Phenotypic heterogeneity influences the behavior of rat aortic smooth muscle cells in collagen lattice.
Phenotypic modulation of vascular smooth muscle cells (SMCs) in atherosclerosis and restenosis involves responses to the surrounding microenvironment. SMCs obtained by enzymatic digestion from tunica media of newborn, young adult (YA) and old rats and from the thickened intima (TI) and underlying media of young adult rat aortas 15 days after ballooning were entrapped in floating populated collagen lattice (PCL). TI-SMCs elongated but were poor at PCL contraction and remodeling and expressed less alpha2 integrin compared to other SMCs that appeared more dendritic. During early phases of PCL contraction, SMCs showed a marked decrease in the expression of alpha-smooth muscle actin and myosin. SMCs other than TI-SMCs required 7 days to re-express alpha-smooth muscle actin and myosin. Only TI-SMCs in PCL were able to divide in 48 h, with a greater proportion in S and G2-M cell cycle phases compared to other SMCs. Anti-alpha2 integrin antibody markedly inhibited contraction but not proliferation in YA-SMC-PLCs; anti-alpha1 and anti-alpha2 integrin antibodies induced a similar slight inhibition in TI-SMC-PCLs. Finally, TI-SMCs rapidly migrated from PCL on plastic reacquiring their epithelioid phenotype. Heterogeneity in proliferation and cytoskeleton as well the capacity to remodel the extracellular matrix are maintained, when SMCs are suspended in PCLs.
Orlandi
Augusto
A
Anatomic Pathology, Dept. of Biopathology and Image Diagnostics, Tor Vergata University of Rome, Via Montpellier 1, 00133 Rome, Italy. orlandi@uniroma2.it
Ferlosio
Amedeo
A
Gabbiani
Giulio
G
Spagnoli
Luigi Giusto
LG
Ehrlich
Paul H
PH
D000199:Actins / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001011:Aorta / Q000166:cytology*; D002453:Cell Cycle; D049109:Cell Proliferation; D003094:Collagen / Q000737:chemistry; D039423:Integrin alpha1 / Q000187:drug effects / Q000378:metabolism; D039421:Integrin alpha2 / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure*; D032389:Myocytes, Smooth Muscle / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure*; D010641:Phenotype; D051381:Rats; D024745:Smooth Muscle Myosins / Q000378:metabolism; D017539:Tunica Intima / Q000166:cytology
D000199:Actins; D000906:Antibodies; D003094:Collagen; D039423:Integrin alpha1; D039421:Integrin alpha2; D024745:Smooth Muscle Myosins; C498862:Acta2 protein, rat