Aging, smooth muscle cells and vascular pathobiology: implications for atherosclerosis.
Epidemiological and autopsy studies suggest a close link between aging and the clinical manifestation of atherosclerosis. Several experiments show increased arterial susceptibility to atherogenetic stimuli in aged subjects. All together, these findings support the concept that aging represents an independent atherogenetic risk factor, intimately associated to other parietal, microenvironmental and systemic noxae. Smooth muscle cells (SMCs) represent the major arterial cell population. As aging occurs, SMCs progressively migrate from the tunica media and accumulate into the tunica intima. Myointimal thickening may represent the site where low-grade atherogenic stimuli cause early development and more severe lesion progression. Intimal SMC accumulation is characterized from a switch, from a differentiated to a synthetic phenotype, with reduced myocytic cytoskeletal markers and the expression of new proteins. Aging also associates to changes of SMC proliferative and apoptotic behavior and response to growth factors, such as transforming growth factor-beta1. The alteration of SMC properties represents a crucial event in the pathobiology of arterial wall, since it contributes to the vascular remodeling and decline of function with aging and favors the progression of atherosclerosis. Increased knowledge of biomolecular mechanisms regulating these events helps to develop new strategies aimed at contrasting the adverse effect of vascular aging.
Orlandi
Augusto
A
Anatomic Pathology Institute, Department of Biopathology, Tor Vergata University of Rome, Via Montpellier 1, Rome, Italy. orlandi@uniroma2.it
Bochaton-Piallat
Marie-Luce
ML
Gabbiani
Giulio
G
Spagnoli
Luigi Giusto
LG
D000375:Aging / Q000473:pathology* / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology; D050197:Atherosclerosis / Q000473:pathology* / Q000503:physiopathology*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000502:physiology; D012307:Risk Factors; D017539:Tunica Intima / Q000473:pathology*