Antiproliferative effects of calcitonin gene-related peptide in aortic and pulmonary artery smooth muscle cells

N. N. Chattergoon, F. M. D'Souza, W. Deng, H. Chen, A. L. Hyman, P. J. Kadowitz, J. R. Jeter

    Research output: Contribution to journalArticle

    43 Scopus citations

    Abstract

    Pulmonary hypertension is characterized by vascular remodeling involving smooth muscle cell proliferation and migration. Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are potent vasodilators, and the inhibition of aortic smooth muscle cell (ASMC) proliferation by NO has been documented, but less is known about the effects of CGRP. The mechanism by which overexpression of CGRP inhibits proliferation in pulmonary artery smooth muscle cells (PASMC) and ASMC following in vitro transfection by the gene coding for prepro-CGRP was investigated. Increased expression of p53 is known to stimulate p21, which inhibits G1 cyclin/cdk complexes, thereby inhibiting cell proliferation. We hypothesize that p53 and p21 are involved in the growth inhibitory effect of CGRP. In this study, CGRP was shown to inhibit ASMC and PASMC proliferation. In PASMC transfected with CGRP and exposed to a PKA inhibitor (PKAi), cell proliferation was restored. p53 and p21 expression increased in CGRP-treated cells but decreased in cells treated with CGRP and PKAi. PASMC treated with CGRP and a PKG inhibitor (PKGi) recovered from inhibition of proliferation induced by CORP. ASMC treated with CGRP and then PKAi or PKGi recovered only when exposed to the PKAi and not PKGi. Although CGRP is thought to act through a cAMP-dependent pathway, cGMP involvement in the response to CGRP has been reported. It is concluded that p53 plays a role in CGRP-induced inhibition of cell proliferation and cAMP/PKA appears to mediate this effect in ASMC and PASMC, whereas cGMP appears to be involved in PASMC proliferation.

    Original languageEnglish (US)
    Pages (from-to)L202-L211
    JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
    Volume288
    Issue number1 32-1
    DOIs
    StatePublished - Jan 1 2005

      Fingerprint

    Keywords

    • Adenovirus
    • Nitric oxide
    • Vascular smooth muscle cells

    ASJC Scopus subject areas

    • Physiology
    • Pulmonary and Respiratory Medicine
    • Physiology (medical)
    • Cell Biology

    Cite this