Cardiology Commons^™

Clopidogrel Versus Aspirin Monotherapy Following Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: An Updated Meta- Analysis Of 162,829 Patients, Mohammed A. Elbahloul, Ahmed Mansour, Amr Galal, Walaa M. Moawad, Manar Khaled, Ahmed Wahdan Kasem, Eman E. Labeeb, Islam Y. Elgendy

Gill Heart & Vascular Institute Faculty Publications

Background: Dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) remains a cornerstone for preventing ischemic events; however, the optimal long-term single antiplatelet therapy after completion of DAPT remains unclear. We aimed to compare clopidogrel and aspirin monotherapy after completion of the standard duration of DAPT.

Methods: A systematic search was conducted on PubMed, Scopus, Cochrane Library, and Web of Science from inception to April 2025. We included randomized clinical trials and observational studies that compared aspirin versus clopidogrel monotherapy after completion of standard-duration DAPT. The primary and co-primary outcomes were major adverse cardiovascular events (MACE) and major bleeding, respectively. …

Colchicine Among Patients With Acute Coronary Syndrome: A Meta‑Analysis Of Randomized Trials, Mohamed Hamed, Sheref A. Mohamed, Mohamed Abdelazeem, Eric Lieberman, Abdelrahman Ali, Dharam J. Kumbhani, Anthony Bavry, Hani Jneid, Islam Y. Elgendy, Ayman Elbadawi

Gill Heart & Vascular Institute Faculty Publications

Introduction: Prior trials evaluating the benefit of colchicine in patients with acute coronary syndrome (ACS) have yielded mixed results. Hence, we conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the role of colchicine after ACS.

Methods: We performed an electronic search of MEDLINE, Embase, and Cochrane databases through November 2024 for studies comparing colchicine with placebo after ACS. Our study’s primary outcome was major adverse cardiac events (MACE).

Results: Our final analysis included five RCTs with 12,979 patients with a mean follow-up of 26.6 months. The weighted mean age was 59.8 years. Colchicine was associated with a modest …

A Unified Finite Element Framework For Cardiac Growth And Remodeling In Mitral Regurgitation Incorporating Fiber Reorientation And Baroreflex, Mohammad Mehri, Jonathan F. Wenk

Mechanical Engineering Faculty Publications

Mitral regurgitation (MR) triggers complex cardiac remodeling responses that alter the structure and function of the left ventricle (LV). While several models have been developed to predict myocardial growth in MR, they often neglect key concurrent adaptive mechanisms that influence both the pattern and severity of LV dilation. This study presents a unified finite element framework to systematically evaluate the individual and combined contributions of fiber reorientation (FR) and baroreflex regulation to LV growth and remodeling, along with the effects of myocardial material property changes associated with the acute and chronic phases of MR. A healthy baseline model and multiple …

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 …

Synergistic Effects Of Plasma S100b And Mri Measures Of Cerebrovascular Disease On Cognition In Older Adults, Colleen A. Pappas, Christopher E. Bauer, Valentinos Zachariou, Timothy Justin Libecap, Beatriz Rodolpho, Tiffany L. Sudduth, Peter T. Nelson, Gregory Jicha, Anika M. S. Hartz, Xingfeng Shao, Danny J. J. Wang, Brian T. Gold

Neurology Faculty Publications

There is growing interest in studying vascular contributions to cognitive impairment and dementia (VCID) and developing biomarkers to identify at-risk individuals. A combination of biofluid and neuroimaging markers may better profile early stage VCID than individual measures. Here, we tested this possibility focusing on plasma levels of S100 calcium-binding protein B (S100B), which has been linked with blood– brain-barrier (BBB) integrity, and neuroimaging measures assessing BBB function (water exchange rate across the BBB (kw)) and cerebral small vessel disease (white matter hyperintensities (WMHs)). A total of 74 older adults without dementia had plasma samples collected and underwent cognitive assessment. A …

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

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

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, …

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

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

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.)

Health Literacy And Perceived Control: Intermediary Factors In The Relationship Between Race And Cardiovascular Disease Risk In Incarcerated Men In The United States, Jennifer L. Miller, Misook L. Chung, Lovoria B. Williams, Alison R. Connell, Zyad T. Saleh, Abdullah S. Alhurani, Alison L. Bailey, Mary Kay Rayens, Debra K. Moser

UK CARES Faculty Publications

Background: Black race, inadequate health literacy, and poor perceived control are predictors of increased cardiovascular disease (CVD) risk. The purpose of this study was to explore the relationships among race, health literacy, perceived control, and CVD risk while controlling for known risk factors in incarcerated men. Methods: We included data from 349 incarcerated men to examine race and CVD risk (Framingham Risk Score) using a serial mediation model with health literacy and perceived control using 95% confidence intervals (CIs) from 5000 bootstrap samples. Results: Of the participants (age, 36 ± 10; education, 12 ± 2; body mass index, 28.3 ± …

Cerebrovascular Disease Is Associated With Alzheimer's Plasma Biomarker Concentrations In Adults With Down Syndrome, Andreas Engvig, Karl Trygve Kalleberg, Lars T. Westlye, Esten Høyland Leonardsen, Alzheimer’S Disease Neuroimaging Initiative Consortium

Neurology Faculty Publications

DNA methylation age (MA), brain age (BA), and frailty index (FI) are putative aging biomarkers linked to dementia risk. We investigated their relationship and combined potential for prediction of cognitive impairment and future dementia risk using the ADNI database. Of several MA algorithms, DunedinPACE and GrimAge2, associated with memory, were combined in a composite MA alongside BA and a data-driven FI in predictive analyses. Pairwise correlations between age- and sex-adjusted measures for MA (aMA), aBA, and aFI were low. FI outperformed BA and MA in all diagnostic tasks. A model including age, sex, and aFI achieved an area under the …

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 …

Depressive Symptoms And Sleep Quality Mediate The Relationship Between Race And Quality Of Life Among Patients With Heart Failure: A Serial Multiple Mediator Model, Jia-Rong Wu, Debra K. Moser, Chin-Yen Lin, Ambrose A. Chiang, Barbara Riegel

UK CARES Faculty Publications

Background: Black patients with heart failure (HF) report worse quality of life (QoL) than White patients. Few investigators have examined mediators of the association between race and QoL, but depressive symptoms and sleep quality are associated with QoL.

Objective: The aim of this study was to determine whether depressive symptoms and sleep quality are mediators of the relationship between race and QoL among patients with HF.

Methods: This was a cross-sectional study. We included 271 outpatients with HF. Self-reported race (White/Black), depressive symptoms (Patient Health Questionnaire), sleep quality (Pittsburgh Sleep Quality Index), and QoL (Kansas City Cardiomyopathy Questionnaire) were collected …

Patient Denial Of Myocardial Infarction In The Prehospital Phase: Prevalence And Correlates, Mona A. Abed, Amani A. Khalil, Debra K. Moser

UK CARES Faculty Publications

Background: Limited knowledge exists regarding patients' denial of myocardial infarction (MI) before hospitalization for an MI. Objective: The aim of this study was to determine the prevalence and correlates of denial of MI in the prehospital phase of a confirmed MI. Methods: This secondary analysis included 166 hospitalized patients (mean [SD] age, 54.1 [10.5] years) who developed MI outside a healthcare facility and had high congruence between their experienced and expected symptoms. Measurements included the Denial subscale of the Brief COPE Inventory, the modified Response to Symptoms Questionnaire, and a Likert scale measuring perceived risk for MI. Patients who arrived …

Insights Into The Influence Of Income Variability On Cardiovascular Risk In Non-Elderly Adults With Type 2 Diabetes, Ketrell Mcwhorter

UK CARES Faculty Publications

No abstract provided.

Androgen Aggravates Aortic Aneurysms Via Suppression Of Pd-1 In Mice, Xufang Mu, Shu Liu, Zhuoran Wang, Kai Jiang, Timothy S. Mcclintock, Arnold Stromberg, Alejandro V. Tezanos, Eugene S. Lee, John A. Curci, Ming C. Gong, Zhenheng Guo

Markey Cancer Center Faculty Publications

Androgen has long been recognized for its pivotal role in the sexual dimorphism of cardiovascular diseases, including aortic aneurysms (AAs), a devastating vascular disease with a higher prevalence and fatality rate in men than in women. However, the mechanism by which androgen mediates AAs is largely unknown. Here, we found that male, not female, mice developed AAs when exposed to aldosterone and high salt (Aldo-salt). We revealed that androgen and androgen receptors (ARs) were crucial for this sexually dimorphic response to Aldo-salt. We identified programmed cell death protein 1 (PD-1), an immune checkpoint, as a key link between androgen and …

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

Saha Cardiovascular Research Center Faculty Publications

No abstract provided.

National Trends Of Vascular Risk Factor Control Among Stroke Survivors: From The National Health And Nutrition Examination Survey 2009 To 2020, Hend Mansoor, Daniel Manion, Kara Jo Swafford, Gregory A. Jicha, Daniela Claudia Moga

Neurology Faculty Publications

BACKGROUND: Contemporary data describing the national trends on vascular risk factor control among stroke survivors are limited.

METHODS AND RESULTS: This is a cross-sectional analysis of the National Health and Nutrition Examination Survey cycles 2009 to 2010 to 2017 to March 2020. Adults (≥18 years of age) with a self-reported diagnosis of stroke were identified. Age- adjusted trends in hypertension, diabetes, and hyperlipidemia control were examined. Sex and racial differences in vascular risk factor control were also investigated. Among 32 497 adult individuals who participated in the National Health and Nutrition Examination Survey, 1354 participants (4.2%) self-reported a prior diagnosis …

Astrocytic Mitochondrial Transfer To Brain Endothelial Cells And Pericytes In Vivo Increases With Aging, Gopal V. Velmurugan, Hemendra J. Vekaria, Samir P. Patel, Patrick G. Sullivan, W. Brad Hubbard

Neurology Faculty Publications

Intercellular mitochondrial transfer (IMT) is an intriguing biological phenomenon where mitochondria are transferred between different cells and notably, cell types. IMT is physiological, occurring in normal conditions, but also is utilized to deliver healthy mitochondria to cells in distress. Transferred mitochondria can be integrated to improve cellular metabolism, and mitochondrial function. Research on the mitochondrial transfer axis between astrocytes and brain capillaries in vivo is limited by the cellular heterogeneity of the neurovascular unit. To this end, we developed an inducible mouse model that expresses mitochondrial Dendra2 only in astrocytes and then isolated brain capillaries to remove all intact astrocytes. …

Using Digital Pathology To Analyze The Murine Cerebrovasculature, Dana M. Niedowicz, Jenna L. Gollihue, Erica M. Weekman, Panhavuth Phe, Donna M. Wilcock, Christopher M. Norris, Peter T. Nelson

Neurology Faculty Publications

Research on the cerebrovasculature may provide insights into brain health and disease. Immunohistochemical staining is one way to visualize blood vessels, and digital pathology has the potential to revolutionize the measurement of blood vessel parameters. These tools provide opportunities for translational mouse model research. However, mouse brain tissue presents a formidable set of technical challenges, including potentially high background staining and crossreactivity of endogenous IgG. Formalin-fixed paraffin-embedded (FFPE) and fixed frozen sections, both of which are widely used, may require different methods. In this study, we optimized blood vessel staining in mouse brain tissue, testing both FFPE and frozen fixed …

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 …

Neurotensin Accelerates Atherosclerosis And Increases Circulating Levels Of Short-Chain And Saturated Triglycerides, Jing Li, Liping Yang, Jun Song, Baoxiang Yan, Andrew J. Morris, Hunter Moseley, Robert M. Flight, Chi Wang, Jinpeng Liu, Heidi L. Weiss, Edward F. Morris, Ilyes Abdelhamid, Mathias J. Gerl, Olle Melander, Susan Smyth, B. Mark Evers

Markey Cancer Center Faculty Publications

Background and aims: Obesity and type 2 diabetes are significant risk factors for atherosclerotic cardiovascular disease (CVD) worldwide, but the underlying pathophysiological links are poorly understood. Neurotensin (NT), a 13-amino-acid hormone peptide, facilitates intestinal fat absorption and contributes to obesity in mice fed a high-fat diet. Elevated levels of pro-NT (a stable NT precursor produced in equimolar amounts relative to NT) are associated with obesity, type 2 diabetes, and CVD in humans. Whether NT is a causative factor in CVD is unknown.

Methods: Nt+/+ and Nt–/– mice were either injected with adeno-associated virus encoding PCSK9 mutants or crossed with Ldlr–/– …

Mediation By Fatalism Of The Association Between Symptom Burden And Self-Care Management In Patients With Heart Failure, Ashmita Thapa, Misook L. Chung, Jia-Rong Wu, Abigail Latimer, Terry A. Lennie, Gia Mudd-Martin, Chin-Yen Lin, Jessica Harman Thompson, Junghee Kang, Debra K. Moser

UK CARES Faculty Publications

Background: Clinicians and researchers often assume that symptom burden is associated with self-care management (SCM) in patients with heart failure (HF). However, that association is often not borne out in simple regression analyses and may be because another variable mediates the association. Fatalism is an appropriate candidate for mediation and is the belief that circumstances are predetermined without opportunity for control by individuals.

Objective: Our objective was to determine whether fatalism mediated the relationship of symptom burden with SCM among adults with HF.

Methods: We conducted a secondary analysis (N = 95) from a clinical trial. We used Self-care of …

Mediators Of The Association Between Cognitive Function And Self-Care Behaviors In Patients Hospitalized With An Exacerbation Of Heart Failure, Jia-Rong Wu, Chin-Yen Lin, Abigail Latimer, Muna Hassan Hammash, Debra K. Moser

UK CARES Faculty Publications

Background: Patients with heart failure (HF) must engage in self-care, yet their self-care is often poor. Cognitive function commonly is impaired in HF and is associated with poor self-care. Heart failure knowledge and self-care confidence also are needed to preform self-care. Few investigators have examined mediators of the association of cognitive function with self-care.

Objectives: The aim of this study was to determine whether HF knowledge and self-care confidence mediated the association of cognitive function with self-care maintenance and management among patients with HF.

Methods: This was a cross-sectional observational study of 164 patients with HF. Cognitive function was assessed …

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

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

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 …