Pharmacological role of HB-EGF shedding by angiotensin II in cardiomyocytes

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Updated: Aug 11, 2026

Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
09:16

Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes

Published on: June 3, 2018

Seiji Takashima1

  • 1Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. takasima@medone.med.osaka-u.ac.jp

Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
|July 28, 2004
PubMed

Insights

Angiotensin II (AGII) triggers cardiac hypertrophy via a novel pathway involving HB-EGF. This discovery sheds light on heart failure mechanisms and potential therapeutic targets.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Pharmacology

Background:

  • Angiotensin II (AGII) is a known inducer of cardiac hypertrophy, a condition linked to reduced cardiac function and heart failure.
  • AGII antagonists show protective effects, suggesting AGII's role in the progression from hypertrophy to heart failure.

Purpose of the Study:

  • To elucidate a novel mechanism of AGII-induced cardiac hypertrophy mediated by HB-EGF.
  • To investigate the role of EGF receptor transactivation in AGII's effects on cardiomyocytes.

Main Methods:

  • Utilized cultured cardiomyocytes to study AGII's effects.
  • Employed a metalloproteinase inhibitor (KBR-7785) and an HB-EGF-neutralizing antibody (#19) to block specific pathways.
  • Assessed cardiac hypertrophy in vitro and in vivo.

Main Results:

  • AGII induced transactivation of the EGF receptor in cardiomyocytes.
  • Metalloproteinase inhibition and HB-EGF neutralization blocked AGII-induced EGF receptor transactivation.
  • Both interventions attenuated cardiac hypertrophy caused by AGII, in vitro and in vivo.

Conclusions:

  • AGII activates metalloproteinases, leading to the shedding of HB-EGF.
  • Released HB-EGF binds to the EGF receptor, mediating AGII-induced cardiac hypertrophy.
  • This HB-EGF-mediated EGF receptor transactivation may represent a general mechanism for AGII's pharmacological actions.

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