Cardiology Commons^™

Characterization Of Secretory Sphingomyelinase Activity, Lipoprotein Sphingolipid Content And Ldl Aggregation In Ldlr-/- Mice Fed On A High-Fat Diet, Gergana M. Deevska, Manjula Sunkara, Andrew J. Morris, Mariana N. Nikolova‑Karakashian

Physiology Faculty Publications

The propensity of LDLs (low-density lipoproteins) for aggregation and/or oxidation has been linked to their sphingolipid content, specifically the levels of SM (sphingomyelin) and ceramide. To investigate this association in vivo, ldlr (LDL receptor)-null mice (ldlr-/-) were fed on a modified (atherogenic) diet containing saturated fats and cholesterol. The diet led to significantly elevated SM content in all serum lipoproteins. In contrast, ceramide increased only in the LDL particles. MS-based analyses of the lipid acyl chain composition revealed a marked elevation in C16:0 fatty acid in SM and ceramide, consistent with the prevalence of palmitic acid in the modified diet. …

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 …

Stop Atherosclerosis In Native Diabetics Study (Sands): Baseline Characteristics Of The Randomized Cohort, Angela Silverman, Chun-Chih J. Huang, Marie Russell, Mihriye Mete, Mary J. Roman, Mario Stylianou, Elisa T. Lee, Fawn Yeh, Jerome Fleg, Charlton Wilson, Jeffrey A. Henderson, Matthew R. Weir, Robert E. Ratner, Barbara V. Howard

Journal of Health Disparities Research and Practice

Objectives: To present baseline characteristics of American Indians in the Stop Atherosclerosis in Native Diabetics Study (SANDS) and compare them with population-based data from American Indians and other ethnic groups. Design: 499 people with type 2 diabetes ≥ age 40, without known CVD, were recruited for a randomized 3-year trial to evaluate treatment targets for LDL-C (70 vs. 100 mg/dL) and systolic blood pressure (BP) (115 vs. 130 mmHg). Baseline evaluations included physical exam, collection of blood and urine samples, and carotid ultrasound and echocardiographic measures. Results: Mean age was 56 years; 66% were female. Average BMI was 33 kg/m2. …

Chronic Kidney Disease Is Associated With Increased Coronary Artery Atherosclerosis As Revealed By Multidetector Computed Tomographic Angiography, Sion K Roy, Albert Cespedes, Dong Li, Tae-Young Choi, Matthew J Budoff

The Texas Heart Institute Journal

Chronic kidney disease (CKD) is an independent risk factor for cardiovascular events. We evaluated whether multidetector computed tomographic angiography (MDCTA) revealed a link between pre-dialysis CKD and coronary artery atherosclerosis.

We retrospectively analyzed 549 patients who underwent MDCTA. Patients were divided into 3 groups: normal glomerular filtration rate (GFR) (GFR >90 mL/min/1.73 m2 body surface area), mild CKD (>60GFR≤90 mL/min/1.73 m2), and moderate CKD (>30GFR≤60 mL/min/1.73 m2). Normality testing was performed to determine if continuous variables were modeled in Gaussian distribution before analysis of variance was applied. The χ2 test was used to compare GFR subgroups. Multiple linear …

Ghrelin Receptor Deficiency Does Not Affect Diet-Induced Atherosclerosis In Low-Density Lipoprotein Receptor-Null Mice, Kirk M. Habegger, Erin Grant, Paul Thomas Pfluger, Diego Perez-Tilve, Alan Daugherty, Dennis Bruemmer, Matthias H. Tschöp, Susanna M. Hofmann

Saha Cardiovascular Research Center Faculty Publications

OBJECTIVE: Ghrelin, a stomach-derived, secreted peptide, and its receptor (growth hormone secretagogue receptor, GHSR) are known to modulate food intake and energy homeostasis. The ghrelin system is also expressed broadly in cardiovascular tissues. Since ghrelin has been associated with anti-inflammatory and anti-atherogenic properties, but is also well known to promote obesity and impair glucose metabolism, we investigated whether ghrelin has any impact on the development of atherosclerosis. The hypothesis that endogenous ghrelin signaling may be involved in atherosclerosis has not been tested previously.

METHODS AND RESULTS: We crossed ghrelin receptor knockout mice (GHSr^-/-) into a low-density lipoprotein receptor-null …

Micro-Ultrasonographic Imaging Of Atherosclerotic Progression And Correlation With Inflammatory Markers In Apolipoprotein-E Knockout Mice, Rong-Juan Li, Ya Yang, Yan-Hong Wang, Jin-Jie Xie, Li Song, Zheng Wang, Yao-Zhong Zhang, Yan-Wen Qin, Zhi-An Li, Xiao-Shan Zhang

The Texas Heart Institute Journal

We studied prospectively whether atherosclerotic progression in apolipoprotein-E knockout mice could be noninvasively and accurately measured by use of high-resolution ultrasonographic biomicroscopy. We examined the correlation between the ultrasonographic characterization of ascending aortic atherosclerotic plaque and plasma C-reactive protein, interleukin-1, and interleukin-6 levels in these mice.

In 4 age groups (8, 16, 24, and 32 wk) of 8 male knockout mice each (atherosclerotic groups) and age-matched male C57BL/6 mice (control groups), we used ultrasonographic biomicroscopy to measure maximal plaque thickness or intima-media thickness in the ascending aorta. We compared the findings with corresponding histologic measurements, and we measured plasma C-reactive …

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 …

Renin Inhibition Reduces Hypercholesterolemia-Induced Atherosclerosis In Mice, Hong Lu, Debra L. Rateri, David L. Feldman, Richard Charnigo, Akiyoshi Fukamizu, Junji Ishida, Elizabeth Grace Oesterling, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

The role of the renin angiotensin system (RAS) in atherosclerosis is complex because of the involvement of multiple peptides and receptors. Renin is the rate-limiting enzyme in the production of all angiotensin peptides. To determine the effects of renin inhibition on atherosclerosis, we administered the novel renin inhibitor aliskiren over a broad dose range to fat-fed LDL receptor-deficient (Ldlr^-/-) mice. Renin inhibition resulted in striking reductions of atherosclerotic lesion size in both the aortic arch and the root. Subsequent studies demonstrated that cultured macrophages expressed all components of the RAS. To determine the role of macrophage-derived angiotensin in …

Novel Implications Of The Kallikrein-Kinin System In Diabetic Vasculopathy: A Proposed Role Of Prekallikrein In The Causation And Development Of Vascular Pathology In Diabetics, Rany Abdallah

MUSC Theses and Dissertations

Despite the clear association between diabetes and atherosclerotic vascular disease, the factors and mechanisms underlying the association between the two diseases are not well understood. Our preliminary studies, based on data obtained from the national Diabetes Control and Complication Trial/Epidemiology of Diabetes and Complications (DCCT/EDIC) cohort of type 1 diabetes subjects, suggest that diabetic atherosclerosis is linked to defects in the Kallikrein-Kinin System (KKS). Our research also found that apoliporotein E (ApoE) knockout mice, which have marked increase in total plasma cholesterol levels and a higher number of atherosclerotic lesions compared to wild type mice, have markedly higher plasma prekallikrein …

Regulation Of Acetylated Low Density Lipoprotein Uptake In Macrophages By Pertussis Toxin-Sensitive G Proteins, Stewart C. Whitman, Alan Daugherty, Steven R. Post

Gill Heart & Vascular Institute Faculty Publications

Class A scavenger receptors (SR-A) mediate the uptake of modified low density lipoprotein (LDL) by macrophages. Although not typically associated with the activation of intracellular signaling cascades, results with peritoneal macrophages indicate that the SR-A ligand acetylated LDL (AcLDL) promotes activation of cytosolic kinases and phospholipases. These signaling responses were blocked by the treatment of cells with pertussis toxin (PTX) indicating that SR-A activates G_i/o-linked signaling pathways. The functional significance of SR-A-mediated G_i/o activation is not clear. In this study, we investigated the potential role of G_i/o activation in regulating SR-A-mediated lipoprotein uptake. Treatment of mouse …