Effect of angiotensin II on human vascular smooth muscle cell growth.
Inhibitors of the production of endogenous angiotensin II (A-II) can diminish the hyperplastic response produced by arterial injury in animals; however, a similar effect in humans has not been observed. To explain this discrepancy, we compared the effect of A-II on rat aortic smooth muscle cells (R-SMC) and smooth muscle cells derived from human saphenous veins (H-SMC). A-II (10-1000 nM) significantly increased the proliferative rate of R-SMC incubated in 10% serum, but a similar effect was not observed with H-SMC. Incubation of R-SMC for 24 hr with A-II (1 microM) produced a significant increase in cell size (7%) and protein production (18%), whereas no hypertrophic response was noted in H-SMC exposed to A-II. In neither R-SMC nor H-SMC did A-II, in any concentration, induce cell migration. Stimulation of R-SMC with A-II resulted in tyrosine phosphorylation of five proteins (approximately 120, approximately 108, approximately 68, 45, 42 kDa). The 42- and 45-kDa proteins, which we have previously identified as mitogen-activated protein kinases (MAP-K), remained phosphorylated for 1 hr. In H-SMC, only MAP kinases were tyrosine phosphorylated, but with less intensity than in R-SMC, and only for 20 min. In protein kinase C-depleted SMC, tyrosine phosphorylation of MAP kinase was inhibited in both cell types. A-II produced hypertrophy and hyperplasia of R-SMC, but not H-SMC. Differences in intracellular signaling might account for these disparate effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Mii
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Department of Surgery, Beth Israel Hospital, Boston, Massachusetts 02215.
Ware
J A
JA
Mallette
S A
SA
Kent
K C
KC
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D006984:Hypertrophy; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014443:Tyrosine / Q000378:metabolism
D000804:Angiotensin II; D014443:Tyrosine; D017871:Calcium-Calmodulin-Dependent Protein Kinases