Journal Article

CD38 promotes angiotensin II‐induced cardiac hypertrophy

Wang, Xiao‐Lei, Wang, Jian‐Bin, Zhao, Ning, Hong, Xuan, Guan, Xiao‐Hui, Deng, Li‐Bin, Deng, Ke‐Yu, Chen, Ting‐Tao, Xin, Hong‐Bo, Xiao, Yun‐Fei, Liu, Xiao‐Hong, Fu, Mingui, Ji, Guang‐Ju

2017

Overview

Cardiac hypertrophy is an early hallmark during the clinical course of heart failure and regulated by various signalling pathways. Recently, we observed that mouse embryonic fibroblasts from CD38 knockout mice were significantly resistant to oxidative stress such as H2O2‐induced injury and hypoxia/reoxygenation‐induced injury. In addition, we also found that CD38 knockout mice protected heart from ischaemia reperfusion injury through activating SIRT1/FOXOs‐mediated antioxidative stress pathway. However, the role of CD38 in cardiac hypertrophy is not explored. Here, we investigated the roles and mechanisms of CD38 in angiotensin II (Ang‐II)‐induced cardiac hypertrophy. Following 14 days of Ang‐II infusion with osmotic mini‐pumps, a comparable hypertension was generated in both of CD38 knockout and wild‐type mice. However, the cardiac hypertrophy and fibrosis were much more severe in wild‐type mice compared with CD38 knockout mice. Consistently, RNAi‐induced knockdown of CD38 decreased the gene expressions of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) and reactive oxygen species generation in Ang‐II‐stimulated H9c2 cells. In addition, the expression of SIRT3 was elevated in CD38 knockdown H9c2 cells, in which SIRT3 may further activate the FOXO3 antioxidant pathway. The intracellular Ca2+ release induced by Ang‐II markedly decreased in CD38 knockdown H9c2 cells, which might be associated with the decrease of nuclear translocation of NFATc4 and inhibition of ERK/AKT phosphorylation. We concluded that CD38 plays an essential role in cardiac hypertrophy probably via inhibition of SIRT3 expression and activation of Ca2+‐NFAT signalling pathway. Thus, CD38 may be a novel target for treating cardiac hypertrophy.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: ADP-ribosyl Cyclase 1 - antagonists & inhibitors / ADP-ribosyl Cyclase 1 - deficiency / ADP-ribosyl Cyclase 1 - genetics / AKT protein / Angiotensin / Angiotensin II / Angiotensin II - pharmacology / Animals / Atrial Natriuretic Factor - genetics / Atrial Natriuretic Factor - metabolism / Atrial natriuretic peptide / Brain natriuretic peptide / Calcium (intracellular) / Calcium - metabolism / Calcium signalling / cardiac hypertrophy / Cardiomegaly - chemically induced / Cardiomegaly - genetics / Cardiomegaly - metabolism / Cardiomegaly - pathology / CD38 / CD38 antigen / Cell Line / Embryo fibroblasts / Embryos / Fibrosis / Forkhead Box Protein O3 - genetics / Forkhead Box Protein O3 - metabolism / FOXO3 protein / Gene Expression Regulation / Heart diseases / Hydrogen peroxide / Hypertrophy / Hypoxia / Ischemia / Membrane Glycoproteins - antagonists & inhibitors / Membrane Glycoproteins - deficiency / Membrane Glycoproteins - genetics / Mice / Mice, Knockout / Mitogen-Activated Protein Kinase 1 - genetics / Mitogen-Activated Protein Kinase 1 - metabolism / Mitogen-Activated Protein Kinase 3 - genetics / Mitogen-Activated Protein Kinase 3 - metabolism / Myocardium - metabolism / Myocardium - pathology / Myocytes, Cardiac - drug effects / Myocytes, Cardiac - metabolism / Myocytes, Cardiac - pathology / Natriuretic Peptide, Brain - genetics / Natriuretic Peptide, Brain - metabolism / Nerve Tissue Proteins - genetics / Nerve Tissue Proteins - metabolism / NF-AT protein / NFATC Transcription Factors - genetics / NFATC Transcription Factors - metabolism / NFATc4 / Nuclear transport / Original / Oxidative stress / Phosphorylation / Proto-Oncogene Proteins c-akt - genetics / Proto-Oncogene Proteins c-akt - metabolism / Rats / Reactive oxygen species / Reactive Oxygen Species - metabolism / Reperfusion / RNA, Small Interfering - genetics / RNA, Small Interfering - metabolism / Rodents / Signal Transduction / SIRT3 / Sirtuins - genetics / Sirtuins - metabolism