Physiology Commons^™

Characterization Of Spontaneous Preeclampsia In The African Green Monkey (Chlorocebus Aethiops Sabaeus), Chelsea Christina Weaver

Theses and Dissertations--Biology

Hypertensive pregnancy disorders are a major contribution to maternal and neonatal mortality worldwide. Two of these disorders, preeclampsia and chronic hypertension in pregnancy, affect up to 10% of all pregnancies. These hypertensive disorders of pregnancy are associated with long-term, postnatal risk factors for both mother and offspring. Despite numerous recent advances in preeclampsia research, the underlying mechanisms are still not understood. This could be due to lack of a spontaneous animal model. This dissertation presents the African Green Monkey (AGM; Chlorocebus aethiops sabaeus) as the first known spontaneous animal model of preeclampsia and a highly translational model of chronic …

Dennd5b Regulates Intestinal Triglyceride Absorption And Body Mass, Scott M. Gordon, Edward B. Neufeld, Zhihong Yang, Milton Pryor, Lita A. Freeman, Xiao Fan, Iftikhar J. Kullo, Leslie G. Biesecker, Alan T. Remaley

Saha Cardiovascular Research Center Faculty Publications

Regulation of lipid absorption by enterocytes can influence metabolic status in humans and contribute to obesity and related complications. The intracellular steps of chylomicron biogenesis and transport from the Endoplasmic Reticulum (ER) to the Golgi complex have been described, but the mechanisms for post-Golgi transport and secretion of chylomicrons have not been identified. Using a newly generated Dennd5b^−/− mouse, we demonstrate an essential role for this gene in Golgi to plasma membrane transport of chylomicron secretory vesicles. In mice, loss of Dennd5b results in resistance to western diet induced obesity, changes in plasma lipids, and reduced aortic atherosclerosis. In …

Hyperhomocysteinemia As A Risk Factor For Vascular Contributions To Cognitive Impairment And Dementia, Brittani R. Price, Donna M. Wilcock, Erica M. Weekman

Physiology Faculty Publications

Behind only Alzheimer’s disease, vascular contributions to cognitive impairment and dementia (VCID) is the second most common cause of dementia, affecting roughly 10–40% of dementia patients. While there is no cure for VCID, several risk factors for VCID, such as diabetes, hypertension, and stroke, have been identified. Elevated plasma levels of homocysteine, termed hyperhomocysteinemia (HHcy), are a major, yet underrecognized, risk factor for VCID. B vitamin deficiency, which is the most common cause of HHcy, is common in the elderly. With B vitamin supplementation being a relatively safe and inexpensive therapeutic, the treatment of HHcy-induced VCID would seem straightforward; however, …

Editorial: Ion Channel Trafficking And Cardiac Arrhythmias, Marcel A. G. Van Der Heyden, Brian P. Delisle, Hugues Abriel

Physiology Faculty Publications

No abstract provided.

Apoe And Alzheimer’S Disease: Neuroimaging Of Metabolic And Cerebrovascular Dysfunction, Jason A. Brandon, Brandon C. Farmer, Holden C. Williams, Lance A. Johnson

Physiology Faculty Publications

Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for late onset Alzheimer’s Disease (AD), and is associated with impairments in cerebral metabolism and cerebrovascular function. A substantial body of literature now points to E4 as a driver of multiple impairments seen in AD, including blunted brain insulin signaling, mismanagement of brain cholesterol and fatty acids, reductions in blood brain barrier (BBB) integrity, and decreased cerebral glucose uptake. Various neuroimaging techniques, in particular positron emission topography (PET) and magnetic resonance imaging (MRI), have been instrumental in characterizing these metabolic and vascular deficits associated with this important AD risk factor. In …

Adropin: An Endocrine Link Between The Biological Clock And Cholesterol Homeostasis, Sarbani Ghoshal, Joseph R. Stevens, Cyrielle Billon, Clemence Girardet, Sadichha Sitaula, Arthur S. Leon, D.C. Rao, James S. Skinner, Tuomo Rankinen, Claude Bouchard, Marinelle V. Nuñez, Kimber L. Stanhope, Deborah A. Howatt, Alan Daugherty, Jinsong Zhang, Matthew Schuelke, Edward P. Weiss, Alisha R. Coffey, Brian J. Bennett, Praveen Sethupathy, Thomas P. Burris, Peter J. Havel, Andrew A. Butler

Physiology Faculty Publications

Objective

Identify determinants of plasma adropin concentrations, a secreted peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to metabolic control and vascular function.

Methods

Associations between plasma adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers of lipid and glucose metabolism were assessed in plasma obtained after an overnight fast in humans. The regulation of adropin expression was then assessed in silico, in cultured human cells, and in animal models.

Results

In humans, plasma adropin concentrations are inversely related to atherogenic LDL-cholesterol (LDL-C) levels in men (n = 349), but not in women (n = …

Mechanisms And Potential Therapy On Disrupted Blood Pressure Circadian Rhythm In Diabetes, Tianfei Hou

Theses and Dissertations--Pharmacology and Nutritional Sciences

Arterial blood pressure (BP) undergoes a 24-hour oscillation that peaks in the active day and reaches a nadir at night during sleep in humans. Reduced nocturnal BP fall (also known as non-dipper) is the most common disruption of BP circadian rhythm and is associated with increased risk of untoward cardiovascular events and target organ injury. Up to 75% of diabetic patients are non-dippers. However, the mechanisms underlying diabetes associated non-dipping BP are largely unknown. To address this important question, we generated a novel diabetic db/db-mPer2^Luc mouse model (db/db-mPer2^Luc) that allows quantitatively measuring of mPER2 protein oscillation …

Abnormal Contractility In Human Heart Myofibrils From Patients With Dilated Cardiomyopathy Due To Mutations In Ttn And Contractile Protein Genes, Petr G. Vikhorev, Natalia Smoktunowicz, Alex B. Munster, O'Neal Copeland, Sawa Kostin, Cecile Montgiraud, Andrew E. Messer, Mohammad R. Toliat, Amy Li, Cristobal G. Dos Remedios, Sean Lal, Cheavar A. Blair, Kenneth S. Campbell, Maya E. Guglin, Ralph Knoll, Steven B. Marston

Physiology Faculty Publications

Dilated cardiomyopathy (DCM) is an important cause of heart failure. Single gene mutations in at least 50 genes have been proposed to account for 25–50% of DCM cases and up to 25% of inherited DCM has been attributed to truncating mutations in the sarcomeric structural protein titin (TTNtv). Whilst the primary molecular mechanism of some DCM-associated mutations in the contractile apparatus has been studied in vitro and in transgenic mice, the contractile defect in human heart muscle has not been studied. In this study we isolated cardiac myofibrils from 3 TTNtv mutants, and 3 with contractile protein mutations (TNNI3 …

Transforming Growth Factor-Β In Thoracic Aortic Aneurysms: Good, Bad, Or Irrelevant?, Alan Daugherty, Zheying Chen, Hisashi Sawada, Debra L. Rateri, Mary B. Sheppard

Physiology Faculty Publications

No abstract provided.

Modulating Beta-Cardiac Myosin Function At The Molecular And Tissue Levels, Wanjian Tang, Cheavar A. Blair, Shane D. Walton, András Málnási-Csizmadia, Kenneth S. Campbell, Christopher M. Yengo

Physiology Faculty Publications

Inherited cardiomyopathies are a common form of heart disease that are caused by mutations in sarcomeric proteins with beta cardiac myosin (MYH7) being one of the most frequently affected genes. Since the discovery of the first cardiomyopathy associated mutation in beta-cardiac myosin, a major goal has been to correlate the in vitro myosin motor properties with the contractile performance of cardiac muscle. There has been substantial progress in developing assays to measure the force and velocity properties of purified cardiac muscle myosin but it is still challenging to correlate results from molecular and tissue-level experiments. Mutations that cause …

Myofilament Calcium Sensitivity: Consequences Of The Effective Concentration Of Troponin I, Jalal K. Siddiqui, Svetlana B. Tikunova, Shane D. Walton, Bin Liu, Meredith Meyer, Pieter P. De Tombe, Nathan Neilson, Peter M. Kekenes-Huskey, Hussam E. Salhi, Paul M.L. Janssen, Brandon J. Biesiadecki, Jonathan P. Davis

Chemistry Faculty Publications

Control of calcium binding to and dissociation from cardiac troponin C (TnC) is essential to healthy cardiac muscle contraction/relaxation. There are numerous aberrant post-translational modifications and mutations within a plethora of contractile, and even non-contractile, proteins that appear to imbalance this delicate relationship. The direction and extent of the resulting change in calcium sensitivity is thought to drive the heart toward one type of disease or another. There are a number of molecular mechanisms that may be responsible for the altered calcium binding properties of TnC, potentially the most significant being the ability of the regulatory domain of TnC to …

Cardiac Remodeling And Dysfunction In Childhood Obesity: A Cardiovascular Magnetic Resonance Study, Linyuan Jing, Cassi M. Binkley, Jonathan D. Suever, Nivedita Umasankar, Christopher M. Haggerty, Jennifer Rich, Christopher D. Nevius, Gregory J. Wehner, Sean M. Hamlet, David K. Powell, Aurelia Radulescu, H. Lester Kirchner, Frederick H. Epstein, Brandon K. Fornwalt

Pediatrics Faculty Publications

Background: Obesity affects nearly one in five children and is associated with increased risk of premature death. Obesity-related heart disease contributes to premature death. We aimed to use cardiovascular magnetic resonance (CMR) to comprehensively characterize the changes in cardiac geometry and function in obese children.

Methods and results: Forty-one obese/overweight (age 12 ± 3 years, 56 % female) and 29 healthy weight children (age 14 ± 3 years, 41 % female) underwent CMR, including both standard cine imaging and displacement encoded imaging, for a complete assessment of left ventricular (LV) structure and function. After adjusting for age, LV mass index …

Ppap2b Expression Limits Lesion Formation In Murine Models Of Atherosclerosis, Paul A. Mueller

Theses and Dissertations--Physiology

Coronary artery disease (CAD) is the leading cause of death in both men and women worldwide and is defined as a narrowing of the coronary arteries due to accumulation of atherosclerotic plaques. Genome-wide association studies have identified risk loci within the gene PPAP2B that confers increased risk of developing CAD. Evidence suggests these aforementioned SNPs are regulating PPAP2B expression in a cis-manner through the interruption of transcription factor binding sites. PPAP2B encodes the lipid phosphate phosphatase 3 enzyme that plays a key role in degrading bioactive lysophosphatidic acid (LPA). LPA has a plethora of effects on vascular tissue and is …

Development And Application Of Gadolinium Free Cardiac Magnetic Resonance Fibrosis Imaging For Multiscale Study Of Heart Failure In Patients With End Stage Renal Disease, Tori A. Stromp

Theses and Dissertations--Physiology

Cardiac magnetic resonance (CMR) is a powerful tool to noninvasively image ventricular fibrosis. Late gadolinium enhancement (LGE) CMR identifies focal and, with T1 mapping, diffuse fibrosis. Despite prevalent cardiac fibrosis and heart failure, patients with end stage renal disease (ESRD) are excluded from LGE. Absence of a suitable diagnostic has limited the understanding of heart failure and obstructed development of therapies in the setting of ESRD. A quantitative, gadolinium free fibrosis detection method could overcome this critical barrier, propelling the advancement of diagnostic, monitoring, and therapy options. This project describes the development of a gadolinium free CMR technique and application …

Lifestyle Contributors To Cardiovascular Disease Risk, Adam J. Berrones

Theses and Dissertations--Kinesiology and Health Promotion

Aortic stiffness is an independent risk factor that has prognostic value regarding future cardiovascular disease (CVD) events such as myocardial infarction, strokes, and heart failure. Although death rates due to coronary heart disease have declined in recent years, the leading global killer remains CVD and prevalence is still high. Understanding lifestyle contributors associated with aortic stiffness would provide the public with insight into targeting key health-related behaviors.

The purpose of this observational study was to examine the association of physical activity, physical function, and dietary quality as independent factors contributing to aortic stiffness in apparently healthy middle aged men. Fifty-two …