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Atherosclerosis is the most common vascular disease. It is the main cause of death of approximately 60% of people in the developed world. The word atherosclerosis is derived from the Greek athere (porridge) and scleros (hardness).
Atherosclerosis is a disease that affects medium to large arteries. Its predilection for branches and bends has become better understood from flow modeling. High shear laminar flow, such as at the external curvature or medial flow divider is protective. In contrast, at the lateral walls (modeled best at the carotid bifurcation), shear is low at best and often becomes turbulent or non-laminar, producing oscillating vectors of shear stress. This area of research was pioneered by Glagov in the 1980s and recently its molecular mechanism has been worked out in greater detail.
Atherosclerosis is the main cause of ischaemic coronary heart disease, carotid artery stenosis by occlusion or thromboembolism. In turn, this can cause ischaemia in the cerebral arteries, presenting either as transient ischaemic attack or cerebral infarction. Abdominal aortic atherosclerotic aneurysms, where the main artery in the abdomen becomes abnormally wide with a thin wall, can burst. Peripheral vascular disease (PVD), which causes intermittent claudication or gangrene of the extremities and pain in the legs when walking, can be relieved by rest.
Coronary thrombosis is typically due to plaque rupture. In this process, the atherosclerotic lesion (abnormal area of artery) has a thin fibrous lining that is more mechanically weak, has increased macrophage cells, and has reduced vascular smooth muscle cells (which normally make collagen).
In plaque rupture, the plaque inflammation erodes the fibrous lining (fibrous cap) to the point where it breaks apart (possibly under added hemodynamic stresses), releasing necrotic debris containing tissue factor in the lipid necrotic core into contact with blood. This stimulates clotting that blocks off the artery (occlusive thrombus). Unless reopened (see reperfusion) by drugs or percutaneous coronary intervention (PTCA, also known as percutaneous coronary intervention PCI) the blocked artery causes the heart muscle to die of lack of nutrients and oxygen. This is termed a myocardial infarction.
The major modifiable atherosclerotic risk factors include smoking, hypertension, hyperlipidemia, diabetes, and obesity, a mild but common independent risk factor which can itself also contribute to the development of hypertension, hyperlipidemia, and diabetes.
Theories of the processes behind atherosclerosis (atherogenesis) have been modified over the years. The German pathologist Rudolf Virchow (1852) foresaw much recent development, theorizing that atherosclerosis was caused by the accumulation of fats in the blood leaking into arterial walls. More recently, the main fats concerned have been shown to comprise low density lipoproteins, which contain cholesterol, and accumulate in the vessel wall in oxidised and related modified forms (oxLDL). These abnormal forms are highly inflammatory, activating white blood cells called macrophages. It is thought that OxLDL 'fools' macrophages into behaving as if pathogens were present and causing further vessel wall damage. The endothelium is now viewed as a major player in atherogenesis, particularly for connecting atherosclerotic risk factors to vessel wall leakiness and leukocyte recruitment. This view is the 'endothelial response to injury' theory propounded by Ross in 1972 and 1982.
Vasculitis is an inflammation of the blood vessels. In most forms, it is accompanied by destruction of the vessel wall, often seen as fibrinoid necrosis. These necroses come in multiple forms, each associated with a specific type of autoantibody. Anti-endothelial antibodies are associated with Takayasu's arteritis and anti-neutrophil cytoplasmic antibodies with macroscopic and microscipic polyarteritis nodosa or with Churg-Strauss syndrome.