Atherosclerosis and lipoproteins The atherosclerotic process is not well understood. Atherosclerosis is associated with inflammatory processes in the endothelial cells of the vessel wall associated with retained low-density lipoprotein (LDL) particles. This retention may be a cause, an effect, or both, of the underlying inflammatory process. The presence of the plaque induces the muscle cells of the blood vessel to stretch, compensating for the additional bulk. The endothelial lining then thickens, increasing the separation between the plaque and lumen. The thickening somewhat offsets the narrowing caused by the growth of the plaque, but moreover, it causes the wall to stiffen and become less compliant to stretching with each heartbeat. Modifiable * Western pattern diet * Abdominal obesity * Insulin resistance * Diabetes * Dyslipidemia * Hypertension * Trans fat * Tobacco smoking * Bacterial infections * HIV/AIDS Nonmodifiable * South Asian descent * Advanced age * Genetic abnormalities * Family history *<unk>  anatomy and branch pattern Lesser or uncertain * Thrombophilia * Saturated fat * Excessive carbohydrates * Elevated triglycerides * Systemic inflammation * Hyperinsulinemia * Sleep deprivation * Air pollution * Sedentary lifestyle * Arsenic poisoning * Alcohol * Chronic stress * Hypothyroidism * Periodontal disease Dietary The relation between dietary fat and atherosclerosis is controversial. The USDA, in its food pyramid, promotes a diet of about 64% carbohydrates from total calories. The American Heart Association, the American Diabetes Association and the National Cholesterol Education Program make similar recommendations. In contrast, Prof Walter Willett (Harvard School of Public Health, PI of the second Nurses' Health Study) recommends much higher levels of fat, especially of monounsaturated and polyunsaturated fat. These dietary recommendations reach a consensus, though, against consumption of trans fats. The role of eating oxidized fats (rancid fats) in humans is not clear. Rabbits fed rancid fats develop atherosclerosis faster. Rats fed DHA-containing oils experienced marked disruptions to their antioxidant systems, and accumulated significant amounts of phospholipid hydroperoxide in their blood, livers and kidneys. Rabbits fed atherogenic diets containing various oils were found to undergo the most oxidative susceptibility of LDL via polyunsaturated oils. In another study, rabbits fed heated soybean oil "grossly induced atherosclerosis and marked liver damage were histologically and clinically demonstrated." However, Fred Kummerow claims that it is not dietary cholesterol, but oxysterols, or oxidized cholesterols, from fried foods and smoking, that are the culprit. Rancid fats and oils taste very unpleasant in even small amounts, so people avoid eating them. It is very difficult to measure or estimate the actual human consumption of these substances. Highly unsaturated omega-3 rich oils such as fish oil, when being sold in pill form, can hide the taste of oxidized or rancid fat that might be present. In the US, the health food industry's dietary supplements are self-regulated and outside of FDA regulations. To properly protect unsaturated fats from oxidation, it is best to keep them cool and in oxygen-free environments. Pathophysiology Atherogenesis is the developmental process of atheromatous plaques. It is characterized by a remodeling of arteries 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 arterial 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 artery lumen in cardiac muscle. The ensuing inflammation leads to the formation of atheromatous plaques in the arterial 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. Cellular Micrograph of an artery that supplies the heart showing significant atherosclerosis and marked luminal narrowing. Tissue has been stained using Masson's trichrome. 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 further activation into monocyte-derived macrophages. The primary documented driver of this process is oxidized lipoprotein particles 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) particles 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 artery 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 further 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 and lipids 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 portion of the atheromatous plaques. With the atheromatous plaque interfering with the regulation of the calcium deposition, it accumulates and crystallizes. A similar form of intramural calcification, presenting the picture of an early phase of arteriosclerosis, appears to be induced by many 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) particles. To attract and stimulate macrophages, the cholesterol must be released from the LDL particles and oxidized, a key step in the ongoing inflammatory process. The process is worsened if it is insufficient high-density lipoprotein (HDL), the lipoprotein particle 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 artery lining (the intima). These capped fatty deposits (now called 'atheromas') produce enzymes that cause the artery to enlarge over time. As long as the artery enlarges sufficiently to compensate for the extra thickness of the atheroma, then no narrowing ("stenosis") of the opening ("lumen") occurs. The artery becomes expanded with an egg-shaped cross-section, still with a circular opening. If the enlargement is beyond proportion to the atheroma thickness, then an<unk>  is created. Visible features Severe atherosclerosis of the aorta. Autopsy specimen. Although arteries are not typically studied microscopically, two plaque types can be distinguished: # The fibro-lipid (fibro-fatty) plaque is characterized by an accumulation of lipid-laden cells underneath the intima of the arteries, typically without narrowing the lumen due to compensatory expansion of the bounding muscular layer of the artery wall. Beneath the endothelium, there is a "fibrous cap" covering the atheromatous "core" of the plaque. The core consists of lipid-laden cells (macrophages and smooth muscle cells) with elevated tissue cholesterol and cholesterol ester content, fibrin, proteoglycans, collagen, elastin, and cellular debris. In advanced plaques, the central core of the plaque usually contains extracellular cholesterol deposits (released from dead cells), which form areas of cholesterol crystals with empty, needle-like clefts. At the periphery of the plaque are younger "foamy" cells and capillaries. These plaques usually produce the most damage to the individual when they rupture. Cholesterol crystals may also play a role. # The fibrous plaque is also localized under the intima, within the wall of the artery resulting in thickening and expansion of the wall and, sometimes, spotty localized narrowing of the lumen with some atrophy of the muscular layer. The fibrous plaque contains collagen fibers (eosinophilic), precipitates of calcium (hematoxylinophilic), and rarely, lipid-laden cells. In effect, the muscular portion of the artery wall forms small<unk> s just large enough to hold the atheroma that are present. The muscular portion of artery walls usually remains strong, even after they have
medical cause of Coronary artery aneurysm
medical cause of Coronary artery disease
complications of Coronary thrombosis
medical cause of Dilated cardiomyopathy
medical cause of Myocardial infarction
complications of Aortic aneurysm
medical cause of Peripheral artery disease
medical cause of Myocarditis