Cyclic adenosine monophosphate regulates connective tissue growth factor expression in myocardial fibrosis after myocardial infarction

Abstract

Objective This study aimed to investigate regulation of the cyclic adenosine monophosphate (cAMP) signaling pathway on connective tissue growth factor (CTGF) during myocardial fibrosis (MF) in mice after myocardial infarction (MI). Methods An MI mouse model was established and cardiac function indices were detected by ultrasound. Quantitative reverse transcription polymerase chain reaction and western blotting were used to determine CTGF and transforming growth factor β1 (TGF-β1) cardiac expression. Mouse cardiac fibroblasts (MCFs) were used to study the mechanism of MF after MI. Results Cardiac function indices were lower after MI. Cardiac function indices were better in the MI + meglumine adenosine cyclophosphate (MAC) group than in the MI group, and CTGF expression in the MI + MAC group was downregulated. TGF-β1 expression was not different among the MI groups. Forskolin increased intracellular cAMP levels and inhibited CTGF expression in MCFs. Expression of p44/42 mitogen-activated protein kinase (MAPK) was significantly lower in the TGF-β1 + forskolin group than in the TGF-β1 group, while protein kinase A was significantly upregulated. CTGF expression was significantly lower in the TGF-β1 + forskolin + PD98509 group than in the TGF-β1 + forskolin group. Conclusions This study shows that cAMP upregulates protein kinase A expression through the p44/42MAPK signaling pathway and decreases p44/42MAPK phosphorylation levels, inhibiting CTGF expression.