Inhibition of Epac1 suppresses mitochondrial fission and reduces neointima formation induced by vascular injury

Hui Wang, William G. Robichaux, Ziqing Wang, Fang C. Mei, Ming Cai, Guangwei Du, Ju Chen, Xiaodong Cheng

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Vascular smooth muscle cell (VSMC) activation in response to injury plays an important role in the development of vascular proliferative diseases, including restenosis and atherosclerosis. The aims of this study were to ascertain the physiological functions of exchange proteins directly activated by cAMP isoform 1 (Epac1) in VSMC and to evaluate the potential of Epac1 as therapeutic targets for neointima formation during vascular remodeling. In a mouse carotid artery ligation model, genetic knockdown of the Epac1 gene led to a significant reduction in neointima obstruction in response to vascular injury. Pharmacologic inhibition of Epac1 with an Epac specific inhibitor, ESI-09, phenocopied the effects of Epac1 null by suppressing neointima formation and proliferative VSMC accumulation in neointima area. Mechanistically, Epac1 deficient VSMCs exhibited lower level of PI3K/AKT signaling and dampened response to PDGF-induced mitochondrial fission and reactive oxygen species levels. Our studies indicate that Epac1 plays important roles in promoting VSMC proliferation and phenotypic switch in response to vascular injury, therefore, representing a therapeutic target for vascular proliferative diseases.

Original languageEnglish (US)
Article number36552
JournalScientific reports
Volume6
DOIs
StatePublished - Nov 10 2016
Externally publishedYes

ASJC Scopus subject areas

  • General

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