Lipids and atherosclerosis

Abstract

Atherosclerosis is the leading cause of death in North America and within the next two decades will be the leading cause worldwide. Atherosclerosis is characterized by vascular obstruction from the deposits of plaque, resulting in reduced blood flow. Plaque rupture and the consequent thrombosis may lead to sudden blockage of the arteries and cause heart attack. High serum lipid levels, especially the elevated level of low-density lipoprotein (LDL), have been shown to be strongly related to the development of atherosclerosis. It is generally accepted that atherosclerotic lesions are initiated via an enhancement of LDL uptake by monocytes and macrophages. In the liver, uptake of plasma LDL is mediated via specific LDL receptors, but a scavenger receptor system is employed by macrophages. Plasma LDL must be modified prior to uptake by macrophages. Analysis of the lipid content in the oxidatively modified LDL from hyper lipidemic patients revealed that the level of lysophosphatidylcholine was greatly elevated, and the high level of the lysolipid was shown to impair the endothelium-dependent relaxation of the blood vessels. In a separate study, we showed that a high level of homocysteine caused the increase in cholesterol production and apolipoprotein B-100 secretion in hepatic cells. Statins have been used effectively to control the production of cholesterol in the liver, and recently, ezetimibe has been shown to supplement the efficacy of statins by inhibiting cholesterol absorption. The factor of elevated levels of triglyceride-rich lipoproteins in association with depressed high-density lipoproteins, usually in the context of insulin resistance, is an important contributor to atherosclerosis and can be effectively treated with fibric acid derivatives. In hyperhomocysteinemia, folic acid supplements may have a role in the control of cholesterol by reducing the plasma homocysteine level.

Assessment of Carotid Plaque Vulnerability Using Structural and Geometrical Determinants

“…1 This is potentially preventable by carotid revascularization techniques, and the degree of luminal stenosis is commonly used in clinical practice as an indicator for carotid endarterectomy or carotid artery angioplasty/stenting. Carotid endarterectomy has been shown to be beneficial in patients with symptomatic high-grade (70-99%) stenosis, 2,3 but it is more difficult to draw conclusions about possible benefits for patients with moderate carotid stenosis.…”

Mutations of a Drosophila NPC1 Gene Confer Sterol and Ecdysone Metabolic Defects

“…While sterols are essential due to the important biological functions they serve, an overabundance of the primary mammalian sterol, cholesterol, is toxic and contributes to a variety of prevalent diseases including heart disease and stroke (Choy et al 2004;Saini et al 2004). Accumulating evidence also suggests that alterations in cholesterol homeostasis may contribute to neurodegenerative disorders such as Alzheimer's disease, although the mechanisms by which alterations in cholesterol metabolism affect neuronal integrity remain unclear (Burns and Duff 2002;Reiss et al 2004;Wellington 2004).…”

Association of APOA1 gene polymorphisms (rs670, rs5069, and rs2070665) with dyslipidemia in the Kazakhs of Xinjiang

“…Although it is well known that the reason for dyslipidemia is the interactions of multiple environmental and genetic factors (Choy et al, 2004;Yamada et al, 2007), the underlying mechanisms remain poorly understood. Pagani et al (1990) reported a common MspI enzyme site 75 bp upstream from the initiating transcription site of the human apolipoprotein A1 (APOA1) gene.…”