Cardiovascular Events In Patients With Non-Small Cell Lung Cancer Treated With Concurrent Chemoradiotherapy, Efstratios Koutroumpakis, Ting Xu, Juan Lopez-Mattei, Tinsu Pan, Yang Lu, Jorge A Irizarry-Caro, Radhe Mohan, Xiaodong Zhang, Qing H Meng, Ruitao Lin, Tianlin Xu, Anita Deswal, Zhongxing Liao

Faculty, Staff and Student Publications

INTRODUCTION: Chemoradiotherapy (CRT) has been associated with increased incidence of cardiovascular (CV) adverse events (CVAE). Coronary artery calcium scoring (CAC) has shown to predict coronary events beyond the traditional CV risk factors. This study examines whether CAC, measured on standard of care, non-contrast chest CT (NCCT) imaging, predicts the development of CVAE in patients with non-small cell lung cancer (NSCLC) treated with CRT.

METHODS: Patients with NSCLC treated with CRT at MD Anderson Cancer Center from 7/2009 until 4/2014 and who had at least one NCCT scan within 6 months from their first CRT were identified. CAC scoring was performed …


Ankyrin Dependent Mitochondrial Function And Bioenergetics In The Heart, Janani Subramaniam, Janani Subramaniam Dec 2022

Ankyrin Dependent Mitochondrial Function And Bioenergetics In The Heart, Janani Subramaniam, Janani Subramaniam

Dissertations and Theses (Open Access)

ANK2 mutations in patients are associated with numerous arrhythmias, cardiomyopathies, and other heart defects. In the heart, AnkB, the protein encoded by ANK2, clusters relevant ion channels and cell adhesion molecules in several important domains; however, its role at Mitochondria Associated ER/SR Membranes (MAMs) has yet to be investigated. MAMs are crucial to mitochondrial function and metabolism and are signaling hubs implicated in various cardiac pathologies. Among several functions, these sites mediate the direct transfer of calcium from the ER/SR to the mitochondria to modulate ATP synthesis. Given that mitochondrial function and energy production are paramount to cardiovascular heath, …


Accuracy And Safety Of Scout Dose Resin Yttrium-90 Microspheres For Radioembolization Therapy Treatment Planning: A Prospective Single-Arm Clinical Trial, Nima Kokabi, Linzi A Webster, Mohammad Elsayed, Jeffrey M Switchenko, Bernard Chen, David Brandon, James Galt, Ila Sethi, Mircea Cristescu, S Cheenu Kappadath, David M Schuster Dec 2022

Accuracy And Safety Of Scout Dose Resin Yttrium-90 Microspheres For Radioembolization Therapy Treatment Planning: A Prospective Single-Arm Clinical Trial, Nima Kokabi, Linzi A Webster, Mohammad Elsayed, Jeffrey M Switchenko, Bernard Chen, David Brandon, James Galt, Ila Sethi, Mircea Cristescu, S Cheenu Kappadath, David M Schuster

Faculty, Staff and Student Publications

PURPOSE: To compare the accuracy and safety of 0.56 GBq resin yttrium-90 (

MATERIALS AND METHODS: This prospective single-arm clinical trial (Clinicaltrials.gov: NCT04172714) recruited patients with HCC. Patients underwent same-day mapping with MAA and scout

RESULTS: Thirty patients were treated using 19 segmental and 14 nonsegmental (ie, 2 contiguous segments or nonsegmental) therapies. MAA had weak LSF, moderate TNR, and moderate TD linear correlation with Rx

CONCLUSIONS: Compared with MAA, scout


Study Protocol Cover-All: Clinical Impact Of A Volumetric Image Method For Confirming Tumour Coverage With Ablation On Patients With Malignant Liver Lesions, Yuan-Mao Lin, Iwan Paolucci, Brian M Anderson, Caleb S O'Connor, Bastien Rigaud, Maria Briones-Dimayuga, Kyle A Jones, Kristy K Brock, Bryan M Fellman, Bruno C Odisio Dec 2022

Study Protocol Cover-All: Clinical Impact Of A Volumetric Image Method For Confirming Tumour Coverage With Ablation On Patients With Malignant Liver Lesions, Yuan-Mao Lin, Iwan Paolucci, Brian M Anderson, Caleb S O'Connor, Bastien Rigaud, Maria Briones-Dimayuga, Kyle A Jones, Kristy K Brock, Bryan M Fellman, Bruno C Odisio

Faculty, Staff and Student Publications

Purpose: This study aims to evaluate the intra-procedural use of a novel ablation confirmation (AC) method, consisting of biomechanical deformable image registration incorporating AI-based auto-segmentation, and its impact on tumor coverage by quantitative three-dimensional minimal ablative margin (MAM) CT-generated assessment.

Materials and methods: This single-center, randomized, phase II, intent-to-treat trial is enrolling 100 subjects with primary and secondary liver tumors (≤ 3 tumors, 1-5 cm in diameter) undergoing microwave or radiofrequency ablation with a goal of achieving ≥ 5 mm MAM. For the experimental arm, the proposed novel AC method is utilized for ablation applicator(s) placement verification and MAM assessment. …


Distinctive Kidney Function Trajectories Following Left Ventricular Assist Device Implantation, Carl P Walther, Julia S Benoit, Harveen K Lamba, Andrew B Civitello, Kevin F Erickson, Nandan K Mondal, Kenneth K Liao, Sankar D Navaneethan Dec 2022

Distinctive Kidney Function Trajectories Following Left Ventricular Assist Device Implantation, Carl P Walther, Julia S Benoit, Harveen K Lamba, Andrew B Civitello, Kevin F Erickson, Nandan K Mondal, Kenneth K Liao, Sankar D Navaneethan

Faculty, Staff and Students Publications

BACKGROUND: The aim of this study was to assess for distinct kidney function trajectories following left ventricular assist device (LVAD) placement. Cohort studies of LVAD recipients demonstrate that kidney function tends to increase early after LVAD placement, followed by decline and limited sustained improvement. Inter-individual differences in kidney function response may be obscured.

METHODS: We identified continuous flow LVAD implantations in US adults (2016-2017) from INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). Primary outcomes were estimated glomerular filtration rate (eGFR) trajectories pre-implantation to ∼12 months. Latent class mixed models were applied to primary and validation samples. Clinical differences among …