Health Effects of Lipids Part2

Atherosclerosis

Atherosclerosis involves the gradual narrowing of arteries due to the build-up of plaque. It takes years to develop and happens insidiously without people noticing it. Clinical problems develop when the obstruction is such that blood flow, and thus oxygen supply, cannot meet demands.The low oxygen supply leads to a condition called ischemia, explaining the term ischemic heart disease.Atherosclerosis occurs in many parts of the body. In the heart it may lead to ischemic heart disease, in the brain it may lead to stroke, and in areas outside the brain and heart to peripheral vascular disease also called peripheral artery disease.

Pathogenesis of atherosclerosis

The normal artery contains three layers.The inner layer is called the endothelium or intima and is in direct contact with the blood. The middle layer contains smooth muscle cells that allow blood vessels to expand or contract. The outer layer of arteries is composed mostly of connective tissue. It is commonly thought that a plaque begins to form because the endothelium becomes damaged, possibly because of elevated lipid levels in the blood, high blood pressure, or smoking. The damage causes white blood cells to stick to the endothelium. What happens is that the endothelium produces sticky molecules called adhesion molecules that capture the white blood cells.After adhesion to the endothelium, the white blood cell moves inside the wall of the artery. White blood cells that move into the blood vessel wall include T-cells and macrophages.In the vessel wall, macrophages take up lipid and become foam cells. This causes the vessel wall to gradually thicken as it fills up with lipid. As the atherosclerotic process advances, smooth muscle cells move into the intima and produce molecules such as collagen, that give the inner wall a connective tissue-like appearance.  In advancing lesions, cells die and cell debris including lipids accumulates in the central region of the plaque, called the lipid or necrotic core.It is believed that the lipids that accumulate in the atherosclerotic plaque primarily originate from LDL, which is able to penetrate the wall of the artery and become scavenged by macrophages. In turn, the macrophages become foam cells and start to produce molecules that aggravate the inflammation.

The two key in the initiation of atherosclerosis are 1)Adhesion and infiltration of immune cells into the vascular wall; 2) Entry of LDL particles into the vascular wall and formation of foam cells.The idea that lipids, especially cholesterol, are deposited in atherosclerotic lesions goes back more than 60 years, and led to the suggestion that atherosclerosis may be linked to elevated blood cholesterol. However, in the ensuing years, the hypothesis that high blood cholesterol levels contribute causally to atherosclerosis and CHD (the “lipid hypothesis”)  faced huge skepticism Even today certain groups of individuals remain in denial about the importance of (LDL) cholesterol in atherosclerosis. Within the cardiovascular research community there is a strong consensus about the role of lipids in atherosclerosis, particularly LDL. In addition to the role of lipids, there is near universal recognition for an important role of the immune system and inflammation in the development of atherosclerosis, based on experimental, clinical, and epidemiological studies (the “inflammatory hypothesis”). What is still lacking is the proof that anti-inflammatory drug therapy reduces myocardial infarctions ("heart attack"). 

Most atherosclerotic lesions are stable and do not cause any problems. In those cases, the lipid core is covered by a thick layer of materials typically found in connective tissue forming a so called fibrous cap. However, when the lesion is very inflamed, white blood cells produce molecules that gradually break down the fibrous cap. The thinning of the fibrous cap causes the plaque to become unstable and make it prone to rupture. The rupture of the plaque is very dangerous, as it triggers blood clotting (thrombosis). The blood clot can partially or completely occlude the blood vessel at the site of rupture, or it can be dislodged and travel further to block a blood vessel elsewhere.

 

 

 

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