Limited effects of hyperlipidemia on the arterial smooth muscle response to mechanical stress

Arteries respond to long-term changes in flow rate by alterations in caliber that tend to restore wall shear stress to normal baseline levels. Changes in radius, pressure, or geometric configuration elicit changes in structure and composition of the media in keeping with the altered level and distribution of tensile stresses. Similar stabilizing adaptations occur in the presence of conditions that induce the formation of atherosclerotic plaques, but the ultimate effectiveness of these reactions is variable. Several recent experiments provide information on the possible effects of hyperlipidemia on the smooth muscle cell (SMC) response to normal or increased levels of mechanical stress: (a) Normolipemic serum increases collagen synthesis by SMCs grown on purified elastin membranes compared to synthesis in serum-free medium, but synthesis is not further enhanced by cyclic stretching of the cells. Collagen production increase is less marked in hyperlipemic serum, but cyclic stretching raises synthesis to a degree comparable to that noted for serum-free medium, (b) The increase in artery diameter in response to increased flow rate and the elaboration of media components in relation to the increase in diameter are not hampered by hyperlipidemia. (c) The compensatory enlargement of arteries in response to plaque formation is not prevented by hyperlipidemia even in the presence of hypertension, (d) The healing of a transmural necrotizing injury of the media is, however, retarded and incomplete in the presence of hyperlipidemia. These findings indicate that hyperlipidemia per se does not necessarily interfere with the SMC response to mechanical stimuli. The usual adaptive reactions remain intact. Conditions that interfere with the transmission to the SMCs of the mechanical stimuli, limit adjustments in caliber by means of physical constraints, or interfere with the access to SMCs of the necessary trophic metabolites may prevent an adequate response. Individual differences may also be attributable to suppression of SMC function by metabolic deficiencies or by other risk factors that potentiate vascular disease.