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PMID: 15358862 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 38 ·2004-09-21 ·Pages 13861-6

Yu Y, Fantozzi I, Remillard CV, Landsberg JW, Kunichika N, Platoshyn O, Tigno DD, Thistlethwaite PA, Rubin LJ, Yuan JX

Abstract

Pulmonary vascular medial hypertrophy caused by excessive pulmonary artery smooth muscle cell (PASMC) proliferation is a major cause for the elevated pulmonary vascular resistance in patients with idiopathic pulmonary arterial hypertension (IPAH). Increased Ca(2+) influx is an important stimulus for PASMC proliferation. Transient receptor potential (TRP) channel genes encode Ca(2+) channels that are responsible for Ca(2+) entry during cell proliferation. Normal human PASMC expressed multiple canonical TRP (TRPC) isoforms; TRPC6 was highly expressed and TRPC3 was minimally expressed. The protein expression of TRPC6 in normal PASMC closely correlated with the expression of Ki67, suggesting that TRPC6 expression is involved in the transition of PASMC from quiescent phase to mitosis. In lung tissues and PASMC from IPAH patients, the mRNA and protein expression of TRPC3 and -6 were much higher than in those from normotensive or secondary pulmonary hypertension patients. Inhibition of TRPC6 expression with TRPC6 small interfering RNA markedly attenuated IPAH-PASMC proliferation. These results demonstrate that expression of TRPC channels correlates with the progression of the cell cycle in PASMC. TRPC channel overexpression may be partially responsible for the increased PASMC proliferation and pulmonary vascular medial hypertrophy in IPAH patients.

MeSH Terms
Adult Aged Blood Pressure Calcium Channels/genetics Cell Cycle Cell Division DNA Replication Female Gene Expression Regulation Humans Hypertension, Pulmonary/genetics,pathology,physiopathology Ion Channels/genetics Lung Transplantation Male Middle Aged Mitosis Pulmonary Artery/pathology Reverse Transcriptase Polymerase Chain Reaction TRPC Cation Channels TRPC6 Cation Channel Vascular Resistance/physiology
Chemicals
Calcium Channels Ion Channels TRPC Cation Channels TRPC3 cation channel TRPC4 ion channel TRPC6 Cation Channel TRPC6 protein, human
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Yu Ying
Department of Medicine, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Fantozzi Ivana
Remillard Carmelle V
Landsberg Judd W
Kunichika Naomi
Platoshyn Oleksandr
Tigno Donna D
Thistlethwaite Patricia A
Rubin Lewis J
Yuan Jason X-J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0405908101
Published
2004-09-21
Epub
2004-00-09
Pages
13861-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC518765
Subset
IM
Grants
NHLBI NIH HHS · R29 HL054043 · United States
NHLBI NIH HHS · U01 HL069758 · United States
NHLBI NIH HHS · R01 HL054043 · United States
NHLBI NIH HHS · P01 HL066941 · United States
NHLBI NIH HHS · R01 HL064945 · United States
NHLBI NIH HHS · R01 HL066012 · United States
External Links
PubMed source DOI: 10.1073/pnas.0405908101 PMC Full Text View journal details
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