HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/1/L202    most recent 00064.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Chattergoon, N. N. Articles by Jeter, J. R. Search for Related Content PubMed PubMed Citation Articles by Chattergoon, N. N. Articles by Jeter, J. R., Jr.

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

Departments of ¹Pharmacology and ²Structural and Cellular Biology, Tulane Medical School, New Orleans, Louisiana

Submitted 26 February 2004 ; accepted in final form 15 July 2004

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 CGRP. 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.

vascular smooth muscle cells; nitric oxide; adenovirus

This article has been cited by other articles:

				B. Li, L. Yang, J. Shen, C. Wang, and Z. Jiang The Antiproliferative Effect of Sildenafil on Pulmonary Artery Smooth Muscle Cells Is Mediated via Upregulation of Mitogen-Activated Protein Kinase Phosphatase-1 and Degradation of Extracellular Signal-Regulated Kinase 1/2 Phosphorylation Anesth. Analg., October 1, 2007; 105(4): 1034 - 1041. [Abstract] [Full Text] [PDF]

				N N Chattergoon, G D Giraud, and K L Thornburg Thyroid hormone inhibits proliferation of fetal cardiac myocytes in vitro J. Endocrinol., February 1, 2007; 192(2): R1 - R8. [Abstract] [Full Text] [PDF]