• arteriosclerosis: common name for three diseases which all result in thickened, inelastic vessel walls
• atherosclerosis: occurs in large and medium arteries; intima and inner media are involved
• Monkeberg's medial sclerosis: calcifications in the media of large and medium arteries
• can lead to the development of atherosclerosis
• arteriolar sclerosis: results in thickening and narrowing of arterioles

• intima: endothelium functions as a barrier; dysfunction allows LDL and other materials to enter the intima
• separated from the media by internal elastic membrane; O₂ supply is via diffusion
• media: reticulated arrangement of smooth muscle cells and fibroblasts; may contain elastic fibers, vaso vasorum
• adventitia: fibroblasts, collagen, blood vessels

Etiology: the main hypothesis is response to injury – inflammatory type lesion

• endothelial injury: allows accumulation of lipids in the intima, also promotes inflammatory response
• the two proposed mechanisms are (1) injury due to normal hemodynamics, and (2) hypercholesterolemia
• also proposed that agents such as herpes virus and chlamydia may induce atherosclerosis
• lipid accumulation: leads to increased free radical production Þ oxidized LDL
• oxidized LDL is readily taken up by macrophages, is chemotactic to monocytes; inhibits macrophage mobility
• once they are a part of the plaque; it is also cytotoxic and immunogenic
• macrophages: take up lipids and debris contributing to the size of the lesion; also produce factors such as IL-1 and TNF which recruit other leukocytes including T-cells and promote inflammation and more damage Þ cyclic response
• smooth muscle cells: fibroblast and smooth muscle proliferation leads to ECM deposits in the intima which converts the fatty streaks into mature fibroatheromas
• Note: endothelial injury is the key in the current hypothesis. It used to be thought that there had to be disruption of the endothelium, but this has been found to be untrue; atherosclerosis is promoted by a dysfunctional endothelium, it may or may not have been disrupted by the injury

• fatty streaks and dots: isolated foamy macrophages and intracellular lipid accumulation; microhemorrhages
• seen in large and medium elastic arteries as young as 1 yo
• may or may not progress to atherosclerosis
• intermediate lesions: small extracellular lipid pools begin to develop
• atheroma: a core of extracellular lipid has formed
• advanced lesion (fibroatheroma): white fibrous plaque sits over the atheroma; firm; may contain organized thrombi
• the fibrous cap is generally thick and stable Þ few acute problems occur (leads to slow obstruction)
• complicated lesion: fibrous cap is unstable; ulceration, hemorrhage, thrombosis is very likely to lead to acute problems

• brain: syncope, stroke, hemorrhage
• kidney: HTN Þ feeds back to promote more atherosclerosis
• aorta and other arteries: weakened walls can lead to aneurysm (75% mortality)
• heart: ischemia Þ angina, fibrosis, MI (50% of MI present at autopsy without prior history)
• weakened walls Þ dilation and rupture
• coronary artery lumen narrowing Þ ischemia

• teens: fatty streaks begin to develop
• 40s: calcification and conversion to complex plaques occurs
• 50s - 60s: MI, AAA, CVA