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

Ying Yu, Ivana Fantozzi, Carmelle V. Remillard, Judd W. Landsberg, Naomi Kunichika, Oleksandr Platoshyn, Donna D. Tigno, Patricia A. Thistlethwaite, Lewis J. Rubin, Jason X.J. Yuan

Research output: Contribution to journalArticle

321 Scopus citations

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 Ca2+ influx is an important stimulus for PASMC proliferation. Transient receptor potential (TRP) channel genes encode Ca2+ channels that are responsible for Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)13861-13866
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number38
DOIs
StatePublished - Sep 21 2004
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension'. Together they form a unique fingerprint.

  • Cite this

    Yu, Y., Fantozzi, I., Remillard, C. V., Landsberg, J. W., Kunichika, N., Platoshyn, O., Tigno, D. D., Thistlethwaite, P. A., Rubin, L. J., & Yuan, J. X. J. (2004). 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, 101(38), 13861-13866. https://doi.org/10.1073/pnas.0405908101