Atherosclerosis resistance in rats correlates with lack of expansion of an immature smooth muscle cell population.
In this study we asked whether the well-known atherosclerosis resistance of rats might be reduced with aging. Two groups of young, adult and aged Wistar rats, one of which was kept on a standard, low-cholesterol (CT) diet, and the other one was fed a 2% CT diet for 2 months were enrolled. Potential modifications in the phenotypic profile of aortic smooth muscle (SM) were assessed by SDS-gel electrophoresis, Western blotting and immunofluorescence procedures using a panel of monoclonal antibodies to myosin isoforms, cytoskeletal and extracellular matrix proteins. With development and aging, the expression of 196-kD non-muscle-type myosin heavy-chain isoform (MyHC), the EIIIA fibronectin variant and keratins was downregulated, whereas that of the 204- and 200-kD SM-type MyHC isoforms, SM-type alpha-actin and desmin did not change. The levels of hypercholesterolemia achieved in this model did not substantially modify the distribution of the downregulated markers, except for the subendothelial grouping of immature SM cells in aged rats. Morphometric measurements indicated a slight increase of medial cross-sectional area accompanied by a decrease in total SM cell number, both with aging and with hypercholesterolemia. In no circumstance was the presence of atherosclerotic lesions histologically detectable. Bromo-deoxyuridine (BrdU) incorporation analysis revealed a marked age-dependent decline in DNA synthesis and the formation of binucleated cells in aged aortas. This pattern was not influenced by hypercholesterolemia, except in aged rats where BrdU-positive SM cells are almost doubled. Our data indicate that aging and hypercholesterolemia cannot affect the phenotypic stability of rat SM cells and confirm that the change from a fully differentiated to an immature state is a general prerequisite to allow the development of atherosclerotic lesions in mammalian species.
Amore
B
B
Department of Biomedical Sciences, University of Padova, Italy.
Chiavegato
A
A
Paulon
T
T
Pauletto
P
P
Sartore
S
S
D000367:Age Factors; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology; D002455:Cell Division; D002791:Cholesterol, Dietary / Q000378:metabolism*; D003893:Desmin / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D007633:Keratins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D009218:Myosins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014746:Vimentin / Q000378:metabolism
D002791:Cholesterol, Dietary; D003893:Desmin; D014746:Vimentin; D007633:Keratins; D009218:Myosins