Aging and arteriosclerosis. I. Development of myointimal hyperplasia after endothelial injury.

Abstract

Old Fischer 344 rats are more susceptible to vascular lesions after arterial endothelial injury than are young animals. Thus, 20-26-mo-old Fischer 344 rats developed greater and more persistent intimal proliferative lesions than did 2-5-mo-old rats after aortic endothelial denudation. 3 d after deendothelialization, intimal thickness was increased two-fold in both old and young animals. However, 14 d after endothelial injury, intimal thickness had increased nearly five times in old animals, but had regressed to normal in young animals. Intimal thickness of young aortic grafts transplanted into young recipients did not differ significantly from adjacent host aorta or autotransplanted aortic segments 6 wk after surgery. In contrast, intimal thickness of old grafts transplanted into young recipients was eight times greater than adjacent young host aorta 6 wk after surgery. The density of cell nuclei in the intima of old grafts was also much greater than that in young grafts. Thus, in two experimental models of vascular injury, old rats have consistently had greater myointimal hyperplasia than young rats. The increased proliferative response of aortic smooth muscle cells after vascular injury of old animals may contribute to the increased prevalence of vascular disease with age.

Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises

“…10 Atherosclerotic plaques and inflammatory cells, however, are conspicuous in their absence. Neointimal growth in response to injury is markedly enhanced in older versus younger rats 11,12 and is due to factors intrinsic to the vessel wall, because the excessive intimal hyperplasia is still observed when aortae from old animals are transplanted into younger ones. 12 After balloon injury to the rat carotid artery, medial SMCs are activated and they begin to proliferate, and subsequently migrate to the intimal layer, invading the complex extracellular matrix of the vessel wall through discontinuities in the internal elastic lamina.…”

“…Neointimal growth in response to injury is markedly enhanced in older versus younger rats 11,12 and is due to factors intrinsic to the vessel wall, because the excessive intimal hyperplasia is still observed when aortae from old animals are transplanted into younger ones. 12 After balloon injury to the rat carotid artery, medial SMCs are activated and they begin to proliferate, and subsequently migrate to the intimal layer, invading the complex extracellular matrix of the vessel wall through discontinuities in the internal elastic lamina. In addition to the migration of medial SMCs, recent evidence suggests that hematopoietic stem cells that originate in the bone marrow also contribute to the neointimal proliferation after arterial injury by migrating into the subendothelial layer from the lumenal side of the vascular wall and differentiating into vascular SMC.…”

“…It is also noteworthy that early passage aortic vascular SMCs of old rats exhibit an exaggerated chemotactic response to platelet-derived growth factor (PDGF), whereas cells from young aortae require several additional passages in culture to generate an equivalent response ( Figure 1D). Thus, the exaggerated response of old vessels to experimental injury in vivo 11,12 may be attributable, in part, to enhanced SMC chemotaxis or proliferation in response to growth factors such as PDGF. 16,17 Excessive neointimal formation observed after balloon injury to the rat carotid artery can be prevented by cleaving the mRNA of the early growth response gene, Egr-1, a zinc-finger transcription factor that modulates a host of stress-responsive genes, including PDGF and TGF-␤, which impact cellular proliferation, migration, and apoptosis.…”

Rat Aortic MCP-1 and Its Receptor CCR2 Increase With Age and Alter Vascular Smooth Muscle Cell Function

“…[17][18][19][20] Structural and biochemical changes that occur within large arteries with aging are accompanied by a shift of the VSMC phenotype from the "contractile" to the "synthetic" state, characterized by an increased proliferative and migratory responsiveness to growth factors. [21][22][23] The discrepancies in the literature about VSMC proliferation are possibly due to species specificity and the factors used experimentally to stimulate proliferation. Migration and proliferation of VSMCs, endothelial cells, or macrophages are also mediated by chemokines.…”

Histopathologic changes of the radial artery wall secondary to transradial catheterization

“…14 In an experimental model of arterial injury, intimal thickness as early as three days after endothelial denudation was twice that of uninjured aorta. 15 In our study, there was significantly more intimal hyperplasia at the end of the artery injured by the introducer sheath when compared to arteries that were never injured. The same findings were observed when the distal ends of the arteries were compared with the more proximal ends, supporting the concept that endothelial denudation is the major trigger of the process.…”