Buyang Huanwu Decoction promotes angiogenesis in myocardial infarction through suppression of PTEN and activation of the PI3K/Akt signalling pathway

Abstract

Ethnopharmacological relevanceMyocardial infarction (MI) is the most severe subtype of coronary artery disease. Recent studies have demonstrated that the repair process and prognosis of MI are closely related to microcirculatory function in myocardial tissue. Buyang Huanwu Decoction (BYHWD) has shown great potential in the treatment of MI. However, the effects and mechanisms of BYHWD on angiogenesis post-MI remain unclear. Aim of the studyThe study aimed to explore the promotion of angiogenesis by BYHWD post-MI and the potential mechanisms in vivo and in vitro. Materials and methodsMI in mice was induced by permanent ligature of the coronary artery. The sample was divided into sham, model, and BYHWD treatment groups. After four weeks, the effects of BYHWD treatment on cardiac function were evaluated by echocardiography and HE and Masson staining. Angiogenesis was detected by CD 31 immunofluorescence staining in vivo. Then, various databases were searched to identify the corresponding targets of BYHWD in order to explore the molecular mechanisms underlying its effects in MI. Moreover, Western blot and immunohistochemistry were employed to measure the PTEN/PI3K/Akt/GSK3β signalling pathway and VEGFA expression in MI mice. Finally, the effects of BYHWD on cell angiogenesis and the activation of the PTEN/PI3K/Akt/GSK3β pathway in primary HUVECs were investigated. Overexpression of PTEN was achieved by an adenovirus vector encoding PTEN. ResultsBYHWD significantly promoted angiogenesis and improved cardiac function in MI mice. Target prediction analysis suggested that BYHWD ameliorates MI via the PI3K/Akt pathway. BYHWD promoted angiogenesis post-MI by suppressing PTEN and activating the PI3K/Akt/GSK3β signalling pathway in vivo and in vitro. Moreover, the effects of BYHWD on HUVEC angiogenesis and the expression of PI3K/Akt/GSK3β signalling pathway-associated proteins were partially abrogated by the overexpression of PTEN. ConclusionCollectively, this study demonstrates that BYHWD exerts cardioprotective effects against MI by targeting angiogenesis. These effects are related to suppressing PTEN and activating the PI3K/Akt/GSK3β signalling pathway by BYHWD.