Which of the following about atherosclerosis is true?
Atherogenesis is the developmental process of atheromatous plaques. It is characterized by a remodeling of aeries leading to subendothelial accumulation of fatty substances called plaques. The buildup of an atheromatous plaque is a slow process, developed over a period of several years through a complex series of cellular events occurring within the aerial wall and in response to a variety of local vascular circulating factors. One recent hypothesis suggests that, for unknown reasons, leukocytes, such as monocytes or basophils, begin to attack the endothelium of the aery lumen in cardiac muscle. The ensuing inflammation leads to formation of atheromatous plaques in the aerial tunica intima, a region of the vessel wall located between the endothelium and the tunica media. The bulk of these lesions is made of excess fat, collagen, and elastin. At first, as the plaques grow, only wall thickening occurs without any narrowing. Stenosis is a late event, which may never occur and is often the result of repeated plaque rupture and healing responses, not just the atherosclerotic process by itself. Early atherogenesis is characterized by the adherence of blood circulating monocytes (a type of white blood cell) to the vascular bed lining, the endothelium, then by their migration to the sub-endothelial space, and fuher activation into monocyte-derived macrophages. The primary documented driver of this process is oxidized lipoprotein paicles within the wall, beneath the endothelial cells, though upper normal or elevated concentrations of blood glucose also plays a major role and not all factors are fully understood. Fatty streaks may appear and disappear. Low-density lipoprotein (LDL) paicles in blood plasma invade the endothelium and become oxidized, creating risk of cardiovascular disease. A complex set of biochemical reactions regulates the oxidation of LDL, involving enzymes (such as Lp-LpA2) and free radicals in the endothelium. Initial damage to the endothelium results in an inflammatory response. Monocytes enter the aery wall from the bloodstream, with platelets adhering to the area of insult. This may be promoted by redox signaling induction of factors such as VCAM-1, which recruit circulating monocytes, and M-CSF, which is selectively required for the differentiation of monocytes to macrophages. The monocytes differentiate into macrophages, which proliferate locally, ingest oxidized LDL, slowly turning into large "foam cells" - so-called because of their changed appearance resulting from the numerous internal cytoplasmic vesicles and resulting high lipid content. Under the microscope, the lesion now appears as a fatty streak. Foam cells eventually die and fuher propagate the inflammatory process. In addition to these cellular activities, there is also smooth muscle proliferation and migration from the tunica media into the intima in response to cytokines secreted by damaged endothelial cells. This causes the formation of a fibrous capsule covering the fatty streak. Intact endothelium can prevent this smooth muscle proliferation by releasing nitric oxide. Calcification forms among vascular smooth muscle cells of the surrounding muscular layer, specifically in the muscle cells adjacent to atheromas and on the surface of atheroma plaques and tissue. In time, as cells die, this leads to extracellular calcium deposits between the muscular wall and outer poion of the atheromatous plaques. With the atheromatous plaque interfering with the regulation of the calcium deposition, it accumulates and crystallizes. A similar form of an intramural calcification, presenting the picture of an early phase of aeriosclerosis, appears to be induced by a number of drugs that have an antiproliferative mechanism of action (Rainer Liedtke 2008). Cholesterol is delivered into the vessel wall by cholesterol-containing low-density lipoprotein (LDL) paicles. To attract and stimulate macrophages, the cholesterol must be released from the LDL paicles and oxidized, a key step in the ongoing inflammatory process. The process is worsened if there is insufficient high-density lipoprotein (HDL), the lipoprotein paicle that removes cholesterol from tissues and carries it back to the liver. The foam cells and platelets encourage the migration and proliferation of smooth muscle cells, which in turn ingest lipids, become replaced by collagen and transform into foam cells themselves. A protective fibrous cap normally forms between the fatty deposits and the aery lining (the intima). These capped fatty deposits (now called 'atheromas') produce enzymes that cause the aery to enlarge over time. As long as the aery enlarges sufficiently to compensate for the extra thickness of the atheroma, then no narrowing ("stenosis") of the opening ("lumen") occurs. The aery becomes expanded with an egg-shaped cross-section, still with a circular opening. If the enlargement is beyond propoion to the atheroma thickness, then an aneurysm is created Ref Davidson 23rd edition pg 456
Intake of unsaturated fatty acid associated with decreased risk
Thoracic aoa involvement is more "Severe than abdominal aoa involvement
Extent of lesion in veins is same as that in aeries
Hypercholesterolemia does not always increase the risk of atherosclerosis per se
C.V.S