Key result
Increasing cAMP improves cardiac function and inhibits CTGF via p44/42MAPK signaling in MI mice.
Why the study?
To investigate the regulation of the cyclic adenosine monophosphate (cAMP) signaling pathway on connective tissue growth factor during myocardial fibrosis in mice after myocardial infarction.
Does activation of the cAMP signaling pathway improve cardiac function and reduce CTGF expression in a mouse model of myocardial infarction?
Does activation of the cAMP signaling pathway improve cardiac function and reduce CTGF expression in a mouse model of myocardial infarction?
Activation of the cAMP signaling pathway improves cardiac function and attenuates myocardial fibrosis after myocardial infarction in mice by downregulating CTGF expression.
Hypothesis-generating in mouse MI; leaves open cAMP pathway effects in patients.
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.
No takes yet. Share an insight, caveat, or question.
Zhao et al. (2021) studied Myocardial fibrosis after myocardial infarction. Meglumine adenosine cyclophosphate (MAC) and forskolin vs. MI alone or TGF-β1 alone was evaluated on Cardiac function indices and CTGF expression. Increasing cAMP levels with meglumine adenosine cyclophosphate or forskolin improved cardiac function and inhibited CTGF expression via the p44/42MAPK signaling pathway in a mouse model of MI.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: