Cardiology Commons^™

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 …

Semi-Automated Construction Of Patient-Specific Aortic Valves From Computed Tomography Images, Dan Lior, Charles Puelz, Colin Edwards, Silvana Molossi, Boyce E Griffith, Ravi K Birla, Craig G Rusin

Faculty, Staff and Students Publications

This paper presents a semi-automatic method for the construction of volumetric models of the aortic valve using computed tomography angiography images. Although the aortic valve typically cannot be segmented directly from a computed tomography angiography image, the method described herein uses manually selected samples of an aortic segmentation derived from this image to inform the construction. These samples capture certain physiologic landmarks and are used to construct a volumetric valve model. As a demonstration of the capabilities of this method, valve models for 25 pediatric patients are created. A selected valve anatomy is used to perform fluid-structure interaction simulations using …

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 …

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

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.

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

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 …

Discovery And Systematic Characterization Of Risk Variants And Genes For Coronary Artery Disease In Over A Million Participants, Krishna G Aragam, Tao Jiang, Anuj Goel, Stavroula Kanoni, Brooke N Wolford, Deepak S Atri, Elle M Weeks, Minxian Wang, George Hindy, Wei Zhou, Christopher Grace, Carolina Roselli, Nicholas A Marston, Frederick K Kamanu, Ida Surakka, Loreto Muñoz Venegas, Paul Sherliker, Satoshi Koyama, Kazuyoshi Ishigaki, Bjørn O Åsvold, Michael R Brown, Ben Brumpton, Paul S De Vries, Olga Giannakopoulou, Panagiota Giardoglou, Daniel F Gudbjartsson, Ulrich Güldener, Syed M Ijlal Haider, Anna Helgadottir, Maysson Ibrahim, Adnan Kastrati, Thorsten Kessler, Theodosios Kyriakou, Tomasz Konopka, Ling Li, Lijiang Ma, Thomas Meitinger, Sören Mucha, Matthias Munz, Federico Murgia, Jonas B Nielsen, Markus M Nöthen, Shichao Pang, Tobias Reinberger, Gavin Schnitzler, Damian Smedley, Gudmar Thorleifsson, Moritz Von Scheidt, Jacob C Ulirsch, Biobank Japan, Epic-Cvd, David O Arnar, Noël P Burtt, Maria C Costanzo, Jason Flannick, Kaoru Ito, Dong-Keun Jang, Yoichiro Kamatani, Amit V Khera, Issei Komuro, Iftikhar J Kullo, Luca A Lotta, Christopher P Nelson, Robert Roberts, Gudmundur Thorgeirsson, Unnur Thorsteinsdottir, Thomas R Webb, Aris Baras, Johan L M Björkegren, Eric Boerwinkle, George Dedoussis, Hilma Holm, Kristian Hveem, Olle Melander, Alanna C Morrison, Marju Orho-Melander, Loukianos S Rallidis, Arno Ruusalepp, Marc S Sabatine, Kari Stefansson, Pierre Zalloua, Patrick T Ellinor, Martin Farrall, John Danesh, Christian T Ruff, Hilary K Finucane, Jemma C Hopewell, Robert Clarke, Rajat M Gupta, Jeanette Erdmann, Nilesh J Samani, Heribert Schunkert, Hugh Watkins, Cristen J Willer, Panos Deloukas, Sekar Kathiresan, Adam S Butterworth, Cardiogramplusc4d Consortium

Faculty, Staff and Student Publications

The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in …

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. …

Polygenic Risk Score Improves The Accuracy Of A Clinical Risk Score For Coronary Artery Disease, Austin King, Lang Wu, Hong-Wen Deng, Hui Shen, Chong Wu

Faculty, Staff and Student Publications

BACKGROUND: The value of polygenic risk scores (PRSs) towards improving guideline-recommended clinical risk models for coronary artery disease (CAD) prediction is controversial. Here we examine whether an integrated polygenic risk score improves the prediction of CAD beyond pooled cohort equations. METHODS: An observation study of 291,305 unrelated White British UK Biobank participants enrolled from 2006 to 2010 was conducted. A case-control sample of 9499 prevalent CAD cases and an equal number of randomly selected controls was used for tuning and integrating of the polygenic risk scores. A separate cohort of 272,307 individuals (with follow-up to 2020) was used to examine …

Radiation Therapy Induces Immunosenescence Mediated By P90rsk, Masaki Imanishi, Haizi Cheng, Sivareddy Kotla, Anita Deswal, Nhat-Tu Le, Eduardo Chini, Kyung Ae Ko, Venkata S K Samanthapudi, Ling-Ling Lee, Joerg Herrmann, Xiaolei Xu, Cielito Reyes-Gibby, Sai-Ching J Yeung, Keri L Schadler, Syed Wamique Yusuf, Zhongxing Liao, Roza Nurieva, El-Ad David Amir, Jared K Burks, Nicolas L Palaskas, John P Cooke, Steven H Lin, Michihiro Kobayashi, Momoko Yoshimoto, Jun-Ichi Abe

Faculty, Staff and Student Publications

Radiation therapy (RT) to the chest increases the patients’ risk of cardiovascular disease (CVD). A complete understanding of the mechanisms by which RT induces CVD could lead to specific preventive, therapeutic approaches. It is becoming evident that both genotoxic chemotherapy agents and radiation induce mitochondrial dysfunction and cellular senescence. Notably, one of the common phenotypes observed in cancer survivors is accelerated senescence, and immunosenescence is closely related to both cancer risk and CVD development. Therefore, suppression of immunosenescence can be an ideal target to prevent cancer treatment-induced CVD. However, the mechanism(s) by which cancer treatments induce immunosenescence are incompletely characterized. …

Cardiovascular Outcomes In Patients With Chronic Kidney Disease And Covid-19: A Multi-Regional Data-Linkage Study, Emilie J Lambourg, Peter J Gallacher, Robert W Hunter, Moneeza Siddiqui, Eve Miller-Hodges, James D Chalmers, Dan Pugh, Neeraj Dhaun, Samira Bell

Faculty, Staff and Student Publications

BACKGROUND: Data describing cardiovascular outcomes in patients with coronavirus disease 2019 (COVID-19) and chronic kidney disease (CKD) are lacking. We compared cardiovascular outcomes of patients with and without COVID-19, stratified by CKD status.

METHODS: This retrospective, multi-regional data-linkage study utilised individual patient-level data from two Scottish cohorts. All patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Cohort 1 between 1 February 2020 and 31 March 2021 and in Cohort 2 between 28 February 2020 and 8 February 2021 were included.

RESULTS: Overall, 86 964 patients were tested for SARS-CoV-2. There were 36 904 patients (mean±sd age 61±21 …

Rad Regulation Of Cav12 Channels Controls Cardiac Fight-Or-Flight Response, Arianne Papa, Sergey I Zakharov, Alexander N Katchman, Jared S Kushner, Bi-Xing Chen, Lin Yang, Guoxia Liu, Alejandro Sanchez Jimenez, Robyn J Eisert, Gary A Bradshaw, Wen Dun, Shah R Ali, Aaron Rodriques, Karen Zhou, Veli Topkara, Mu Yang, John P Morrow, Emily J Tsai, Arthur Karlin, Elaine Wan, Marian Kalocsay, Geoffrey S Pitt, Henry M Colecraft, Manu Ben-Johny, Steven O Marx

Faculty, Staff and Student Publications

Fight-or-flight responses involve β-adrenergic-induced increases in heart rate and contractile force. In the present study, we uncover the primary mechanism underlying the heart's innate contractile reserve. We show that four protein kinase A (PKA)-phosphorylated residues in Rad, a calcium channel inhibitor, are crucial for controlling basal calcium current and essential for β-adrenergic augmentation of calcium influx in cardiomyocytes. Even with intact PKA signaling to other proteins modulating calcium handling, preventing adrenergic activation of calcium channels in Rad-phosphosite-mutant mice (4SA-Rad) has profound physiological effects: reduced heart rate with increased pauses, reduced basal contractility, near-complete attenuation of β-adrenergic contractile response and diminished …

Impact Of Social Determinants Of Health On Anticoagulant Use Among Patients With Atrial Fibrillation: Systemic Review And Meta-Analysis, Rasha Khatib, Nicole Glowacki, John Byrne, Peter Brady

Faculty, Staff and Student Publications

BACKGROUND: A growing body of literature now exists examining associations between social determinants of health (SDOH) and adverse outcomes in patients with atrial fibrillation; however, little is available on anticoagulant prescriptions and the impact of SDOH.

PURPOSE: Evaluate the impact of SDOH on anticoagulant prescriptions in patients with atrial fibrillation.

DATA SOURCES: Medline and Embase databases up to January 2021.

STUDY SELECTION: Noninterventional studies were included if they reported associations between at least 1 of 14 SDOH domains and anticoagulant prescription in patients with atrial fibrillation. Two investigators independently screened and collected data.

DATA EXTRACTION: Two investigators independently screened and …

Polygenic Risk, Midlife Life's Simple 7, And Lifetime Risk Of Stroke, Emy A Thomas, Nitesh Enduru, Adrienne Tin, Eric Boerwinkle, Michael E Griswold, Thomas H Mosley, Rebecca F Gottesman, Myriam Fornage

Faculty, Staff and Student Publications

Background

Recent genetic discoveries in stroke have unleashed the potential of using genetic information for risk prediction and health interventions aimed at disease prevention. We sought to estimate the lifetime risk of stroke (LTRS) by levels of genetic risk and to investigate whether optimal cardiovascular health can offset the negative impact of high genetic risk on lifetime risk of stroke.

Methods and Results

Study participants were 11 568 middle‐aged adults (56% women, 23% Black adults), who were free of stroke at baseline and were followed up for a median of 28 years. The remaining LTRS was estimated according to levels …

Association Of Cardiovascular Health Through Young Adulthood With Genome-Wide Dna Methylation Patterns In Midlife: The Cardia Study, Yinan Zheng, Brian T Joyce, Shih-Jen Hwang, Jiantao Ma, Lei Liu, Norrina B Allen, Amy E Krefman, Jun Wang, Tao Gao, Drew R Nannini, Haixiang Zhang, David R Jacobs, Myron D Gross, Myriam Fornage, Cora E Lewis, Pamela J Schreiner, Stephen Sidney, Dongquan Chen, Philip Greenland, Daniel Levy, Lifang Hou, Donald M Lloyd-Jones

Faculty, Staff and Student Publications

Background: Cardiovascular health (CVH) from young adulthood is strongly associated with an individual's future risk of cardiovascular disease (CVD) and total mortality. Defining epigenomic biomarkers of lifelong CVH exposure and understanding their roles in CVD development may help develop preventive and therapeutic strategies for CVD.

Methods: In 1085 CARDIA study (Coronary Artery Risk Development in Young Adults) participants, we defined a clinical cumulative CVH score that combines body mass index, blood pressure, total cholesterol, and fasting glucose measured longitudinally from young adulthood through middle age over 20 years (mean age, 25-45). Blood DNA methylation at >840 000 methylation markers was …

Free Cholesterol Bioavailability And Atherosclerosis, Rei J Abe, Jun-Ichi Abe, Minh T H Nguyen, Elizabeth A Olmsted-Davis, Abrar Mamun, Priyanka Banerjee, John P Cooke, Longhou Fang, Henry Pownall, Nhat-Tu Le

Faculty, Staff and Student Publications

Purpose of review: As both a cholesterol acceptor and carrier in the reverse cholesterol transport (RCT) pathway, high-density lipoprotein (HDL) is putatively atheroprotective. However, current pharmacological therapies to increase plasma HDL cholesterol (HDL-c) concentration have paradoxically failed to prevent or reduce atherosclerosis and cardiovascular disease (CVD). Given that free cholesterol (FC) transfer between surfaces of lipoproteins and cells is reversible, excess plasma FC can be transferred to the cells of peripheral tissue sites resulting in atherosclerosis. Here, we summarize potential mechanisms contributing to this paradox and highlight the role of excess free cholesterol (FC) bioavailability in atherosclerosis vs. atheroprotection.

Recent …

Quantification Of Infarct Core Signal Using Ct Imaging In Acute Ischemic Stroke, Uma Maria Lal-Trehan Estrada, Grant Meeks, Sergio Salazar-Marioni, Fabien Scalzo, Mudassir Farooqui, Juan Vivanco-Suarez, Santiago Ortega Gutierrez, Sunil A Sheth, Luca Giancardo

Faculty, Staff and Student Publications

In stroke care, the extent of irreversible brain injury, termed infarct core, plays a key role in determining eligibility for acute treatments, such as intravenous thrombolysis and endovascular reperfusion therapies. Many of the pivotal randomized clinical trials testing those therapies used MRI Diffusion-Weighted Imaging (DWI) or CT Perfusion (CTP) to define infarct core. Unfortunately, these modalities are not available 24/7 outside of large stroke centers. As such, there is a need for accurate infarct core determination using faster and more widely available imaging modalities including Non-Contrast CT (NCCT) and CT Angiography (CTA). Prior studies have suggested that CTA provides improved …

Complexities And Complications Of Extreme Obesity, Haval Ali, Udit Naik, Michelle Mcdonald, Mohammad Almosa, Karen Horn, Alexis Staines, Louis Maximilian Buja

Faculty, Staff and Student Publications

Obesity is a common chronic disorder and has detrimental long-term consequences if left untreated. Herein, we report a case of a young lady who suffered from morbid obesity and many of its consequences, and we present a literature review of these complications. While the cause of obesity is multifactorial, the genetic component is particularly important in the pathophysiology of marked obesity. Resistance to Leptin is considered one of the main causes of obesity. There is a unique relationship between polycystic ovary syndrome and obesity, as observed in our case. Obesity is associated with cardiovascular and lung diseases such as heart …

Magi1 Inhibits Interferon Signaling To Promote Influenza A Infection, Yin Wang, Jun-Ichi Abe, Khanh M Chau, Yongxing Wang, Hang Thi Vu, Loka Reddy Velatooru, Fahad Gulraiz, Masaki Imanishi, Venkata S K Samanthapudi, Minh T H Nguyen, Kyung Ae Ko, Ling-Ling Lee, Tamlyn N Thomas, Elizabeth A Olmsted-Davis, Sivareddy Kotla, Keigi Fujiwara, John P Cooke, Di Zhao, Scott E Evans, Nhat-Tu Le

Faculty, Staff and Student Publications

We have shown that membrane-associated guanylate kinase with inverted domain structure-1 (MAGI1), a scaffold protein with six PSD95/DiscLarge/ZO-1 (PDZ) domains, is involved in the regulation of endothelial cell (EC) activation and atherogenesis in mice. In addition to causing acute respiratory disease, influenza A virus (IAV) infection plays an important role in atherogenesis and triggers acute coronary syndromes and fatal myocardial infarction. Therefore, the aim of this study is to investigate the function and regulation of MAGI1 in IAV-induced EC activation. Whereas, EC infection by IAV increases MAGI1 expression, MAGI1 depletion suppresses IAV infection, suggesting that the induction of MAGI1 may …

Cancer Treatment-Induced Nad+ Depletion In Premature Senescence And Late Cardiovascular Complications, Priyanka Banerjee, Elizabeth A Olmsted-Davis, Anita Deswal, Minh Th Nguyen, Efstratios Koutroumpakis, Nicholas L Palaskas, Steven H Lin, Sivareddy Kotla, Cielito Reyes-Gibby, Sai-Ching J Yeung, Syed Wamique Yusuf, Momoko Yoshimoto, Michihiro Kobayashi, Bing Yu, Keri Schadler, Joerg Herrmann, John P Cooke, Abhishek Jain, Eduardo Chini, Nhat-Tu Le, Jun-Ichi Abe

Faculty, Staff and Student Publications

Numerous studies have revealed the critical role of premature senescence induced by various cancer treatment modalities in the pathogenesis of aging-related diseases. Senescence-associated secretory phenotype (SASP) can be induced by telomere dysfunction. Telomeric DNA damage response induced by some cancer treatments can persist for months, possibly accounting for long-term sequelae of cancer treatments. Telomeric DNA damage-induced mitochondrial dysfunction and increased reactive oxygen species production are hallmarks of premature senescence. Recently, we reported that the nucleus-mitochondria positive feedback loop formed by p90 ribosomal S6 kinase (p90RSK) and phosphorylation of S496 on ERK5 (a unique member of the mitogen-activated protein kinase family …

Effects Of Tamoxifen Inducible Mercremer On Gene Expression In Cardiac Myocytes In Mice, Leila Rouhi, Siyang Fan, Sirisha M Cheedipudi, Melis Olcum, Hyun-Hwan Jeong, Zhongming Zhao, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

The Cre-LoxP technology, including the tamoxifen (TAM) inducible MerCreMer (MCM), is increasingly used to delineate gene function, understand the disease mechanisms, and test therapeutic interventions. We set to determine the effects of TAM-MCM on cardiac myocyte transcriptome. Expression of the MCM was induced specifically in cardiac myocytes upon injection of TAM to myosin heavy chain 6-MCM (Myh6-Mcm) mice for 5 consecutive days. Cardiac function, myocardial histology, and gene expression (RNA-sequencing) were analyzed 2 weeks after TAM injection. A total of 346 protein coding genes (168 up- and 178 down-regulated) were differentially expressed. Transcript levels of 85 genes, analyzed …

The Wnt/Β-Catenin Pathway Regulates Expression Of The Genes Involved In Cell Cycle Progression And Mitochondrial Oxidative Phosphorylation In The Postmitotic Cardiac Myocytes, Melis Olcum, Sirisha M Cheedipudi, Leila Rouhi, Siyang Fan, Hyun-Hwan Jeong, Zhongming Zhao, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

INTRODUCTION: Aging is associated with cardiac myocyte loss, sarcopenia, and cardiac dysfunction. Adult cardiac myocytes are postmitotic cells with an insufficient proliferative capacity to compensate for myocyte loss. The canonical WNT (cWNT) pathway is involved in the regulation of cell cycle reentry in various cell types. The effects of the cWNT pathway on the expression of genes involved in cell cycle reentry in the postmitotic cardiac myocytes are unknown.

AIM: The aim of the study was to identify genes whose expression is regulated by the β-catenin, the indispensable component to the cWNT signaling, in the postmitotic myocytes.

METHODS AND RESULTS: …

Serum Gamma Glutamyltransferase (Ggt) In Coronary Artery Disease: Exploring The Asian Indian Connection, Kunal K Singh, Aditya Kapoor, Roopali Khanna, Ankit Sahu, Vishwas Kapoor, Sudeep Kumar, Naveen Garg, Satyendra Tewari, Pravin Goel

Faculty, Staff and Student Publications

BACKGROUND: There is a need to identify novel markers for CAD, independent of traditional CV risk factors. One of these is gamma-glutamyl transferase (GGT), a marker of increased oxidative stress. Given the high prevalence of CAD in Asian Indians, the link of GGT and CAD in them needs to be studied.

AIM: To assess GGT in patients with angiographically documented CAD.

METHODS AND RESULTS: Two hundred patients aged 58.1 ± 9.95 years, 73% males, hypertension 56%, diabetes 40% were included. Mean GGT was 63.6 ± 44.33 (10–269 U/L). The levels of GGT progressively increased in those with single/double or triple-vessel …

Soluble Angiotensin-Converting Enzyme 2, Cardiac Biomarkers, Structure, And Function, And Cardiovascular Events (From The Atherosclerosis Risk In Communities Study), Aliza Hussain, Olive Tang, Caroline Sun, Xiaoming Jia, Elizabeth Selvin, Vijay Nambi, Aaron Folsom, Gerardo Heiss, Faiez Zannad, Thomas Mosley, Salim S Virani, Josef Coresh, Eric Boerwinkle, Bing Yu, Jonathan W Cunningham, Amil M Shah, Scott D Solomon, James A De Lemos, Ron C Hoogeveen, Christie M Ballantyne

Faculty, Staff and Students Publications

Membrane-bound angiotensin-converting enzyme 2 is important in regulation of the renin-angiotensin-aldosterone system, but the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) is unclear. We evaluated the association of sACE2 with cardiac biomarkers, structure, and function and cardiovascular events in the Atherosclerosis Risk in Communities Study. sACE2 was measured in a subset of 497 participants (mean age 78±5.4 years, 53% men, 27% black); Cox regression analyses assessed prospective associations of sACE2 with time to first CVD event at median 6.1-year follow-up. sACE2 was higher in men, blacks, and participants with prevalent CVD, diabetes, or hypertension. Higher sACE2 levels …

Continuous-Flow Left Ventricular Assist Device Therapy In Adults With Transposition Of The Great Vessels, Tadahisa Sugiura, Chitaru Kurihara, Masashi Kawabori, Andre C Critsinelis, Andrew B Civitello, Jeffrey A Morgan, O H Frazier

Faculty, Staff and Students Publications

An increasing number of children with congenital heart disease are surviving into adulthood and subsequently developing end-stage heart failure. Two example populations are adults who have been previously operated on for congenitally corrected transposition of the great arteries (CCTGA) and transposition of the great arteries (TGA). Implantation of a continuous flow left ventricular assist device (CF-LVAD) in these patients can present unusual anatomical and physiologic challenges. In this report, we describe outcomes of CF-LVAD implantation in three such patients. These cases demonstrate the feasibility of implanting a CF-LVAD in patients who have undergone surgery for CCTGA and/or TGA.

Tortuosity-Powered Microfluidic Device For Assessment Of Thrombosis And Antithrombotic Therapy In Whole Blood, David J Luna, Navaneeth K R Pandian, Tanmay Mathur, Justin Bui, Pranav Gadangi, Vadim V Kostousov, Shiu-Ki Rocky Hui, Jun Teruya, Abhishek Jain

Faculty, Staff and Students Publications

Accurate assessment of blood thrombosis and antithrombotic therapy is essential for the management of patients in a variety of clinical conditions, including surgery and on extracorporeal life support. However, current monitoring devices do not measure the effects of hemodynamic forces that contribute significantly to coagulation, platelet function and fibrin formation. This limits the extent to which current assays can predict clotting status in patients. Here, we demonstrate that a biomimetic microfluidic device consisting stenosed and tortuous arteriolar vessels would analyze blood clotting under flow, while requiring a small blood volume. When the device is connected to an inline pressure sensor …