Medicine and Health Sciences Commons^™

Mechanisms Of Cigarette Smoke-Induced Mitochondrial Dysfunction In Striated Muscle And Aorta, Stephen T. Decker

Doctoral Dissertations

Cigarette Smoke is a significant cause of morbidity and mortality in the United States, accounting for over 480,000 annual deaths. Of these deaths, the most common cause of mortality in chronic smokers is cardiometabolic diseases. Likewise, a significant portion of smokers experience some form of cardiac, vascular, or metabolic dysfunction throughout their lifetime. More specifically, smoking is shown to induce mitochondrial dysfunction in these tissues, causing an increase in oxidative damage and poor overall health. However, despite the advances in the health outcomes related to cigarette smoke exposure, the mechanisms underlying mitochondrial dysfunction in striated muscle and the vasculature remain …

Mechanism Of Rare Variant In Acta2, P.Arg149cys, Driving Diverse Vascular Disease, Kaveeta Kaw

Dissertations & Theses (Open Access)

Heterozygous variants in ACTA2 (smooth muscle (SM) α-actin) predispose to thoracic aortic aneurysms and dissections (TAAD) and early-onset coronary artery disease (CAD). The most common ACTA2 mutation is a genetic alteration of arginine 149 to a cysteine, ACTA2 p.Arg149Cys, which accounts for disease in 24% of all ACTA2 mutation carriers.(1) ACTA2 p.Arg149Cys mutation carriers present with either TAAD or CAD but rarely have both diseases. To identify the molecular mechanisms dictating whether an individual with ACTA2 p.Arg149Cys develops TAAD or CAD, CRISPR/Cas9 technology was used to generate the mutant mouse, Acta2^R149C/+, in a C57BL6 background. Acta2^R149C/+ mice …

Aortic Aneurysms, Trevor Cowles

Nursing Student Class Projects (Formerly MSN)

An aortic aneurysm is an abnormal bulge that occurs in the wall of the major blood vessel (aorta) that carries blood from your heart to your body. Aortic aneurysms can occur anywhere in your aorta and may be tube-shaped (fusiform) or round (saccular). This poster is about the pathophysiology of how these abnormal bulges occur. It also covers the significance of the pathophysiology along with the clinical picture of what to expect if an individual experiences these mechanisms behind the pathophysiology.

Nicotinamide Riboside And The Aortic Response To Angiotensin Ii Infusion In Mice, Sina A. Ghoreishi

Electronic Thesis and Dissertation Repository

Damage to vascular cells of the aorta drives vascular dysfunction and disease. Nicotinamide adenine dinucleotide (NAD⁺) is a cellular metabolite critical to cellular health, but NAD⁺ levels decline during oxidative insults and aging. The NAD⁺ precursor, nicotinamide riboside (NR) can augment NAD⁺ levels. Herein, I determined whether orally administrated NR could protect the aorta of middle-aged mice from acute and sustained angiotensin II (Ang II) infusion-induced damage. I demonstrate that orally administered NR can protect the aorta from damage imposed by Ang II.

Genetic Predisposition And M1 Macrophage Polarization Created By Elastin-Derived Peptides Drive Abdominal Aortic Aneurysm Formation, Matthew A. Dale

Theses & Dissertations

Abdominal aortic aneurysm (AAA) is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix (ECM) degradation. Evidence has demonstrated a profound influence of genetic background on AAA formation. The work presented herein discusses two studies: the first demonstrates how genetic components can enhance the susceptibility to AAA formation and the second demonstrates how ECM degradation enhances AAA progression by influencing inflammatory cell phenotypes. An understanding of the pathways involved in AAA pathogenesis can help not only to identify potential patients at risk of AAA development, a heritable disease in which the incriminating component has yet to be …

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 …

Characterization Of The Vascular Pathology In The Acta2 R258c Mouse Model And Cerebrovascular Characterization Of The Acta2 Null Mouse, Carlos A. Villamizar

Dissertations & Theses (Open Access)

Mutations in ACTA2, the gene encoding for smooth muscle α-actin, predispose patients to a wide range of vascular diseases and is most commonly associated with thoracic aortic aneurysms (TAAD) and dissections (TAAD) and strokes. TAAD in patients is characterized by aortic media degeneration and loss in contractile force generation followed by aortic enlargement and subsequent rupture. Most stroke cases associated with ACTA2 are described as moyamoya-like cerebrovascular incidents characterized by distal occlusion of the internal carotid artery, stenosis of arteries in the Circle of Willis, and straightening of cerebral arteries. Patient samples are scarcely available for analysis, and the few …

Numerical Modeling Of Hemodynamics In The Thoracic Aorta And Alterations By Dacron Patch Treatment Of Aortic Coarctation, Ronak Jashwant Dholakia

Master's Theses (2009 -)

Coarctation of the aorta (CoA) is a major congenital heart disease, characterized by a severe stenosis of the proximal descending thoracic aorta. Traditionally, surgery has been the treatment of choice for CoA. Dacron patch aortoplasty gained increased popularity after its introduction in the mid-twentieth century due to its advantages over other surgical treatment methods available at the time. A major complication with Dacron patch aortoplasty has been the formation of late aneurysm with as much as 51% incidence reported in follow up studies. The change in aortic morphology and formation of aneurysms after Dacron patch surgery could lead to local …

Effects Of Aging On Pressure-Induced Mapk Activation In The Rat Aorta, Kevin M. Rice

Theses, Dissertations and Capstones

With age, the cardiovascular system experiences substantial alterations in cellular morphology and function. The factors regulating these changes are unknown; however, the mitogen activated protein kinase (MAPK) pathways have emerged as critical components for mediating numerous cellular responses including control of cell growth, differentiation and adaptation. Here we compare the expression, basal activation and the ability of increased pressure to activate the MAPK pathways in adult (6 month old), aged (30 month old) and very aged (36 month old) Fischer 344 x Brown Norway F1 Hybrid rats. Histochemical analysis demonstrated an age-related increase in tunica media thickness of approximately 11% …

Evidence For Absence Of Latchbridge Formation In Phasic Saphenous Artery, Shaojie Han

Theses and Dissertations

Tonic arterial smooth muscle can produce strong contractions indefinitely by formation of slowly cycling crossbridges (latchbridges) that maintain force at a high energy economy. To fully understand the uniqueness of mechanisms regulating tonic arterial contraction, comparisons have been made to phasic visceral smooth muscles that do not sustain high forces. This study explored mechanisms of force maintenance in a phasic artery by comparing KCl-induced contractions in the tonic, femoral artery (FA) and its primary branch, the phasic saphenous artery (SA). KCl rapidly (5 N/m2) and [ca2+]i (250 nM) in FA and SA. By 10 min, [ca2+]i declined to 175 nM …