Cardiovascular diseases are the greatest cause of morbidity and mortality in the Western world and elevations of serum lipids and lipoproteins have been established as a major risk factor for atherosclerosis. The risk for developing atherosclerosis increases as the total serum cholesterol increases whereas elevation of HDL has been associated with a decreased risk of this disease. Many studies have proven that the diet profoundly affects these factors. Thus, attention has focused on the diet, not only as a likely major contributing factor to the variability in atherosclerosis incidence, but more importantly as a readily modifiable factor. Dietary manipulation is not only recommended as the first line of treatment in hyperlipidemia, but also as an important measure for the population at large. Nevertheless, many important aspects of the relationship between diet and lipid levels remain unclear. We propose to evaluate the effect of several of the currently recommended dietary regimens on lipoprotein metabolism. A more complete knowledge of this subject is important, especially as it relates to dietary effects on lipoprotein metabolism and lipoprotein-related enzymes as well as heritability of plasma lipoproteins and response to dietary manipulations. Lipoprotein metabolism can be conveniently, yet intensively, studied by injecting radiolabeled HDL, LDL, or VLDL into the blood stream and then carefully measuring its disappearance from the blood, along with the excretion of radioactive iodine as a breakdown product in the urine. These studies can extend our understanding of lipoprotein metabolism in directions that may provide a basis for more effective treatment, or even prevention, of atherosclerosis. To address some of these issues we are also recruiting identical (MZ) and fraternal (DZ) twins to estimate the extent of genetic control of many different phenotypes in humans. In twin studies, the difference in pair similarity between MZ and DZ twins indicates how much of the phenotype in genetically controlled.
We aim to study lipoprotein levels and related parameters in MZ and DZ pairs on low and high fat diets under metabolic ward conditions to estimate the genetic control of lipoprotein levels on a fixed diet and the genetic control of diet response. Body composition studies include the use of DPX (Dual photon absorptiometry), which measures body bone mass and whole body bone density utilizing an x-ray source adding information on fat distribution. DPX and other body composition studies might explain in part the differences in lipoprotein levels not accounted for the genetic background Lipolytic enzymes play an important role in lipoprotein metabolism which, in turn, appears to play a crucial role in the development of atherosclerosis. In studying the factors which influence lipoprotein levels and metabolism, it is frequently desirable to measure body lipolytic activity concurrently with other lipoprotein parameters. The two most important lipolytic enzymes are lipoprotein lipase (LPL) and hepatic endothelial lipase (HL), each of which is believed to determine in part the levels of the triglyceride-rich lipoproteins and high-density lipoproteins (HDL). Both of these enzymes normally do not circulate in the plasma, but are bound to the endothelial cells which line the blood vessels of the body. In order to study the activity of these enzymes in human subjects, it is necessary either to biopsy the appropriate organ or to release the enzymes from the vessel wall into the circulation and then sample the blood. Heparin is chemically similar to the portion of these enzymes that bind to the vessel wall. When injected briefly, heparin then competes for that binding and releases most of LPL and HL into the blood. An appropriately timed blood sample can then be assayed in vitro for lipolytic activity of each of the enzymes by relatively simple techniques.
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