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 Yuan

Research output: Contribution to journalArticle

315 Citations (Scopus)

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

Fingerprint

Transient Receptor Potential Channels
Pulmonary Artery
Smooth Muscle Myocytes
Cell Proliferation
Lung
Hypertrophy
Blood Vessels
Familial Primary Pulmonary Hypertension
Mitosis
Pulmonary Hypertension
Vascular Resistance
Small Interfering RNA
Cell Cycle
Protein Isoforms
Proteins
Messenger RNA

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension. / Yu, Ying; Fantozzi, Ivana; Remillard, Carmelle V.; Landsberg, Judd W.; Kunichika, Naomi; Platoshyn, Oleksandr; Tigno, Donna D.; Thistlethwaite, Patricia A.; Rubin, Lewis J.; Yuan, Jason.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 38, 21.09.2004, p. 13861-13866.

Research output: Contribution to journalArticle

Yu, Y, Fantozzi, I, Remillard, CV, Landsberg, JW, Kunichika, N, Platoshyn, O, Tigno, DD, Thistlethwaite, PA, Rubin, LJ & Yuan, 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, vol. 101, no. 38, pp. 13861-13866. https://doi.org/10.1073/pnas.0405908101
Yu, Ying ; Fantozzi, Ivana ; Remillard, Carmelle V. ; Landsberg, Judd W. ; Kunichika, Naomi ; Platoshyn, Oleksandr ; Tigno, Donna D. ; Thistlethwaite, Patricia A. ; Rubin, Lewis J. ; Yuan, Jason. / Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 38. pp. 13861-13866.
@article{d71e08d9bd804a40828262d2d0cc2ead,
title = "Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension",
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.",
author = "Ying Yu and Ivana Fantozzi and Remillard, {Carmelle V.} and Landsberg, {Judd W.} and Naomi Kunichika and Oleksandr Platoshyn and Tigno, {Donna D.} and Thistlethwaite, {Patricia A.} and Rubin, {Lewis J.} and Jason Yuan",
year = "2004",
month = "9",
day = "21",
doi = "10.1073/pnas.0405908101",
language = "English (US)",
volume = "101",
pages = "13861--13866",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "38",

}

TY - JOUR

T1 - Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension

AU - Yu, Ying

AU - Fantozzi, Ivana

AU - Remillard, Carmelle V.

AU - Landsberg, Judd W.

AU - Kunichika, Naomi

AU - Platoshyn, Oleksandr

AU - Tigno, Donna D.

AU - Thistlethwaite, Patricia A.

AU - Rubin, Lewis J.

AU - Yuan, Jason

PY - 2004/9/21

Y1 - 2004/9/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=4644290321&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4644290321&partnerID=8YFLogxK

U2 - 10.1073/pnas.0405908101

DO - 10.1073/pnas.0405908101

M3 - Article

C2 - 15358862

AN - SCOPUS:4644290321

VL - 101

SP - 13861

EP - 13866

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 38

ER -