Pathophysiology
Atherosclerosis is a
disease characterized by the buildup of fatty streaks within the arterial
tree. This disease sets its roots when
an accumulation of atherosclerotic plaque, primarily consisting of lipids,
inflammatory and smooth muscle cells, and the matrix of connective tissue,
forms. Ironically, this disease begins
to form when the body sends an inflammatory response to injury or destruction
of the endothelial layer of the artery. While
atherosclerosis can develop in any area within the arterial tree, certain areas
are more prevalent. For instance, in areas
where the arterial tree branches, endothelial dysfunction is likely, which in
turn, stops endothelial production of nitric oxide. Nitric oxide is a vasodilator and
anti-inflammatory molecule that plays a large role in maintaining the tone of the
endothelium of arteries.
Further, in areas of a diminished blood flow,
the endothelial cells are less likely to produce adhesion molecules; these
molecules are tasked with finding and binding inflammatory cells, so when they
aren’t present, inflammation is more likely to occur. Certain risk factors are also known for
inhibiting nitric oxide production, as well as stimulating the production of
certain molecules, cytokines, proteins and other elements that are detrimental
to the arteries. Essentially, this will
result in the endothelial binding of monocytes and T cells. As these cells flow into the subendothelial
space, a local vascular inflammatory response is at stake. Eventually, the monocytes in the endothelium
are transformed into macrophages. Passing
lipids such as low-density lipoproteins (LDL), bind to the endothelial cells
and are oxidized. Oxidation of these
lipids and macrophages produce foam cells, resulting in the initial stages of
atherosclerosis.
As atherosclerosis
develops, the plaque can be either stable or unstable. On one hand, stable plaque can disappear,
remain static, or continue to grow until occlusion or stenosis occurs. On the other hand, unstable plaque increases
chances for thrombosis which can lead to infarction.
Unstable plaque is
formed when the integrity of a layer of fibrous connective tissue called the
fibrous cap, is tested. Certain enzymes
are activated by macrophages in the plaque and will eventually consume the
fibrous cap, ultimately weakening its structure and causing a rupture. Ensuing
the rupture, plaque roams freely in the blood stream, and thrombosis is likely.
Risk Factors
There are many risk
factors for atherosclerosis: many of these factors tend to demonstrate
association with the metabolic syndrome.
Certain related factors with metabolic syndrome include abdominal obesity,
atherogenic dyslipidemia, hypertension, insulin resistance, aprothrombotic
state and a proinflammatory state.
However, there are many other factors that can and do play a role in
atherosclerosis. Below is a link that
lists and describes many issues and diseases as they relate to atherosclerosis.
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