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Circulatory and Respiratory Physiology

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Full-Text Articles in Cardiology

Extracorporeal Rescue In Massive Pulmonary Embolism: A Case Of Chronic Thromboembolic Pulmonary Hypertension Unveiled, Kenzo Ramos, Kari Gorder Jul 2026

Extracorporeal Rescue In Massive Pulmonary Embolism: A Case Of Chronic Thromboembolic Pulmonary Hypertension Unveiled, Kenzo Ramos, Kari Gorder

Journal of Shock and Hemodynamics

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare yet curable cause of pulmonary hypertension from unresolved pulmonary emboli. We present the case of a 48-year-old man with progressive dyspnea and leg swelling, who was found to have bilateral pulmonary emboli with right heart strain. He developed cardiac arrest during thrombectomy, requiring emergent veno-arterial extracorporeal membrane oxygenation (V-A ECMO). Further evaluation revealed acute emboli superimposed on CTEPH. After incomplete thrombectomy and persistent instability, he underwent successful pulmonary endarterectomy with ECMO decannulation, leading to recovery of right ventricular function and discharge in stable condition. This case illustrates that previously unrecognized CTEPH may …


Prognostic Value Of Baseline Qfr In Single-Vessel Intermediate Coronary Stenosis, Yanfeng Lu, Abdulrahman Alqazzaz, Jasmine Bao, Gary S. Mintz, Jiahao Feng, Yong Zhang, Shanshan Gao, Qiang Song, Feifei Ning, Xin Huang, Ning Guo Jan 2026

Prognostic Value Of Baseline Qfr In Single-Vessel Intermediate Coronary Stenosis, Yanfeng Lu, Abdulrahman Alqazzaz, Jasmine Bao, Gary S. Mintz, Jiahao Feng, Yong Zhang, Shanshan Gao, Qiang Song, Feifei Ning, Xin Huang, Ning Guo

Student Papers, Posters & Projects

BACKGROUND AND OBJECTIVES: The prognostic value of baseline Quantitative Flow Ratio (QFR) in real-world patients remains unclear. This study aimed to evaluate the prognostic value of baseline QFR and its three-tier model-low, grey-zone, and high QFR-in patients with single-vessel intermediate stenosis.

METHODS: This retrospective study included 478 patients with QFR between 0.70 and 0.90 who underwent coronary angiography between May and June 2023. Patients were stratified into Low (0.70-0.74), Grey-Zone (0.75-0.85), and High (0.86-0.90) QFR groups. The primary endpoint was major adverse cardiac events (MACE); the key secondary endpoint was target vessel failure (TVF). Kaplan-Meier and Cox proportional hazards models …


Animal Models Of Aortic Aneurysm And Dissection: A Comparative Guide For Mechanism, Therapeutic Testing, And Translational Readouts, Shayan Mohammadmoradi, Sidney W. Whiteheart Jan 2026

Animal Models Of Aortic Aneurysm And Dissection: A Comparative Guide For Mechanism, Therapeutic Testing, And Translational Readouts, Shayan Mohammadmoradi, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Aortic aneurysms and dissections are devastating vascular diseases with high mortality, yet no pharmacological therapy has proven effective in halting growth or preventing rupture. Surgical and endovascular repair remain the only treatment options for advanced disease. Animal models have been indispensable in defining mechanisms and testing candidate therapies, but the diversity of protocols, strain-dependent variability, and heterogeneous endpoints complicate interpretation and translation. This review provides an update focused on how to match models to specific research questions. We critically compare commonly used abdominal aortic aneurysm (AAA) models (angiotensin II ± hyperlipidemia, elastase, calcium chloride, β-aminopropionitrile BAPN hybrids, and mineralocorticoid agonist/fludrocortisone …


A Review Of Recent And Developing Studies Regarding Percutaneous Coronary Intervention (Pci): A Narrative Review, Bisher Alsabbagh, Azeez Shala, Joshua Rupert, Abdallah Elsayed Dec 2025

A Review Of Recent And Developing Studies Regarding Percutaneous Coronary Intervention (Pci): A Narrative Review, Bisher Alsabbagh, Azeez Shala, Joshua Rupert, Abdallah Elsayed

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Biology)

This comprehensive literature review synthesizes the most recent evidence and evolving clinical guidelines concerning percutaneous coronary intervention (PCI) from 2015 to 2025. The study integrates findings from 42 peer-reviewed trials, meta-analyses, registries, and international guideline statements issued by the American College of Cardiology/American Heart Association (ACC/AHA), European Society of Cardiology (ESC), and related societies. Results reveal a decade-long evolution in PCI practice marked by a shift from anatomy-driven to physiology and imaging-guided decision-making, supported by tools such as fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), intravascular ultrasound (IVUS), and optical coherence tomography (OCT). Modern guidelines emphasize individualized, team-based revascularization …


Development Of A Longitudinal, Small-Group Pocus Curriculum For Internal Medicine Residents, Shah N. Mahmud Do, Ammar W. Bhatti Do, Ariq Rahman Md, Omar Al Qassab Md, Fraser Mackay Md Nov 2025

Development Of A Longitudinal, Small-Group Pocus Curriculum For Internal Medicine Residents, Shah N. Mahmud Do, Ammar W. Bhatti Do, Ariq Rahman Md, Omar Al Qassab Md, Fraser Mackay Md

The Lahey Journal

Development of a Longitudinal, Small-Group POCUS Curriculum for Internal Medicine Residents

Introduction

Point-of-Care Ultrasound (POCUS) is integral for clinicians to enhance their diagnostic and procedural skills. Unlike Emergency Medicine or Anesthesia training programs, Internal Medicine programs often lack a structured and standardized curriculum. We thus developed a longitudinal and multi-pronged POCUS curriculum aimed at building trainee competency when utilizing ultrasound for diagnostic and procedural work-up.

Methods

The curriculum encompasses the following: basics of ultrasound, ultrasound-guided procedures, thoracic ultrasound/Bed Lung Ultrasound in Emergency (BLUE), and cardiac ultrasound/Focus-Assessed Transthoracic Echocardiography (FATE). These modules were integrated into the residents’ clinic blocks. We utilized …


Orthostatic Hypotension In Older Adults And Its Economic Impact On The Healthcare System: A Systematic Literature Review, Olushola E. Ilogho, Jennifer Broyles, Viet Le, Denise Rizzolo Oct 2025

Orthostatic Hypotension In Older Adults And Its Economic Impact On The Healthcare System: A Systematic Literature Review, Olushola E. Ilogho, Jennifer Broyles, Viet Le, Denise Rizzolo

Lynchburg Journal of Medical Science

ABSTRACT

Orthostatic Hypotension (OH) has been shown to lead to poor quality of life, falls, and death. Literature suggests that falls from OH may be preventable, therefore opportunities to reduce its associated cost to the healthcare system exist. This literature review aims to evaluate the importance of diagnosing and treating OH in older adult patients. OH is the drop in blood pressure upon changing to an upright position. This acute hemodynamic drop in blood pressure causes hypoperfusion in the brain, leading to dizziness, syncope, and falls. An extensive literature search for publications in PubMed and Cumulative Index in Nursing and …


Association Of Estimated Plasma Volume Status With Invasive Hemodynamics And Adverse Clinical Outcomes In Patients With Pulmonary Hypertension And Chronic Kidney Disease, Andrew Geller, Jose Manuel Martinez Manzano, Esteban Kosak Lopez, Phuuwadith Wattanachayakul, John Malin, Raul Leguizamon, Tara John, Rasha Khan, Ian Mclaren, Alexander Prendergast, Simone Jarrett, Kevin Bryan Lo, Christian Witzke Sep 2025

Association Of Estimated Plasma Volume Status With Invasive Hemodynamics And Adverse Clinical Outcomes In Patients With Pulmonary Hypertension And Chronic Kidney Disease, Andrew Geller, Jose Manuel Martinez Manzano, Esteban Kosak Lopez, Phuuwadith Wattanachayakul, John Malin, Raul Leguizamon, Tara John, Rasha Khan, Ian Mclaren, Alexander Prendergast, Simone Jarrett, Kevin Bryan Lo, Christian Witzke

Einstein Health Papers

Identifying noninvasive measures to assess intravascular volume status and risk stratify patients with pulmonary hypertension (PH) and chronic kidney disease (CKD) is needed. We assessed the predictive value of estimated plasma volume status (ePVS) using the Strauss-derived Duarte formula in PH-CKD patients. This single-center retrospective cohort analysis included patients with PH and CKD Stage 3b (CKD3b), Stage 4 (CKD4), or Stage 5 (CKD5) who underwent right heart catheterization from 2018 to 2023. Patients were categorized into low ePVS (< 6.2) and high ePVS (≥ 6.2) using Youden's J statistics. We used the Cox-proportional hazards model, adjusting for age, sex, and body mass index, to investigate the association between …


Bilateral Pulmonary Embolism With Bi-Atrial Cardiac Thrombi Entrapped In A Patent Foramen Ovale, Denise Mourad, Fahd Eissa Mohamed, Yashi Ballal, Elie Mrad, Natasa Petreska, Sachin Singh, Paritharsh Ghantasala Sep 2025

Bilateral Pulmonary Embolism With Bi-Atrial Cardiac Thrombi Entrapped In A Patent Foramen Ovale, Denise Mourad, Fahd Eissa Mohamed, Yashi Ballal, Elie Mrad, Natasa Petreska, Sachin Singh, Paritharsh Ghantasala

Journal of Community Hospital Internal Medicine Perspectives

Bi-atrial thrombi with bilateral pulmonary embolism (PE) through a patent foramen ovale (PFO) is rare and life-threatening, requiring urgent management due to embolization risk. We present a 53-year-old female with left lower extremity extensive deep vein thrombosis (DVT), bilateral PE, and bi-atrial thrombi straddling a PFO. She underwent thrombectomy, PFO closure, and pulmonary embolectomy but later experienced recurrent DVT and PE. Anticoagulation was limited due to bleeding risk given a recent neurosurgery. Literature lacks clear guidelines for managing such cases necessitating individualized treatment. This case highlights the complexity of bi-atrial thrombi with PFO and the need for further research to …


Using Atrial Pacing Trials After Tavr To Assess Conduction Abnormalities And Predict Need For Pacemaker Implantation, Hemish M. Philip, Matthew R. Summers, Shirish R. Yasa, Hasani Amir, Daiwik P. Munjwani, Thomas A. Cook, Matthew G. Jackson Aug 2025

Using Atrial Pacing Trials After Tavr To Assess Conduction Abnormalities And Predict Need For Pacemaker Implantation, Hemish M. Philip, Matthew R. Summers, Shirish R. Yasa, Hasani Amir, Daiwik P. Munjwani, Thomas A. Cook, Matthew G. Jackson

Cardiovascular Research Symposium

Abstract:

Background: Transcatheter Aortic Valve Replacement (TAVR) is the standard of care for many patients with severe aortic stenosis who cannot undergo surgical intervention. However, conduction disturbances remain a frequent complication, particularly with self-expanding valves. This often leads to permanent pacemaker implantation (PPI). At Sentara Heart Hospital, atrial pacing at 140 bpm is standard practice during TAVR to assess AV conduction.

Objective: This study aims to evaluate whether preserved 1:1 atrioventricular (AV) conduction during routine atrial pacing at 140 bpm after self-expanding TAVR predicts a low likelihood of requiring PPI, thus yielding a high negative predictive value (NPV).

Methods: We …


Development Of Overt Hypo-Attenuated Leaflet Thickening Following Transcatheter Aortic Valve Replacement, Stephonda Lewis, Hemish M. Philip, Matthew Summers Aug 2025

Development Of Overt Hypo-Attenuated Leaflet Thickening Following Transcatheter Aortic Valve Replacement, Stephonda Lewis, Hemish M. Philip, Matthew Summers

Cardiovascular Research Symposium

Background: Transcatheter aortic valve replacement (TAVR) is a cornerstone therapy for severe aortic stenosis. Up to one-third of patients develop hypoattenuated leaflet thickening (HALT) within the first year post-TAVR. HALT, a form of leaflet thrombosis, can progress to leaflet immobility and structural deterioration. Despite its significance, no unified approach exists for screening or management of HALT after TAVR.

Case Presentation: A 64-year-old woman presented with shortness of breath on exertion. Exam revealed a 3/6 systolic murmur, and echocardiogram confirmed severe aortic stenosis. She underwent TAVR with resolution of symptoms and was discharged on clopidogrel (Plavix) as single antiplatelet therapy. Two …


Effectiveness Of Glucagon-Like Peptide 1 Receptor Agonists In The Treatment Of Heart Failure, Lisa Kristen Schloemann Aug 2025

Effectiveness Of Glucagon-Like Peptide 1 Receptor Agonists In The Treatment Of Heart Failure, Lisa Kristen Schloemann

SIU Journal of Medical Science Scholarly Works

ABSTRACT

Purpose: The purpose of this article is to review the use of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in heart failure (HF) treatment considering the HF phenotype and comorbidities, including type 2 diabetes mellitus (DM) and obesity.

Method: A PubMed and Google Scholar literature search was conducted with search terms, HF and GLP-1 RA. Seven pertinent articles were retrieved and served as the basis for this clinical review.

Results: The efficacy of GLP-1 RA therapy in patients with heart failure with reduced ejection fractions (HFrEF) is unclear, with one study showing increased adverse cardiac events including tachyarrhythmias, and …


A Case Of A Massive Right Atrial Thrombus Removal Under Transesophageal Echocardiographic Guidance, Justin Phillips, Max Kabolowsky, Alex M. Hendon, Samantha Arzillo Apr 2025

A Case Of A Massive Right Atrial Thrombus Removal Under Transesophageal Echocardiographic Guidance, Justin Phillips, Max Kabolowsky, Alex M. Hendon, Samantha Arzillo

HCA Healthcare Journal of Medicine

Background

With the advent of catheter guided interventions, practitioners have added another tool alongside chemical lysis and surgical removal to reduce the clot burden of patients with large emboli and thrombi. Due to comorbid conditions, many patients are poor candidates for surgical or chemical clot treatment but may present optimally for catheter-based thromboembolectomy. In this case, we highlight the benefits of mechanical thrombectomy with transesophageal echocardiographic guidance to reduce the clot burden of a patient who would otherwise be considered a poor candidate for surgical or chemical treatment.

Case Presentation

This case follows a 78-year-old man with a past medical …


Maternal Health And Congenital Heart Defects: Investigating Ventricular Septal Defects In South Texas Region 11, Miguel A. Lopez, Sophia Moon, Jonathan M. Hebert, Padmanabhan Rengasamy Mar 2025

Maternal Health And Congenital Heart Defects: Investigating Ventricular Septal Defects In South Texas Region 11, Miguel A. Lopez, Sophia Moon, Jonathan M. Hebert, Padmanabhan Rengasamy

Research Symposium

Congenital heart defects are a known risk factor for early childhood mortality and can be traced to poor maternal health, a crisis plaguing the South Texas region. This perspective research project utilizes previously computed data on the prevalence of ventricular septal defects (VSD) in South Texas region 11 combined with a comprehensive literature review to investigate the correlation between both maternal obesity and diabetes with VSD. Current literature supports a significant association between maternal diabetes and VSD, with one Russian study reporting an eight to nine fold increased risk in VSD in children born to diabetic mothers. By contrast, the …


Biochemical And Biophysical Properties Of Failing Myocardium In Rare Patient Populations, Gregory Nathaniel Milburn Jan 2025

Biochemical And Biophysical Properties Of Failing Myocardium In Rare Patient Populations, Gregory Nathaniel Milburn

Theses and Dissertations--Physiology

Heart failure has diverse underlying etiologies, complicating research. While some types, like ischemic disease or inherited mutations, are well-studied, research on rarer forms has lagged. Understanding the molecular drivers in these populations may enhance diagnostics and therapies. This work examines two rare groups: patients with ATTR cardiac amyloidosis and those receiving mechanical assist device support. We show that myocardium from patients with amyloidosis has increased fibrosis and reduced force production without changes in cross-bridge kinetics. Additionally, we show that the passive stiffness of amyloidosis myocardium is not different from non-failing myocardium, indicating increased ventricular wall thickness may cause restrictive filling. …


Serglycin Controls Megakaryocyte Retention Of Platelet Factor 4 And Influences Megakaryocyte Fate In Bone Marrow, Joshua Lykins, Isabelle C. Becker, Virginia Camacho, Hammodah Rawhi Hammodah Alfar, Joonwoo Park, Joseph Italiano, Sidney W. Whiteheart Jan 2025

Serglycin Controls Megakaryocyte Retention Of Platelet Factor 4 And Influences Megakaryocyte Fate In Bone Marrow, Joshua Lykins, Isabelle C. Becker, Virginia Camacho, Hammodah Rawhi Hammodah Alfar, Joonwoo Park, Joseph Italiano, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Megakaryocytes (MKs) produce platelets, and similar to other hematopoietic progenitors, they are involved in homeostatic aspects of their bone marrow niche. MKs release and endocytose various factors, such as platelet factor 4 (PF4)/CXCL4. Here, we show that the intra-α-granular proteoglycan, serglycin (SRGN), plays a key role in this process by retaining PF4, and perhaps other factors, during MK maturation. Immature, SRGN–/– MKs released ~80% of their PF4, and conditioned media from these cells negatively affected wild-type MK differentiation in vitro. This was replicated in wild-type MKs by treatment with the polycation surfen, a known inhibitor of glycosaminoglycan (GAG)/protein interactions. In …


Abcg5/Abcg8-Independent Mechanisms Fail To Maintain Sterol Balance In Mice Fed A High-Cholesterol Diet, Garrett B. Anspach, Rupinder Kaur, Isha Chauhan, Erika L. Savage, Brittney Poole, Victoria P. Noffsinger, Xiaoming Fu, Zeneng Wang, Clairity Voy, Ryan E. Temel, Scott M. Gordon, Robert N. Helsley, Gregory A. Graf Jan 2025

Abcg5/Abcg8-Independent Mechanisms Fail To Maintain Sterol Balance In Mice Fed A High-Cholesterol Diet, Garrett B. Anspach, Rupinder Kaur, Isha Chauhan, Erika L. Savage, Brittney Poole, Victoria P. Noffsinger, Xiaoming Fu, Zeneng Wang, Clairity Voy, Ryan E. Temel, Scott M. Gordon, Robert N. Helsley, Gregory A. Graf

Saha Cardiovascular Research Center Faculty Publications

The ABCG5/ABCG8 (G5G8) sterol transporter opposes the accumulation of dietary xenosterols but is also the primary mediator of biliary cholesterol secretion. In humans and in mouse models of disrupted biliary cholesterol secretion, fecal neutral sterols (FNSs) remain constant, indicating the presence of an alternate pathway for cholesterol excretion. Transintestinal cholesterol elimination or excretion (TICE) is thought to compensate for biliary disruptions and G5G8 insufficiency. We sought to measure the compensatory increase in intestinal cholesterol secretion and provide mechanistic insight for how TICE maintains sterol balance in the absence of hepatic G5G8. Differences were not observed in FNSs between control, acute, …


Venous Thromboembolism Prophylaxis In Orthopedic Surgery: A Narrative Review, Jacob Lahti, Sarah Gallitto, Thomas C. Varkey Dec 2024

Venous Thromboembolism Prophylaxis In Orthopedic Surgery: A Narrative Review, Jacob Lahti, Sarah Gallitto, Thomas C. Varkey

Annual Research Symposium

This poster highlights current and updated guidelines for chemical and mechanical prophylaxis for venous thromboembolism in patients undergoing major and minor orthopedic surgery. Existing and new potential therapies were reviewed, as well as an analysis into the lack of high-quality risk-prediction score calculators to improve personalization of prophylaxis regimens. Alongside a summary of existing and potential new prophylaxis protocols, a call to action to improve validity of said risk score calculators so as to improve patient outcomes and personalized medicine is made.


Apoa2 Increases Cholesterol Efflux Capacity To Plasma Hdl By Displacing The C-Terminus Of Resident Apoa1, Snigdha Sarkar, Jamie Morris, Youngki You, Hannah Sexmith, Scott E. Street, Stephanie M. Thibert, Isaac K. Attah, Chelsea M. Hutchinson Bunch, Irina V. Novikova, James E. Evans, Amy S. Shah, Scott M. Gordon, Jere P. Segrest, Karin E. Bornfeldt, Tomas Vaisar, Jay W. Heinecke, W. Sean Davidson, John T. Melchior Dec 2024

Apoa2 Increases Cholesterol Efflux Capacity To Plasma Hdl By Displacing The C-Terminus Of Resident Apoa1, Snigdha Sarkar, Jamie Morris, Youngki You, Hannah Sexmith, Scott E. Street, Stephanie M. Thibert, Isaac K. Attah, Chelsea M. Hutchinson Bunch, Irina V. Novikova, James E. Evans, Amy S. Shah, Scott M. Gordon, Jere P. Segrest, Karin E. Bornfeldt, Tomas Vaisar, Jay W. Heinecke, W. Sean Davidson, John T. Melchior

Saha Cardiovascular Research Center Faculty Publications

Abstract The ability of high-density lipoprotein (HDL) to promote cellular cholesterol efflux is a more robust predictor of cardiovascular disease protection than HDL-cholesterol levels in plasma. Previously, we found that lipidated HDL containing both apolipoprotein A-I (APOA1) and A-II (APOA2) promotes cholesterol efflux via the ATP-binding cassette transporter (ABCA1). In the current study, we directly added purified, lipid-free APOA2 to human plasma and found a dose-dependent increase in whole plasma cholesterol efflux capacity. APOA2 likewise increased the cholesterol efflux capacity of isolated HDL with the maximum effect occurring when equal masses of APOA1 and APOA2 coexisted on the particles. Follow-up …


Untargeted Lipidomics Reveals Novel Hdl Metabotypes And Lipid-Clinical Correlates, Peer W. F. Karmaus, Scott M. Gordon, Marcus Y. Chen, Alison A. Motsinger-Reif, Rodney W. Snyder, Timothy R. Fennell, Suramya Waidyanatha, Reshan A. Fernando, Alan T. Remaley, Michael B. Fessler Dec 2024

Untargeted Lipidomics Reveals Novel Hdl Metabotypes And Lipid-Clinical Correlates, Peer W. F. Karmaus, Scott M. Gordon, Marcus Y. Chen, Alison A. Motsinger-Reif, Rodney W. Snyder, Timothy R. Fennell, Suramya Waidyanatha, Reshan A. Fernando, Alan T. Remaley, Michael B. Fessler

Saha Cardiovascular Research Center Faculty Publications

Plasma high-density lipoprotein (HDL), originally studied for its role in lipid transport, is now appreciated to have wide-ranging biological functions that become defective during disease. While >200 lipids have collectively been detected in HDL, published HDL lipidomic analyses in different diseases have commonly been targeted to prespecified subsets of lipids. Here, we report the results of untargeted lipidomic analysis of HDL isolated from 101 subjects referred for computed tomographic coronary imaging for whom multiple additional clinical and lipoprotein metadata were measured. Unsupervised clustering of the total HDL lipidome revealed that the subjects fell into one of two discrete groups, herein …


Tissue Plasminogen Activator Associated Pulmonary Hemorrhage In Patient With Acta2-Associated Arteriopathy, Travis G. Hughes, Mark A. Wurth, Mary Burchett Sheppard Dec 2024

Tissue Plasminogen Activator Associated Pulmonary Hemorrhage In Patient With Acta2-Associated Arteriopathy, Travis G. Hughes, Mark A. Wurth, Mary Burchett Sheppard

Saha Cardiovascular Research Center Faculty Publications

Pulmonary hemorrhage after administration of tissue plasminogen activator (tPA) is a rare complication. We present a 15- year-old boy with a heterozygous pathogenic variant in ACTA2 who presented with right brachial artery aneurysm thrombosis treated initially with tPA, resulting in pulmonary hemorrhage. We hypothesize that the underlying pulmonary abnormalities caused by the pathogenic ACTA2 variant may be a risk factor for pulmonary hemorrhage after tPA administration. (J Vasc Surg Cases Innov Tech 2024;10:101558.)


Enhancement Of High-Density Lipoprotein-Associated Protease Inhibitor Activity Prevents Atherosclerosis Progression, Maura Mobilia, Alexander A. Karakashian, Khaga R. Neupane, Olivia Hage, Callie Whitus, Abigail Carter, Clairity Voy, Lance A. Johnson, Gregory A. Graf, Scott M. Gordon Sep 2024

Enhancement Of High-Density Lipoprotein-Associated Protease Inhibitor Activity Prevents Atherosclerosis Progression, Maura Mobilia, Alexander A. Karakashian, Khaga R. Neupane, Olivia Hage, Callie Whitus, Abigail Carter, Clairity Voy, Lance A. Johnson, Gregory A. Graf, Scott M. Gordon

Saha Cardiovascular Research Center Faculty Publications

Background and aims: Inflammatory cells within atherosclerotic lesions secrete proteolytic enzymes that contribute to lesion progression and destabilization, increasing the risk for an acute cardiovascular event. Elastase is a serine protease, secreted by macrophages and neutrophils, that may contribute to the development of unstable plaque. We previously reported interaction of endogenous protease-inhibitor proteins with high- density lipoprotein (HDL), including alpha-1-antitrypsin, an inhibitor of elastase. These findings support a potential role for HDL as a modulator of protease activity. In this study, we test the hypothesis that enhancement of HDL-associated elastase inhibitor activity is protective against atherosclerotic lesion progression.

Methods: We …


Antisense Oligonucleotide Targeting Hepatic Serum Amyloid A Limits The Progression Of Angiotensin Ii-Induced Abdominal Aortic Aneurysm Formation, Preetha Shridas, Ailing Ji, Andrea C. Trumbauer, Victoria P. Noffsinger, Luke W. Meredith, Frederick C. De Beer, Adam E. Mullick, Nancy R. Webb, Dennis G. Karounos, Lisa R. Tannock Apr 2024

Antisense Oligonucleotide Targeting Hepatic Serum Amyloid A Limits The Progression Of Angiotensin Ii-Induced Abdominal Aortic Aneurysm Formation, Preetha Shridas, Ailing Ji, Andrea C. Trumbauer, Victoria P. Noffsinger, Luke W. Meredith, Frederick C. De Beer, Adam E. Mullick, Nancy R. Webb, Dennis G. Karounos, Lisa R. Tannock

Saha Cardiovascular Research Center Faculty Publications

Background and aims: Obesity increases the risk for abdominal aortic aneurysms (AAA) in humans and enhances angiotensin II (AngII)-induced AAA formation in C57BL/6 mice. We reported that deficiency of Serum Amyloid A (SAA) significantly reduces AngII-induced inflammation and AAA in both hyperlipidemic apoE-deficient and obese C57BL/6 mice. The aim of this study is to investigate whether SAA plays a role in the progression of early AAA in obese C57BL/6 mice.

Methods: Male C57BL/6J mice were fed a high-fat diet (60% kcal as fat) throughout the study. After 4 months of diet, the mice were infused with AngII until the end …


Abdominal Aortic Aneurysms And Platelets: Infiltration, Inflammation, And Elastin Disintegration, Bowen Li, Hong S. Lu, Alan Daugherty Mar 2024

Abdominal Aortic Aneurysms And Platelets: Infiltration, Inflammation, And Elastin Disintegration, Bowen Li, Hong S. Lu, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

No abstract provided.


Common Heart Failure With Preserved Ejection Fraction Animal Models Yield Disparate Myofibril Mechanics, Axel J. Fenwick, Vivek P. Jani, D. Brian Foster, Thomas E. Sharp, Traci T. Goodchild, Kyle Lapenna, Jake E. Doiron, David J. Lefer, Joseph A. Hill, David A. Kass, Anthony Cammarato Jan 2024

Common Heart Failure With Preserved Ejection Fraction Animal Models Yield Disparate Myofibril Mechanics, Axel J. Fenwick, Vivek P. Jani, D. Brian Foster, Thomas E. Sharp, Traci T. Goodchild, Kyle Lapenna, Jake E. Doiron, David J. Lefer, Joseph A. Hill, David A. Kass, Anthony Cammarato

School of Medicine Faculty Publications

No abstract provided.


Inflammation And Tumor Progression: The Differential Impact Of Saa In Breast Cancer Models, Daniel Wilhelm Olivier, Carla Eksteen, Manisha Du Plessis, Louis De Jager, Lize Engelbrecht, Nathaniel Wade Mcgregor, Preetha Shridas, Frederick C. De Beer, Willem J. S. De Villiers, Etheresia Pretorius, Anna-Mart Engelbrecht Jan 2024

Inflammation And Tumor Progression: The Differential Impact Of Saa In Breast Cancer Models, Daniel Wilhelm Olivier, Carla Eksteen, Manisha Du Plessis, Louis De Jager, Lize Engelbrecht, Nathaniel Wade Mcgregor, Preetha Shridas, Frederick C. De Beer, Willem J. S. De Villiers, Etheresia Pretorius, Anna-Mart Engelbrecht

Saha Cardiovascular Research Center Faculty Publications

Background: Previous research has shown that the Serum Amyloid A (SAA) protein family is intricately involved in inflammatory signaling and various disease pathologies. We have previously demonstrated that SAA is associated with increased colitis disease severity and the promotion of tumorigenesis. However, the specific role of SAA proteins in breast cancer pathology remains unclear. Therefore, we investigated the role of systemic SAA1 and SAA2 (SAA1/2) in a triple-negative breast cancer mouse model.

Methods: Syngeneic breast tumors were established in wild-type mice, and mice lacking the SAA1/2 (SAADKO). Subsequently, tumor volume was monitored, species survival determined, the inflammatory profiles of mice …


Deficiency Of Acute-Phase Serum Amyloid A Exacerbates Sepsis-Induced Mortality And Lung Injury In Mice, Ailing Ji, Andrea C. Trumbauer, Victoria P. Noffsinger, Luke W. Meredith, Brittany Dong, Qian Wang, Ling Guo, Xiangan Li, Frederick C. De Beer, Nancy R. Webb, Lisa R. Tannock, Marlene E. Starr, Christopher M. Waters, Preetha Shridas Dec 2023

Deficiency Of Acute-Phase Serum Amyloid A Exacerbates Sepsis-Induced Mortality And Lung Injury In Mice, Ailing Ji, Andrea C. Trumbauer, Victoria P. Noffsinger, Luke W. Meredith, Brittany Dong, Qian Wang, Ling Guo, Xiangan Li, Frederick C. De Beer, Nancy R. Webb, Lisa R. Tannock, Marlene E. Starr, Christopher M. Waters, Preetha Shridas

Saha Cardiovascular Research Center Faculty Publications

Serum amyloid A (SAA) is a family of proteins, the plasma levels of which may increase >1000-fold in acute inflammatory states. We investigated the role of SAA in sepsis using mice deficient in all three acute-phase SAA isoforms (SAA-TKO). SAA deficiency significantly increased mortality rates in the three experimental sepsis mouse models: cecal ligation and puncture (CLP), cecal slurry (CS) injection, and lipopolysaccharide (LPS) treatments. SAA-TKO mice had exacerbated lung pathology compared to wild-type (WT) mice after CLP. A bulk RNA sequencing performed on lung tissues excised 24 h after CLP indicated significant enrichment in the expression of genes associated …


Ecohiv-Infected Mice Show No Signs Of Platelet Activation, Hammodah Rawhi Hammodah Alfar, Dominic Ngima Nthenge-Ngumbau, Kathryn E. Saatman, Sidney W. Whiteheart Dec 2023

Ecohiv-Infected Mice Show No Signs Of Platelet Activation, Hammodah Rawhi Hammodah Alfar, Dominic Ngima Nthenge-Ngumbau, Kathryn E. Saatman, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Platelets express several surface receptors that could interact with different viruses. To understand the mechanisms of HIV-1′s interaction with platelets, we chose the EcoHIV model. While EcoHIV is an established model for neuroAIDS, its effects on platelets are ill-defined. Our results indicate that EcoHIV behaves differently from HIV-1 and is cleared from circulation after 48 h post- infection. The EcoHIV course of infection resembles an HIV-1 infection under the effects of combined antiretroviral therapy (cART) since infected mice stayed immunocompetent and the virus was readily detected in the spleen. EcoHIV-infected mice failed to become thrombocytopenic and showed no signs of …


Loss Of Carnitine Palmitoyltransferase 1a Reduces Docosahexaenoic Acid-Containing Phospholipids And Drives Sexually Dimorphic Liver Disease In Mice, Mikala M. Zelows, Corissa Cady, Nikitha Dharanipragada, Anna E. Mead, Zachary A. Kipp, Evelyn A. Bates, Venkateshwari Varadharajan, Rakhee Banerjee, Se-Hyung Park, Nathan R. Shelman, Harrison A. Clarke, Tara R. Hawkinson, Terrymar Medina, Ramon C. Sun, Todd A. Lydic, Terry D. Hinds, Jr., J. Mark Brown, Samir Softic, Gregory A. Graf, Robert N. Helsley Dec 2023

Loss Of Carnitine Palmitoyltransferase 1a Reduces Docosahexaenoic Acid-Containing Phospholipids And Drives Sexually Dimorphic Liver Disease In Mice, Mikala M. Zelows, Corissa Cady, Nikitha Dharanipragada, Anna E. Mead, Zachary A. Kipp, Evelyn A. Bates, Venkateshwari Varadharajan, Rakhee Banerjee, Se-Hyung Park, Nathan R. Shelman, Harrison A. Clarke, Tara R. Hawkinson, Terrymar Medina, Ramon C. Sun, Todd A. Lydic, Terry D. Hinds, Jr., J. Mark Brown, Samir Softic, Gregory A. Graf, Robert N. Helsley

Saha Cardiovascular Research Center Faculty Publications

Background and aims: Genome and epigenome wide association studies identified variants in carnitine palmitoyltransferase 1a (CPT1a) that associate with lipid traits. The goal of this study was to determine the role of liver-specific CPT1a on hepatic lipid metabolism.

Approach and results: Male and female liver-specific knockout (LKO) and littermate controls were placed on a low-fat or high-fat diet (60% kcal fat) for 15 weeks. Mice were necropsied after a 16 h fast, and tissues were collected for lipidomics, matrix-assisted laser desorption ionization mass spectrometry imaging, kinome analysis, RNA-sequencing, and protein expression by immunoblotting. Female LKO mice had increased serum alanine …


Α-Synuclein Is The Major Platelet Isoform But Is Dispensable For Activation, Secretion, And Thrombosis, Alexis N. Smith, Smita Joshi, Harry Chanzu, Hammodah Rawhi Hammodah Alfar, Kanakanagavalli Shravani Prakhya, Sidney W. Whiteheart Nov 2023

Α-Synuclein Is The Major Platelet Isoform But Is Dispensable For Activation, Secretion, And Thrombosis, Alexis N. Smith, Smita Joshi, Harry Chanzu, Hammodah Rawhi Hammodah Alfar, Kanakanagavalli Shravani Prakhya, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Platelets play many roles in the vasculature ensuring proper hemostasis and maintaining integrity. These roles are facilitated, in part, by cargo molecules released from platelet granules via Soluble NSF Attachment Protein Receptor (SNARE) mediated membrane fusion, which is controlled by several protein-protein interactions. Chaperones have been characterized for t-SNAREs (i.e. Munc18b for Syntaxin-11), but none have been clearly identified for v-SNAREs. α- Synuclein has been proposed as a v-SNARE chaperone which may affect SNARE-complex assembly, fusion pore opening, and thus secretion. Despite its abundance and that it is the only isoform present, α-synuclein’s role in platelet secretion is uncharacterized. In …


Coronary Artery Calcium Scoring In Asymptomatic Patients, Bilal Hussain, Ahmed Mahmood, Michael G. Flynn, Thomas Alexander Oct 2023

Coronary Artery Calcium Scoring In Asymptomatic Patients, Bilal Hussain, Ahmed Mahmood, Michael G. Flynn, Thomas Alexander

HCA Healthcare Journal of Medicine

Coronary artery calcium (CAC) scoring is an important prognostic tool for personalized cardiovascular preventive care and has recently been incorporated into American College of Cardiology/American Heart Association guidelines. CAC provides direct visualization and quantification of CAC burden for risk stratification and primary prevention of cardiovascular events in an asymptomatic population. CAC scoring is recommended for individuals with intermediate 10-year atherosclerotic cardiovascular disease (ASCVD) risk and selective populations with borderline ASCVD risk. In this review, we outline the interpretation of CAC scores for predicting the risk of cardiovascular events, and we highlight the guidelines for starting statin and potentially starting aspirin …