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.
Related Posts : Atherosclerosis,
narrowing of arteries,
peripheral artery disease.ischemic heart disease,
peripheral vascular disease