Cardiovascular Diseases Commons^™

Mechanism-Driven Therapy For Diabetic Cardiovascular Disease, Fabian Sanchis-Gomar, Carl J. Lavie, Salvatore Carbone, Ian J. Neeland

EVMS School of Health Professions Faculty Publications

[Introduction] Diabetic cardiovascular disease is a network disorder, not a glucose-only complication

Diabetes accelerates cardiovascular (CV) target-organ damage through multiple interacting biological modules that amplify risk even when glycemia is modestly controlled^[1]. These modules include (i) adipose tissue dysfunction with altered adipokine secretion and immune-cell infiltration; (ii) ectopic lipid deposition in liver, myocardium, and perivascular/epicardial fat (iii) endothelial dysfunction with impaired nitric oxide bioavailability and heightened oxidative stress (iv) chronic kidney disease (CKD)-mediated volume, pressure, and uremic-toxin stress, and (v) autonomic and neurohormonal activation that promotes hypertension, arrhythmias, and remodeling^[1]. The clinical spectrum includes macrovascular disease …

Ultra-Processed Foods And The Cardiovascular-Kidney-Metabolic Continuum: Integrating Epidemiological, Multi-Omics, And Translational Evidence, Saiful Singar, Amirhossein Ataei Kachouei, Leandro Lantigua-Somoano, David Manley, Anthony Cardinale, Muhammad Zulfiqah Sadikan, Saurabh Kadyan, Donya Shahamati, Lorena Dias, Amber Wood, Cinthia Chavarria, Sara K. Rosenkranz, Neda S. Akhavan

Department of Medicine Faculty Publications

Cardiovascular-kidney-metabolic (CKM) syndrome integrates excess adiposity, metabolic dysfunction, kidney impairment, subclinical cardiovascular diseases, and clinical events along a staged continuum that invites unified prevention and treatment. Ultra-processed foods (UPFs) are a complex, high-prevalence exposure that may influence risk across CKM stages through nutrient profiles, additives, processing-induced compounds, and packaging-related contaminants. This review synthesizes epidemiologic, mechanistic, and translational evidence with attention to exposure definition and analytic rigor. We summarize NOVA-based UPF operationalization across dietary assessment tools, highlighting misclassification of mixed dishes, brand heterogeneity, and energy under-reporting, and we propose further examination of energy-adjusted models, calibration, and harmonized metrics. Observational studies consistently …

The Gut-Heart Axis: Exploring The Role Of The Gut Microbiome In Cardiovascular Health-A Focused Systematic Review, Yahya Makkieh, Haider Hussain Shah, Sakan Binte Imran, Shadman Mahmood Mahmood Khan Pathan, Anagha Chirayath Saju, Mounica Majooju, Aastha Garg, Tarun Naag, Rabeeul Islam, Cheeranthodika Fahima, Ramsha Ali

Electrical & Computer Engineering Faculty Publications

This focused systematic review examines the role of the gut microbiota in cardiovascular disease (CVD). The review explores mechanisms linking gut dysbiosis with CVD via microbial metabolites such as trimethylamine-Noxide (TMAO) and short-chain fatty acids (SCFAs), which affect inflammation, endothelial function, and lipid metabolism. Interventions including dietary modifications, probiotics, prebiotics, fecal microbiota transplantation, and pharmacological agents such as statins, rifaximin, and empagliflozin are evaluated for their impact on microbial composition and cardiovascular outcomes. Probiotic strains and fiber-rich diets demonstrated modest improvements in blood pressure, lipid profiles, and inflammatory markers. Studies revealed that gut microbiome alterations influence drug metabolism and bleeding …

Single-Cell Transcriptomic Analysis Of Peripheral Blood Mononuclear Cells Reveals Key Immune Responses In St-Segment Elevation Myocardial Infarction, Zheng Zhang, Shengfang Wang, Yahui Liu, Gaohan Li, Qianqian Cheng, Wei Yang, Gan-Xin Yan, Chuanyu Gao

Department of Medicine Faculty Papers

BACKGROUND: Inflammation plays a crucial role in the pathogenesis of ST-segment elevation myocardial infarction (STEMI). However, the precise immunological mechanisms remain incompletely understood. Single-cell RNA sequencing (scRNA-seq) provides a powerful approach to dissect immune cell heterogeneity and dynamic changes at single-cell resolution.

METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from 7 STEMI patients (within 6h after primary percutaneous coronary intervention) and 3 healthy controls. Single-cell suspensions were prepared and subjected to scRNA-seq using the 10x Genomics Chromium platform and Illumina NovaSeq 6000. Data were processed using Cell Ranger and analyzed with Seurat for quality control, clustering, and annotation. Differentially …

Targeting Kinin B1r Attenuates Hypertension Through At1r-Dependent Mechanisms, Drew Theobald, Riley N. Bessetti, Yumei Feng Earley, Eric Lazartigues, Karen Litwa, Srinivas Sriramula

School of Medicine Faculty Publications

BACKGROUND: Neurogenic hypertension is chronically high blood pressure that is initiated and maintained through excessive sympathetic nervous system activity and has been associated with increased B1R (kinin B1 receptor) activation. We previously reported a central role for B1R in mediating inflammatory pathways in the development of deoxycorticosterone acetate salt hypertension. Additionally, we identified a causal relationship between B1R expression after Ang II (angiotensin II) stimulation, and that B1R can mediate the bidirectional interaction between neuroinflammation and oxidative stress. However, whether there are any interactions between AT1R (Ang II-type I receptor) and B1R, and if B1R can mediate the effects of …

Impacts Of Radiation On Metabolism And Vascular Cell Senescence, Junichi Abe, Khanh Chau, Anahita Mojiri, Guangyu Wang, Masayoshi Oikawa, Venkata S K Samanthapudi, Abigail M Osborn, Keila C Ostos-Mendoza, Karla N Mariscal-Reyes, Tammay Mathur, Abhishek Jain, Joerg Herrmann, Syed Wamique Yusuf, Sunil Krishnan, Anita Deswal, Steven H Lin, Sivareddy Kotla, John P Cooke, Nhat-Tu Le

Faculty, Staff and Student Publications

Significance: This review investigates how radiation therapy (RT) increases the risk of delayed cardiovascular disease (CVD) in cancer survivors. Understanding the mechanisms underlying radiation-induced CVD is essential for developing targeted therapies to mitigate these effects and improve long-term outcomes for patients with cancer.

Recent Advances: Recent studies have primarily focused on metabolic alterations induced by irradiation in various cancer cell types. However, there remains a significant knowledge gap regarding the role of chronic metabolic alterations in normal cells, particularly vascular cells, in the progression of CVD after RT.

Critical Issues: This review centers on RT-induced metabolic alterations in vascular cells …

The Role Of Tgfβ-Activated Kinase 1 In Fibroblast Differentiation And Cardiac Remodeling After Injury., Daniel Chien Nguyen

Electronic Theses and Dissertations

Immediately following myocardial injury, a robust reparative response is orchestrated through intercellular communication. While various cell populations play critical roles in this process, cardiac fibroblasts have long been recognized as essential mediators of collagen synthesis and scar maturation; however, recent investigations have uncovered significant heterogeneity within the cardiac fibroblast population, revealing distinct subpopulations with roles that extend beyond their traditional functions. Notably, after tissue injury, fibroblasts exposed to damage signals can transition to an inflammatory phenotype, utilizing paracrine and autocrine signaling to coordinate immune cell recruitment and activation. Yet, the mechanisms underlying inflammatory cardiac fibroblast differentiation and their influence on …

Atherosclerosis: A Comprehensive Review Of Molecular Factors And Mechanisms, Vasiliki Tasouli-Drakou, Ian Ogurek, Taha Shaikh, Marc Ringor, Michael V. Dicaro, Kachon Lei

Department of Internal Medicine Faculty Research

Atherosclerosis, a condition characterized by the accumulation of lipids and a culprit behind cardiovascular events, has long been studied. However, in recent years, there has been an increase in interest in its initiation, with researchers shifting focus from traditional pathways involving the vascular infiltration of oxidized lipids and towards the novel presence of chronic inflammatory pathways. The accumulation of pro-inflammatory cytokines, in combination with the activation of transcription factors, creates a positive feedback loop that drives the creation and progression of atherosclerosis. From the upregulation of the nod-like receptor protein 3 (NLRP3) inflammasome and the Notch and Wnt pathways to …

The Effects Of Sglt2 Inhibitors In Patients With Metabolic Dysfunction-Associated Fatty Liver Disease; A Narrative Review, Mihaela Simona Popoviciu, Lorena Paduraru, Mominur Rahman, Fatema Akter Supti, Roxana Adriana Stoica, Delia Reurean Pintilei, Cristina Ioana Bica, Simona Cavalu

Journal of Mind and Medical Sciences

Worldwide, metabolic dysfunction-associated fatty liver disease (MAFLD) is a significant public health concern, especially since more than fifty percent of people with type 2 diabetes are affected by it. This pathological condition includes all states of fatty liver disease, from non-alcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH). Prolonged evolutions can lead to cirrhosis and cancer, so treatment must be started early. Hepatic steatosis may be improved by sodium glucose co-transporter 2 inhibitors (SGLT2 inhibitors), which prevent glucose reabsorption in the proximal renal tubule and increase urinary excretion, thus lowering plasma glucose levels. Experimental studies in animal models have suggested …

Chronic Glp1 Therapy Reduces Postprandial Il6 In Obese Humans With Prediabetes, Vala Hamidi, Hongyu Wang, Vi Pham, Karla Bermudez Saint Andre, Heinrich Taegtmeyer, Absalon D Gutierrez

Faculty, Staff and Student Publications

Single-dose glucagon-like peptide 1 (GLP1) therapy increases postprandial plasma IL6 levels in prediabetic, obese humans. GLP1-IL6 interactions underly multiple antidiabetic effects, but these may differ after acute versus chronic therapy. This study examines postprandial effects of GLP1 after chronic therapy. Seven humans (six Black) with prediabetes and obesity completed 6 weeks of exenatide extended release therapy. Then subjects returned for pre- and post-meal measurements of plasma IL6, GLP1, glucagon, and related inflammatory markers. Weight, which was measured before and after therapy, did not change. Plasma IL6 decreased from baseline to postmeal state ( = 0.016), with decreases in free fatty …

The Role Of Micrornas In Cellular Senescence, Inflammation, And Cancer Induced By Childhood Obesity, Sarah S. Siddiqi

Honors Undergraduate Theses

Childhood obesity has escalated into a major public health crisis with serious implications for long-term health. As obesity rates among children continue to rise globally, it is crucial to understand its effects on cellular aging and inflammation—key processes that underpin many metabolic diseases. Obesity not only directly contributes to various metabolic disorders but also disrupts fundamental cellular mechanisms, accelerating aging and fostering systemic inflammation. By examining the impact of obesity on cellular aging and chronic inflammation, as well as the regulatory role of microRNAs (miRNAs) in these pathways, we have been able to identify critical biomarkers and molecular mechanisms involved …

Eicosanoid And Eicosanoid-Related Inflammatory Mediators And Exercise Intolerance In Heart Failure With Preserved Ejection Fraction, Emily S Lau, Athar Roshandelpoor, Shahrooz Zarbafian, Dongyu Wang, James S Guseh, Norrina Allen, Vinithra Varadarajan, Matthew Nayor, Ravi V Shah, Joao A C Lima, Sanjiv J Shah, Bing Yu, Mona Alotaibi, Susan Cheng, Mohit Jain, Gregory D Lewis, Jennifer E Ho

Faculty, Staff and Student Publications

Systemic inflammation has been implicated in the pathobiology of heart failure with preserved ejection fraction (HFpEF). Here, we examine the association of upstream mediators of inflammation as ascertained by fatty-acid derived eicosanoid and eicosanoid-related metabolites with HFpEF status and exercise manifestations of HFpEF. Among 510 participants with chronic dyspnea and preserved LVEF who underwent invasive cardiopulmonary exercise testing, we find that 70 of 890 eicosanoid and related metabolites are associated with HFpEF status, including 17 named and 53 putative eicosanoids (FDR q-value < 0.1). Prostaglandin (15R-PGF2α, 11ß-dhk-PGF2α) and linoleic acid derivatives (12,13 EpOME) are associated with greater odds of HFpEF, while epoxides (8(9)-EpETE), docosanoids (13,14-DiHDPA), and oxylipins (12-OPDA) are associated with lower odds of HFpEF. Among 70 metabolites, 18 are associated with future development of heart failure in the community. Pro- and anti-inflammatory eicosanoid and related metabolites may contribute to the pathogenesis of HFpEF and serve as potential targets for intervention.

Usp38 Exacerbates Atrial Inflammation, Fibrosis, And Susceptibility To Atrial Fibrillation After Myocardial Infarction In Mice, Yang Gong, Tingting Yu, Wei Shuai, Tao Chen, Jingjing Zhang, He Huang

Faculty, Staff and Student Publications

BACKGROUND: Inflammation plays an important role in the pathogenesis of atrial fibrillation (AF) after myocardial infarction (MI). The role of USP38, a member of the ubiquitin-specific protease family, on MI-induced atrial inflammation, fibrosis, and associated AF is unclear.

METHODS: In this study, we surgically constructed a mouse MI model using USP38 cardiac conditional knockout (USP38-CKO) and cardiac-specific overexpression (USP38-TG) mice and applied biochemical, histological, electrophysiological characterization and molecular biology to investigate the effects of USP38 on atrial inflammation, fibrosis, and AF and its mechanisms.

RESULTS: Our results revealed that USP38-CKO attenuates atrial inflammation, thereby ameliorating fibrosis, and abnormal electrophysiologic properties, …

Association Of Interleukin-6 And Interleukin-18 With Cardiovascular Disease In Older Adults: Atherosclerosis Risk In Communities Study, Xiaoming Jia, Leo Buckley, Caroline Sun, Mahmoud Al Rifai, Bing Yu, Vijay Nambi, Salim S Virani, Elizabeth Selvin, Kunihiro Matsushita, Ron C Hoogeveen, Josef Coresh, Amil M Shah, Christie M Ballantyne

Faculty, Staff and Students Publications

AIMS: Interleukin-6 (IL-6) and interleukin-18 (IL-18), important cytokines implicated in atherosclerosis and inflammaging, were assessed for associations with global cardiovascular disease (CVD), atrial fibrillation (AF), and death in older adults.

METHODS AND RESULTS: Participants from Atherosclerosis Risk in Communities study Visit 5 (mean age 75.4 ± 5.1 years) with IL-6 and IL-18 measurements were included (n = 5672). Cox regression models were used to assess associations of IL-6 and IL-18 with coronary heart disease (CHD), ischaemic stroke, heart failure (HF) hospitalization, global CVD (composite of CHD, stroke, and HF), AF, and all-cause death. Over a median follow-up of 7.2 years, …

Untargeted Metabolomic Analysis Investigating Links Between Unprocessed Red Meat Intake And Markers Of Inflammation, Alexis C Wood, Goncalo Graca, Meghana Gadgil, Mackenzie K Senn, Matthew A Allison, Ioanna Tzoulaki, Philip Greenland, Timothy Ebbels, Paul Elliott, Mark O Goodarzi, Russell Tracy, Jerome I Rotter, David Herrington

Faculty, Staff and Students Publications

BACKGROUND: Whether red meat consumption is associated with higher inflammation or confounded by increased adiposity remains unclear. Plasma metabolites capture the effects of diet after food is processed, digested, and absorbed, and correlate with markers of inflammation, so they can help clarify diet-health relationships.

OBJECTIVE: To identify whether any metabolites associated with red meat intake are also associated with inflammation.

METHODS: A cross-sectional analysis of observational data from older adults (52.84% women, mean age 63 ± 0.3 y) participating in the Multi-Ethnic Study of Atherosclerosis (MESA). Dietary intake was assessed by food-frequency questionnaire, alongside C-reactive protein (CRP), interleukin-2, interleukin-6, fibrinogen, …

Circulating Neutrophil-Related Proteins Associate With Incident Heart Failure And Cardiac Dysfunction: The Aric Study, Leo F Buckley, Pranav Dorbala, Brian L Claggett, Peter Libby, Weihong Tang, Josef Coresh, Christie M Ballantyne, Ron C Hoogeveen, Bing Yu, Amil M Shah

Faculty, Staff and Student Publications

AIMS: Neutrophil activity contributes to adverse cardiac remodelling in experimental acute cardiac injury and is modifiable with pharmacologic agents like colchicine.

METHODS AND RESULTS: Neutrophil activity-related plasma proteins known to be affected by colchicine treatment were measured at Visit 3 (1993-1995) and Visit 5 (2011-2013) of the ARIC cohort study. A protein-based neutrophil activity score was derived from 10 candidate proteins using LASSO Cox regression. Associations with incident heart failure (HF) and with cardiac function using Cox proportional hazards regression and linear regression models, respectively. The mean ages at Visits 3 and 5 were 60 ± 6 and 75 ± …

Impact Of Geroscience On Therapeutic Strategies For Older Adults With Cardiovascular Disease: Jacc Scientific Statement, Daniel E Forman, George A Kuchel, John C Newman, James L Kirkland, Elena Volpi, George E Taffet, Nir Barzilai, Ambarish Pandey, Dalane W Kitzman, Peter Libby, Luigi Ferrucci

Faculty, Staff and Students Publications

Geroscience posits that cardiovascular disease (CVD) and other chronic diseases result from progressive erosion of the effectiveness of homeostatic mechanisms that oppose age-related accumulation of molecular damage. This hypothetical common root to chronic diseases explains why patients with CVD are often affected by multimorbidity and frailty and why older age negatively affects CVD prognosis and treatment response. Gerotherapeutics enhance resilience mechanisms that counter age-related molecular damage to prevent chronic diseases, frailty, and disability, thereby extending healthspan. Here, we describe the main resilience mechanisms of mammalian aging, with a focus on how they can affect CVD pathophysiology. We next present novel …

Mavs Signaling Is Required For Preventing Persistent Chikungunya Heart Infection And Chronic Vascular Tissue Inflammation, Maria G Noval, Sophie N Spector, Eric Bartnicki, Franco Izzo, Navneet Narula, Stephen T Yeung, Payal Damani-Yokota, M Zahidunnabi Dewan, Valeria Mezzano, Bruno A Rodriguez-Rodriguez, Cynthia Loomis, Kamal M Khanna, Kenneth A Stapleford

Faculty, Staff and Student Publications

Chikungunya virus (CHIKV) infection has been associated with severe cardiac manifestations, yet, how CHIKV infection leads to heart disease remains unknown. Here, we leveraged both mouse models and human primary cardiac cells to define the mechanisms of CHIKV heart infection. Using an immunocompetent mouse model of CHIKV infection as well as human primary cardiac cells, we demonstrate that CHIKV directly infects and actively replicates in cardiac fibroblasts. In immunocompetent mice, CHIKV is cleared from cardiac tissue without significant damage through the induction of a local type I interferon response from both infected and non-infected cardiac cells. Using mice deficient in …

Crat Links Cholesterol Metabolism To Innate Immune Responses In The Heart, Hua Mao, Aude Angelini, Shengyu Li, Guangyu Wang, Luge Li, Cam Patterson, Xinchun Pi, Liang Xie

Faculty, Staff and Students Publications

Chronic inflammation is associated with increased risk and poor prognosis of heart failure; however, the precise mechanism that provokes sustained inflammation in the failing heart remains elusive. Here we report that depletion of carnitine acetyltransferase (CRAT) promotes cholesterol catabolism through bile acid synthesis pathway in cardiomyocytes. Intracellular accumulation of bile acid or intermediate, 7α-hydroxyl-3-oxo-4-cholestenoic acid, induces mitochondrial DNA stress and triggers cGAS-STING-dependent type I interferon responses. Furthermore, type I interferon responses elicited by CRAT deficiency substantially increase AIM2 expression and AIM2-dependent inflammasome activation. Genetic deletion of cardiomyocyte CRAT in mice of both sexes results in myocardial inflammation and dilated cardiomyopathy, …

Targeting Neddylation And Sumoylation In Chemoresistant Triple Negative Breast Cancer, Wei Ruan, Jiwen Li, Seungwon Choi, Xinxin Ma, Yafen Liang, Ragini Nair, Xiaoyi Yuan, Tingting W Mills, Holger K Eltzschig

Faculty, Staff and Student Publications

Previous studies implicate extracellular adenosine signaling in attenuating myocardial ischemia and reperfusion injury (IRI). This extracellular adenosine signaling is terminated by its uptake into cells by equilibrative nucleoside transporters (ENTs). Thus, we hypothesized that targeting ENTs would function to increase cardiac adenosine signaling and concomitant cardioprotection against IRI. Mice were exposed to myocardial ischemia and reperfusion injury. Myocardial injury was attenuated in mice treated with the nonspecific ENT inhibitor dipyridamole. A comparison of mice with global Ent1 or Ent2 deletion showed cardioprotection only in Ent1-/- mice. Moreover, studies with tissue-specific Ent deletion revealed that mice with myocyte-specific Ent1 deletion (Ent1loxP/loxP …

Combination Sodium Nitrite And Hydralazine Therapy Attenuates Heart Failure With Preserved Ejection Fraction Severity In A “2-Hit” Murine Model, Kyle B. Lapenna, Zhen Li, Jake E. Doiron, Thomas E. Sharp, Huijing Xia, Karl Moles, Kashyap Koul, John S. Wang, David J. Polhemus, Traci T. Goodchild, Ravi B. Patel, Sanjiv J. Shah, David J. Lefer

School of Medicine Faculty Publications

BACKGROUND: Recent studies have suggested that cardiac nitrosative stress mediated by pathological overproduction of nitric oxide (NO) via inducible NO synthase (iNOS) contributes to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Other studies have suggested that endothelial NO synthase (eNOS) dysfunction and attenuated NO bioavailability contribute to HFpEF morbidity and mortality. We sought to further investigate dysregulated NO signaling and to examine the effects of a NO-based dual therapy (sodium nitrite+hydralazine) following the onset of HFpEF using a “2-hit” murine model. METHODS AND RESULTS: Nine-week-old male C57BL/6 N mice (n=15 per group) were treated concurrently with high-fat …

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

Faculty, Staff and Student Publications

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

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

The Impact Of Whole Fruits High In Anthocyanins On Blood Lipids In Middle-Aged Women, Denise N. Leininger

Cal Poly Humboldt theses and projects

Cardiometabolic Diseases (CMDs) are the leading cause of morbidity and mortality among women. During the menopause transition, drops in estrogen play a favorable role in the excess accumulation of Intraabdominal Fat (IAF), altering blood lipid metabolism and inducing inflammatory responses in CMDs attributed to dyslipidemia. This systematic review and meta-analysis examined current research on the effects of whole fruits high in anthocyanins on blood lipid metabolism in women at risk for CMDs. This meta-analysis included 15 studies using the PRISMA 2020 guidelines. Overall, effect sizes were not significant when exploring blood lipid marker outcomes High-Density Lipoprotein (HDL), Low-Density Lipoprotein (LDL), …

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

Faculty, Staff and Student Publications

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

Perinatal Exercise Effectiveness To Prevent Offspring High-Altitude Pulmonary Hypertension, Eric Leslie

Health, Exercise, and Sports Sciences ETDs

The effectiveness of perinatal exercise (i.e., exercise by mothers immediately prior to, throughout, and after pregnancy) to attenuate high-altitude pulmonary hypertension and associated health consequences in the offspring exposed to chronic hypoxia in early life was investigated. Four groups were used to compare the effects of perinatal exercise to offspring exposed to low altitude (i.e., normoxic) conditions or simulated 4500 meters of high altitude (i.e., hypoxic) as well as their respective, sedentary controls. Offspring in the hypoxic groups had lower body weights and tail lengths as well as higher hematocrits, right ventricular systolic pressures, and right heart weights. The hypoxic …

Association Of Apremilast With Vascular Inflammation And Cardiometabolic Function In Patients With Psoriasis: The Vip-A Phase 4, Open-Label, Nonrandomized Clinical Trial, Joel M Gelfand, Daniel B Shin, April W Armstrong, Stephen K Tyring, Andrew Blauvelt, Scott Gottlieb, Benjamin N Lockshin, Robert E Kalb, Robert Fitzsimmons, Justin Rodante, Philip Parel, Grigory A Manyak, Laurel Mendelsohn, Megan H Noe, Maryte Papadopoulos, Maha N Syed, Thomas J Werner, Joy Wan, Martin P Playford, Abass Alavi, Nehal N Mehta

Faculty, Staff and Student Publications

IMPORTANCE: Psoriasis is an inflammatory condition associated with metabolic and cardiovascular disease. Apremilast, a phosphodiesterase 4 inhibitor, is commonly used for psoriasis and can cause weight loss.

OBJECTIVE: To determine the association between apremilast and aortic vascular inflammation as assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), cardiometabolic markers (primary outcomes at week 16), and abdominal fat composition.

DESIGN, SETTING, AND PARTICIPANTS: A single-arm, open-label, interventional, nonrandomized clinical trial in which the imaging and laboratory outcomes were measured by an investigator who was blinded to time was conducted between April 11, 2017, and August 17, 2021, at 7 dermatology sites …

Inflammatory Links Between Hypertriglyceridemia And Atherogenesis, Xueying Peng, Huaizhu Wu

Faculty, Staff and Students Publications

Purpose of Review

Recent studies indicate an association between hypertriglyceridemia (HTG) and atherosclerotic cardiovascular disease (ASCVD). The purpose of this review is to discuss the potential mechanism connecting HTG and ASCVD risk and the potential efficacy of HTG-targeting therapies in ASCVD prevention.

Recent Findings

HTG, with elevations in triglyceride-rich lipoproteins (TGRL) and their remnants, are causal ASCVD risk factors. The mechanisms whereby HTG increases ASCVD risk are not well understood but may include multiple factors. Inflammation plays a crucial role in atherosclerosis. TGRL compared to low-density lipoproteins (LDL) correlate better with inflammation. TGRL remnants can penetrate endothelium and interact with …

Inflammatory Bowel Disease And Atherosclerotic Cardiovascular Disease In U.S. Adults-A Population-Level Analysis In The National Health Interview Survey, Khurram Nasir, Isaac Acquah, Amit K. Dey, Tanushree Agrawal, Syed Zawahir Hassan, Kerri Glassner, Bincy Abraham, Eamonn M M. Quigley, Ron Blankstein, Salim S. Virani

Office of the Provost

Objectives: To evaluate the association between inflammatory bowel disease (IBD) and atherosclerotic cardiovascular disease (ASCVD) and whether this association is modified by age or sex.
Methods: We conducted a cross-sectional analysis using data from the 2015-2016 National Health Interview Survey (NHIS). The exposure of interest was self-reported IBD. The outcome of interest was prevalent ASCVD, which included a history of angina, myocardial infarction or stroke. We used survey-specific descriptive statistics to obtain weighted national estimates for IBD and ASCVD prevalence. Logistic regression models were used to assess the association between IBD and ASCVD, progressively adjusting for demographics and traditional risk …

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 …

Arrhythmogenic Hearts In Pkd2 Mutant Mice Are Characterized By Cardiac Fibrosis, Systolic, And Diastolic Dysfunctions, Farideh Amirrad, Rajasekharreddy Pala, Kiumars Shamloo, Brian S. Muntean, Surya M. Nauli

Pharmacy Faculty Articles and Research

Autosomal dominant polycystic kidney disease (PKD) is a hereditary disorder affecting multiple organs, including the heart. PKD has been associated with many cardiac abnormalities including the arrhythmogenic remodeling in clinical evaluations. In our current study, we hypothesized that Pkd2 gene mutation results in structural and functional defects in the myocardium. The structural and functional changes of Pkd2 mutant hearts were analyzed in the myocardial-specific Pkd2 knockout (KO) mouse. We further assessed a potential role of TGF-b₁ signaling in the pathology of Pkd2-KO hearts. Hearts from age-matched 6-month-old MyH6•Pkd2^wt/wt (control or wild-type) and MyH6 …