EndophilinA2 protects against angiotensin II‐induced cardiac hypertrophy by inhibiting angiotensin II type 1 receptor trafficking in neonatal rat cardiomyocytes

Abstract

Cardiac hypertrophy is one of the major risk factors for chronic heart failure. The role of endophilinA2 (EndoA2) in clathrin-mediated endocytosis and clathrin-independent endocytosis is well documented. In the present study, we tested the hypothesis that EndoA2 protects against angiotensin II (Ang II)-induced cardiac hypertrophy by mediating intracellular angiotensin II type 1 receptor (AT1-R) trafficking in neonatal rat cardiomyocytes (NRCMs). Cardiac hypertrophy was evaluated by using cell surface area and quantitative RT-PCR (qPCR) analyses. For the first time, we found that EndoA2 attenuated cardiac hypertrophy and fibrosis induced by Ang II. Moreover, EndoA2 inhibited apoptosis induced by excessive endoplasmic reticulum stress (ERS), which accounted for the beneficial effects of EndoA2 on cardiac hypertrophy. We further revealed that there was an interaction between EndoA2 and AT1-R.The expression levels of EndoA2, which inhibits AT1-R transport from the cytoplasm to the membrane, and the interaction between EndoA2 and AT1-R were obviously decreased after Ang II treatment. Furthermore, Ang II inhibited the co-localization of AT1-R with GRP-78, which was reversed by EndoA2 overexpression. In conclusion, our results suggested that EndoA2 plays a role in protecting against cardiac hypertrophy induced by Ang II, possibly by inhibiting AT1-R transport from the cytoplasm to the membrane to suppress signal transduction.

Endophilin A2-mediated alleviation of endoplasmic reticulum stress-induced cardiac injury involves the suppression of ERO1α/IP3R signaling pathway

“…This observation has made a significant contribution to our understanding of the role of endophilin family in cardiovascular diseases, which has never been examined before. Our following-up studies on EndoA2 further confirmed the critical role of EndoA2 in heart diseases [19][20][21]. However, the role of EndoA2 in MI remains poorly understood.…”

“…EndoA2, which was originally identified as a fusion partner of mixed-lineage leukemia gene in childhood leukemia [32], is involved in vesicle endocytosis. Our previous study verified that EndoA2 promoted H 2 O 2 -induced rat basilar artery smooth muscle cell apoptosis [18], Moreover, EndoA2 inhibited H 2 O 2 -induced H9C2 cardiomyocyte apoptosis by enhancing autophagy [21] and attenuated cardiac hypertrophy induced by angiotensin II [20] or isoproterenol [19]. However, whether EndoA2 plays a key role in myocardial ischemic injury is not clear.…”

“…Although we have demonstrated that EndoA2 attenuates cardiac hypertrophy in our recently published studies [19,20], its potential in cardiac protection in response to myocardial ischemic injury has not been well characterized. Here, we established an MI mouse model by ligating the LAD coronary artery.…”

Inhibiting SLC26A4 reverses cardiac hypertrophy in H9C2 cells and in rats

“…In our study, cardiac hypertrophy was successfully induced by 200 µM PE in vitro. Myocardial fibrosis is usually accompanied by cardiac hypertrophy, which has become an important pathophysiological characteristic of the development of cardiac hypertrophy (Liu et al, 2018b). In this study, we found that the expression of myocardial fibrosis-related protein α-SMA was elevated in myocardial cells treated with PE.…”

Cholecystokinin Expression in the Development of Myocardial Hypertrophy

“…The clinical study also reported MH is associated with morbidity and mortality of patients [ 18 ]. As research has progressed, we have found that many factors are related to MH and affect the process of MH, such as sex difference [ 19 ], fat diet [ 20 ], testosterone [ 21 ], angiotensin II [ 22 ], isoproterenol [ 23 ], and leptin [ 24 ].…”