Calcineurin plays a critical role in the development of pressure overload-induced cardiac hypertrophy

Yunzeng Zou, Yukio Hiroi, Hiroki Uozumi, Eiki Takimoto, Haruhiro Toko, Weidong Zhu, Sumiyo Kudoh, Miho Mizukami, Masaki Shimoyama, Futoshi Shibasaki, Ryozo Nagai, Yoshio Yazaki, Issei Komuro

Research output: Contribution to journalArticle

Abstract

Background - Although activation of the Ca2+-dependent phosphatase calcineurin has been reported to induce cardio-myocyte hypertrophy, whether calcineurin is involved in pressure overload-induced cardiac hypertrophy remains controversial. Methods and Results - We examined in the present study the role of calcineurin in pressure overload-induced cardiac hypertrophy using transgenic mice that overexpress the dominant negative mutant of calcineurin specifically in the heart. There were no significant differences in body weight, blood pressure, heart rate, heart weight, and the cardiac calcineurin activity between the transgenic mice and their littermate wild-type mice at basal state. The activity of calcineurin was markedly increased by pressure overload produced by constriction of the abdominal aorta in the heart of wild-type mice but less increased in the heart of the transgenic mice. Pressure overload induced increases in heart weight, wall thickness of the left ventricle, and diameter of cardiomyocytes; reprogramming of expressions of immediate early response genes and fetal-type genes; activation of extracellular signal-regulated protein kinases; and fibrosis. All these hypertrophic responses were more prominent in the wild-type mice than in the transgenic mice. Conclusions - These results suggest that calcineurin plays a critical role in the development of pressure overload-induced cardiac hypertrophy.

Original languageEnglish (US)
Pages (from-to)97-101
Number of pages5
JournalCirculation
Volume104
Issue number1
Publication statusPublished - Jul 3 2001
Externally publishedYes

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Keywords

  • Calcineurin
  • Genes
  • Hypertrophy
  • Pressure

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Zou, Y., Hiroi, Y., Uozumi, H., Takimoto, E., Toko, H., Zhu, W., ... Komuro, I. (2001). Calcineurin plays a critical role in the development of pressure overload-induced cardiac hypertrophy. Circulation, 104(1), 97-101.