Low-intensity pulsed ultrasound enhances angiogenesis and ameliorates left ventricular dysfunction in a mouse model of acute myocardial infarction

Tomohiko Shindo, Kenta Ito, Tsuyoshi Ogata, Kazuaki Hatanaka, Ryo Kurosawa, Kumiko Eguchi, Yuta Kagaya, Kenichiro Hanawa, Kentaro Aizawa, Takashi Shiroto, Sachie Kasukabe, Satoshi Miyata, Hirofumi Taki, Hideyuki Hasegawa, Hiroshi Kanai, Hiroaki Shimokawa

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

Objective - Left ventricular (LV) remodeling after acute myocardial infarction still remains an important issue in cardiovascular medicine. We have recently demonstrated that low-intensity pulsed ultrasound (LIPUS) therapy improves myocardial ischemia in a pig model of chronic myocardial ischemia through enhanced myocardial angiogenesis. In the present study, we aimed to demonstrate whether LIPUS also ameliorates LV remodeling after acute myocardial infarction and if so, to elucidate the underlying molecular mechanisms involved in the beneficial effects of LIPUS. Approach and Results - We examined the effects of LIPUS on LV remodeling in a mouse model of acute myocardial infarction, where the heart was treated with either LIPUS or no-LIPUS 3 times in the first week (days 1, 3, and 5). The LIPUS improved mortality and ameliorated post-myocardial infarction LV remodeling in mice. The LIPUS upregulated the expression of vascular endothelial growth factor, endothelial nitric oxide synthase, phosphorylated ERK, and phosphorylated Akt in the infarcted area early after acute myocardial infarction, leading to enhanced angiogenesis. Microarray analysis in cultured human endothelial cells showed that a total of 1050 genes, including those of the vascular endothelial growth factor signaling and focal adhesion pathways, were significantly altered by the LIPUS. Knockdown with small interfering RNA of either β1-integrin or caveolin-1, both of which are known to play key roles in mechanotransduction, suppressed the LIPUS-induced upregulation of vascular endothelial growth factor. Finally, in caveolin-1-deficient mice, the beneficial effects of LIPUS on mortality and post-myocardial infarction LV remodeling were absent. Conclusions - These results indicate that the LIPUS therapy ameliorates post-myocardial infarction LV remodeling in mice in vivo, for which mechanotransduction and its downstream pathways may be involved.

Original languageEnglish
Pages (from-to)1220-1229
Number of pages10
JournalArteriosclerosis, thrombosis, and vascular biology
Volume36
Issue number6
DOIs
Publication statusPublished - 2016 Jun 1

Keywords

  • caveolae
  • caveolin-1
  • integrins
  • myocardial infarction
  • myocardial ischemia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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