FIGURE 1. Initiation and progression of atherosclerosis.

From the following article:

Translating molecular discoveries into new therapies for atherosclerosis

Daniel J. Rader & Alan Daugherty

Nature 451, 904-913(21 February 2008)

doi:10.1038/nature06796

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Atherosclerosis occurs at sites in the arterial tree where laminar flow is disrupted. A lesion begins as a fatty streak (a) and can develop into an intermediate lesion (b), and then into a lesion that is vulnerable to rupture (c) and, finally, into an advanced obstructive lesion (d). A more detailed description of this process follows. a, Atherogenic lipoproteins such as low-density lipoproteins (LDLs) enter the intima, where they are modified by oxidation or enzymatic activity and aggregate within the extracellular intimal space, thereby increasing their phagocytosis by macrophages. Unregulated uptake of atherogenic lipoproteins by macrophages leads to the generation of foam cells, which are laden with lipid. The accumulation of foam cells leads to the formation of fatty streaks, which are often present in the aorta of children, the coronary arteries of adolescents, and other peripheral vessels of young adults. Although they cause no clinical pathology, fatty streaks are widely considered to be the initial lesion leading to the development of complex atherosclerotic lesions. b, Vascular smooth muscle cells — either recruited from the media into the intima or proliferating within the intima — contribute to this process by secreting large amounts of extracellular-matrix components, such as collagen. The presence of these increases the retention and aggregation of atherogenic lipoproteins. In addition to monocytes, other types of leukocyte, particularly T cells, are recruited to atherosclerotic lesions and help to perpetuate a state of chronic inflammation. As the plaque grows, compensatory remodelling takes place, such that the size of the lumen is preserved while its overall diameter increases. c, Foam cells eventually die, resulting in the release of cellular debris and crystalline cholesterol. In addition, smooth muscle cells form a fibrous cap beneath the endothelium, and this walls off the plaque from the blood. This process contributes to the formation of a necrotic core within the plaque and further promotes the recruitment of inflammatory cells. This non-obstructive plaque can rupture or the endothelium can erode, resulting in the exposure of thrombogenic material, including tissue factor, and the formation of a thrombus in the lumen. If the thrombus is large enough, it blocks the artery, which causes an acute coronary syndrome or myocardial infarction (heart attack). d, Ultimately, if the plaque does not rupture and the lesion continues to grow, the lesion can encroach on the lumen and result in clinically obstructive disease.

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