Track topics on Twitter Track topics that are important to you
To determine the role of genetic factors in predicting resistance and susceptibility to coronary artery disease.
Coronary artery disease appears to be a consequence of the interaction between an individual's genotype and exposure to environmental factors. Genetic information has the potential to contribute to the identification of families and individuals with a biological predisposition for developing coronary artery disease. Although numerous studies have suggested the possibility of a link between polymorphic genetic variation and coronary heart disease, it has not been possible to use any single genetic locus or combination of loci to establish a person's risk except for the case of familial hypercholesterolemia.
Apolipoproteins play a critical role in regulating cellular uptake of lipoproteins by specific receptors, regulating the activities of lipoprotein lipase and lecithin-cholesterol acyl transferase, and in the indirect regulation of the intracellular enzymes, acyl-cholesterol acyl transferase and HMG Co-A reductase. This study provided insight into the role of environmental and genetic effects on phenotypic variation of the individual components of the molecules of lipid metabolism as well as on the relationships between components.
Previous studies conducted under this grant include: the relationship between quantitative levels of apo A-I and coronary artery disease as defined by coronary angiography; the effects of exercise, alcohol, obesity, and pregnancy on apo A-I levels; the relationship between apo A-I and HDL levels in children and the mode of inheritance of apo A-I levels in pedigrees in the Rochester, Minnesota community; and characterization of the antigenic structure of apolipoproteins in coronary artery disease.
Subjects for the study were drawn from the Rochester Family Heart Study which initiated recruitment for the family study in January 1985. In 31 months of recruitment, 443 households were contacted and 300 agreed to participate. In August 1987 all individuals identified by these households had completed their clinic visits providing 1,999 physical exams. The 300 households yielded 276 three and four generation pedigrees with 593 parents, 598 grandparents, 14 great-grandparents, and 854 children. Disease information was obtained from medical records for an additional 400 grandparents. In 1988 an additional 2,100 individual members of 300 families were surveyed.
Medical records and death certificates were reviewed to evaluate coronary artery disease endpoints in all adults members of the pedigrees. Clinical data collected included: a history of symptoms of coronary artery disease, arteriosclerosis obliterans, cerebrovascular disease or surgery for these diseases; smoking; medication; history of genetic relationships. Measurements were made of cholesterol, triglycerides, HDL and LDL cholesterol, apo A-I, apo A-II, apo E, apo C-III, apo C-II, apo B, apo Lp(a), LDL apo B, HDL apo E, and DNA extraction. Lipid, lipoprotein, and apolipoprotein phenotypes and the restriction fragment length polymorphisms (RFLP) were measured in candidate genes for coronary artery disease. Genetic and phenotype analyses were conducted at the University of Michigan. The RFLP and apolipoprotein isotyping analyses were conducted at the University of Pittsburgh. RFLP analysis and LDL receptor and A-I gene analysis were conducted at Charing Cross Medical Center in London, England.
Observational Model: Natural History
National Heart, Lung, and Blood Institute (NHLBI)
Published on BioPortfolio: 2014-08-27T03:58:00-0400
To determine the factors associated with progression of sub-clinical atherosclerosis and to evaluate the associations between the progression of sub-clinical atherosclerosis and the develo...
Atherosclerosis vaccine, V6, has been through two small-scale Phase II open label clinical trials. It has shown significant improvement in lipid profile in patients with overweight or obes...
To evaluate common genetic variations, that in combination with exposure to tobacco smoke, may modify the risk of atherosclerosis.
To measure by gas-liquid chromatography the relative concentrations of all saturated and unsaturated fatty acids found in the cholesterol ester and phospholipid fractions of plasma from 4,...
The purpose of this study is to determine the effects of estrogen replacement therapy (ERT) on the progression of early atherosclerosis in healthy postmenopausal women without preexisting ...
Matrix metalloproteinases (MMPs) have been implicated in atherosclerosis and vascular calcification. Among them, we reported that MMP10 is present in human atheroma, associated with atherosclerosis. H...
Progranulin is a circulating protein that modulates inflammation and is found in atherosclerotic lesions. Here we determined whether inflammatory cell-derived progranulin impacts atherosclerosis devel...
The development of atherosclerosis is tightly regulated by the innate and adaptive immune system. Communication between these two compartments occurs, among others, upon presentation of lipid antigens...
Atherosclerosis is critically fueled by vascular inflammation through oxidized lipids and inflammatory cytokines such as tumor necrosis factor (TNF)-α. Genetic disruption of Tnf-α reduces atheroscle...
The purpose of this review was to examine the role of IL-1β in the inflammatory process central to the development of atherosclerosis and to discuss current clinical evidence for treatments targeting...
Lack of perfusion in the EXTREMITIES resulting from atherosclerosis. It is characterized by INTERMITTENT CLAUDICATION, and an ANKLE BRACHIAL INDEX of 0.9 or less.
Complete blockage of blood flow through one of the CORONARY ARTERIES, usually from CORONARY ATHEROSCLEROSIS.
A drug that has been given by mouth in the treatment of atherosclerosis and other vascular disorders, hyperlipidemias, and thrombo-embolic disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1408)
Strains of mice that contain genetic disruptions (knockout) of APOLIPOPROTEINS E genes. They are used as models for ATHEROSCLEROSIS research.
A measurement of the thickness of the carotid artery walls. It is measured by B-mode ULTRASONOGRAPHY and is used as a surrogate marker for ATHEROSCLEROSIS.
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...
Cardiovascular disease (CVD)
Acute Coronary Syndromes (ACS) Blood Cardiovascular Dialysis Hypertension Stent Stroke Vascular Cardiovascular disease (CVD) includes all the diseases of the heart and circulation including coronary heart disease (angina...