IntimalThickening:AStereotypicalResponsetoVascularInjury
Vascular injury leading to EC loss or dysfunction stimulates SMC growth, ECM synthesis, and thickening of the vascular wall. Healing of injured vessels involves the migration of SMCs or SMC precursor cells into the intima. These cells then proliferate and synthesize ECM in much the same way that fibroblasts fill in a wound elsewhere in the body (
Fig. 10.6), forming a neointima that typically is covered by an intact EC layer. This neointimal response occurs with any form of vascular damage or dysfunction, including infection, inflammation, immune injury, physical trauma (e.g., from a balloon catheter or hypertension), or toxic exposure (e.g. oxidized lipids or cigarette smoke). Thus, intimal thickening is a stereotypical response of the vessel wall to any insult.
Of note, the phenotype of neointimal SMCs is distinct from medial SMCs. Thus, neointimal SMCs are not contractile like medial SMCs, but do have the capacity to divide and have a considerably greater synthetic capacity http://ebooksmedicine.net 1. Recruitment of smooth muscle 2. Smooth muscle 3. Elaboration of cells or smooth muscle precursor cell mitosis extracellular matrix
Endothelium cells to the intima
Fig. 10.6 Stereotypicalresponsetovascularinjury.Schematicdiagramofintimalthickening,emphasizingintimalsmoothmusclecellmigrationandprolifera-tionassociatedwithextracellularmatrixsynthesis.Intimalsmoothmusclecellsmayderivefromtheunderlyingmediaormayberecruitedfromcirculatingprecursors;theyaredepictedinacolordifferentfromthatofthemedialsmoothmusclecells,toemphasizetheirdistinctphenotype.
than their sleepy colleagues in the media. Although neointimal cells were previously thought to arise exclusively from dedifferentiated medial SMCs, at least a subset is derived from circulating precursor cells. The migratory, proliferative, and synthetic activities of the intimal SMCs are regulated by growth factors and cytokines produced by platelets, ECs, and macrophages, as well as by activated coagulation and complement factors (as discussed earlier).
With restoration and/or normalization of the EC layer, intimal SMCs can return to a nonproliferative state, but not before the healing response has produced intimal thickening. With persistent or recurrent insults, further thickening can occur that leads to the stenosis of smalland medium-sized blood vessels (e.g., as in atherosclerosis, discussed later). As a final note, it is also important to recognize that gradual ongoing intimal thickening appears to be a part of “normal aging.” Fortunately, such age-related intimal change typically is of no consequence, in part because compensatory outward remodeling of the vessel wall results in little net change in the luminal diameter.
Arteriosclerosis literally means “hardening of the arteries”; it is a generic term reflecting arterial wall thickening and loss of elasticity. Four distinct types are recognized, each with different clinical and pathologic causes and consequences:
Arteriolosclerosis affects small arteries and arterioles and may cause downstream ischemic injury. The two variants, hyaline and hyperplastic arteriolosclerosis, were discussed earlier in relation to hypertension.
Mönckeberg medial sclerosis is characterized by the presence of calcific deposits in muscular arteries, usually centered on the internal elastic lamina, and typically in individuals older than 50 years of age. The lesions do not encroach on the vessel lumen and usually are not clinically significant.