Role of Gαq in smooth muscle cell proliferation

Background: G protein-linked receptors are involved in the processes that lead to intimal hyperplasia. This study examined the role of Gαq signaling pathways in vascular smooth muscle cell (SMC) proliferation in vitro. Methods: Rat pulmonary artery SMCs were cultured in vitro. Standard assays of cellular DNA synthesis, proliferation, phospholipase C-β (PLCβ) activation, and extracellular signal-regulated kinase (ERK1/2) phosphorylation were used to study the response to angiotensin II (a specific Gαq agonist; 0.1-100 μmol/L) in the presence and absence of GP-2A (a competitive Gαq inhibitor; 10 μmol/L) and the PLCβ inhibitor U73122 (10 μmol/L). Results: Angiotensin II induced SMC DNA synthesis and cell proliferation. DNA synthesis was inhibited by both Gαq inhibitor, GP-2A, and PLCβ inhibitor U73122, in a dose-dependent manner (66% ± 7% of angiotensin II alone at 10 μmol/L for GP-2A [P < .05] and 63% ± 6% for U73122). GP-2A completely inhibited angiotensin II-induced Gaq-mediated PLCβ phosphorylation. Activation of ERK1/2 by angiotensin II was significantly reduced by GP-2A (P < .05) and by PLCβ inhibition (P < .05). Conclusion: Inhibition of Gαq decreases PLCβ and ERK1/2 phosphorylation, leading to decreased SMC proliferation in vitro. Understanding specific signal transduction pathways will be an integral component of anti-restenosis therapy.