Cardiovascular Diseases Commons^™

Regulation Of C-Reactive Protein Gene Expression And Function, Avinash N. Thirumalai

Electronic Theses and Dissertations

Human C-reactive protein (CRP) is the prototypic acute phase protein whose serum concentration increases rapidly during inflammation. CRP is also associated with atherosclerosis; it is deposited at lesion sites where it may interact with modified lipoproteins. There are 2 major questions regarding CRP: 1. How is the serum concentration of CRP regulated? 2. What are the functions of CRP in atherosclerosis?

Our first aim was to determine the role of the constitutively expressed transcription factor Oct-1 in regulating CRP gene expression. We found that Oct-1 overexpression inhibited (IL-6+IL-1β)- induced CRP gene expression; maximal inhibition required the binding of Oct-1 to …

Effects Of An Angiotensin Ii Type 1 Receptor Blocker On Cardiovascular Calcification, Zachary B. Armstrong

Electronic Thesis and Dissertation Repository

Aims: Three types of cardiovascular calcification are commonly found in humans: arterial calcification, intimal calcification, and calcific aortic valve disease. Very little is known about the mechanisms driving cardiovascular calcification despite serious clinical implications and a clear association with morbidity and mortality. Indeed, it is even unclear whether the same factors are involved in arterial, intimal, and valvular calcification. The objective of this study was to elucidate the effects of an angiotensin II type 1 receptor blocker (ARB) on the progression of cardiovascular calcification in male New Zealand White rabbits. Where appropriate, statins were examined in conjunction and in combination …

The Role Of Angiotensinogen In Atherosclerosis And Obesity, Congqing Wu

Theses and Dissertations--Nutritional Sciences

Angiotensinogen is the only known precursor in the renin-angiotensin system, a hormonal system best known as an essential regulator of blood pressure and fluid homeostasis. Angiotensinogen is sequentially cleaved by renin and angiotensin- converting enzyme to generate angiotensin II. As the major effector peptide, angiotensin II mainly function through angiotensin type 1 receptor.

Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and more recently renin inhibitors are widely known as the 3 classic renin-angiotensin system inhibitory drugs against hypertension and atherosclerosis. Here, we developed an array of regents to explore the effects of angiotensinogen inhibition. First, we demonstrated that genetic deficiency of …

Cardiovascular Adenosine Receptors: Expression, Actions And Interactions, John Headrick, Kevin Ashton, Roselyn Rose'meyer, Jason Peart

Kevin Ashton

Intra- and extracellular adenosine levels rise in response to physiological stimuli and with metabolic/energetic perturbations, inflammatory challenge and tissue injury. Extracellular adenosine engages members of the G-protein coupled adenosine receptor (AR) family to mediate generally beneficial acute and adaptive responses within all constituent cells of the heart. In this way the four AR sub-types—A1, A2A, A2B, and A3Rs—regulate myocardial contraction, heart rate and conduction, adrenergic control, coronary vascular tone, cardiac and vascular growth, inflammatory–vascular cell interactions, and cellular stress-resistance, injury and death. The AR sub-types exert both distinct and overlapping effects, and may interact in mediating these cardiovascular responses. The …

Regulation Of Lipid Homeostasis, Inflammatory Signalling And Atherosclerosis By The Peroxisome Proliferator-Activated Receptor Delta, Lazar A. Bojic

Electronic Thesis and Dissertation Repository

The peroxisome proliferator-activated receptor (PPAR) δ is a ligand-dependent transcription factor that has been implicated in metabolic and inflammatory regulation. The molecular and physiological mechanisms by which PPARδ activation regulates lipid metabolism, inflammatory signaling and protection from atherosclerosis in states of metabolic disturbance such as insulin resistance and dyslipidemia, were investigated in a series of in vitro and in vivo studies. In vitro experiments demonstrated that PPARδ activation inhibits atherogenic lipoprotein-induced lipid accumulation and the associated proinflammatory responses. The primary mechanisms for these effects were increased fatty acid β-oxidation, decreased lipoprotein lipase (LPL) activity, reduced MAPK signaling and improved insulin …

Inflammatory Biomarkers And Subclinical Atherosclerosis In African-American Women With Systemic Lupus Erythematosus (Sle), Edith Williams, Carlos Crespo, Joan Dorn

Journal of Health Disparities Research and Practice

Women with lupus are at increased risk for developing cardiovascular disease (CVD). Previous studies of atherosclerosis in SLE have not been representative of the minority groups most affected by lupus and its complications. Therefore, a study of 41 lupus cases and 83 controls was conducted to investigate the relationship between carotid atherosclerosis and inflammation in African-American women. Participation consisted of a questionnaire, physical examination, fasting blood draw, and ultrasound of the carotid arteries. There were observed differences between cases and controls with regard to carotid intima media thickness (IMT) and traditional cardiovascular risk factors, although few reached statistical significance. Tumor …

Three-Dimensional Ultrasound Measurements Of Carotid Atherosclerosis In Vulnerable Patient Populations, Daniel N. Buchanan

Electronic Thesis and Dissertation Repository

Atherosclerosis is a progressive disease that leads to plaque development and is associated with cardiovascular events such as myocardial infarction and stroke. Several biomarkers have been established as surrogates of plaque development yet none can provide direct, noninvasive, rapid measurements of atherosclerotic disease. Three-dimensional Ultrasound (3DUS) image acquisition is safe, inexpensive and fast, however 3DUS image measurements are limited due to time consuming manual image analyses. In addition, the true clinical meaning of 3DUS carotid imaging measurements has not yet been established. A semi-automated approach for the estimation of 3DUS Total Plaque Volume (TPV) was developed with similar variability and …

Characterization Of The Mechanism Of Pparγ-Mediated Neointima Formation In Rodents, Ryoko Tsukahara

Theses and Dissertations (ETD)

Lysophosphatidic acid (LPA) and its ether analog alkyl glycerophosphate (AGP) elicit arterial wall remodeling when applied intralumenally into the uninjured carotid artery. LPA is the ligand of eight GPCRs and the peroxisome proliferator-activated receptor γ (PPARγ). We pursued a gene knockout strategy to identify the LPA receptor subtypes necessary for the neointimal response in a non-injury model of carotid remodeling and also compared the effects of AGP and the PPARγ agonist rosiglitazone (ROSI) on balloon injury-elicited neointima development. In the balloon injury model AGP significantly increased neointima; however, rosiglitazone application attenuated it. AGP and ROSI were also applied intralumenally for …

Autoimmune Responses To Atherosclerotic Lipids: A Study In Murine Models Of Atherosclerosis And Obesity, Hanjing Wu

Dissertations & Theses (Open Access)

Atherosclerosis is a chronic, complex arterial disease characterized by intimal lipid accumulation and inflammation. A unique lipid-binding molecule, namely cluster of differentiation 1d (CD1d), may impact atherosclerosis. Structurally, CD1d acts as a nonpolymorphic cell-surface receptor, resembling the major histocompatibility complex-I (MHC-I). While MHC-I restricts peptide antigen presentation to T cells, CD1d presents lipid antigens to T cells named CD1d-restrictedd T cells. Although increased expression of CD1d has been found in human plaques, the exact nature of CD1d-recognized lipids in atherosclerosis remains to be determined. Three groups of lipids may undergo oxidation in atherosclerosis producing atherogenic lipids: phospholipids, fatty acids, and …

Atherosclerosis And Antioxidants, Yehoshua Lewis

The Science Journal of the Lander College of Arts and Sciences

Cellular lipid oxidation is a known cause for the cascade leading to the formation of lipid laden foam cells, which can cause of atherosclerosis. While statins and antioxidants have recently come under question in the amelioration of atherosclerosis, Flavonoids have recently been touted as a powerful antioxidant and suppresser of atherosclerosis. This paper will attempt to show why statins and vitamin E have come under scrutiny, and how the desired effects of Flavonoids can be attributed to the role it plays in increased paraoxonase-1 activity (a known anti inflammatory associated with HDL), decreased C- Reactive protein activity, and increased nitric …

Inflammatory Biomarkers And Subclinical Atherosclerosis In African-American Women With Systemic Lupus Erythematosus (Sle), Edith M. Williams, Carlos J. Crespo, Joan Dorn

Community Health Faculty Publications and Presentations

Women with lupus are at increased risk for developing cardiovascular disease (CVD). Previous studies of atherosclerosis in SLE have not been representative of the minority groups most affected by lupus and its complications. Therefore, a study of 41 lupus cases and 83 controls was conducted to investigate the relationship between carotid atherosclerosis and inflammation in African-American women. Participation consisted of a questionnaire, physical examination, fasting blood draw, and ultrasound of the carotid arteries. There were observed differences between cases and controls with regard to carotid intima media thickness (IMT) and traditional cardiovascular risk factors, although few reached statistical significance. Tumor …