Cardiac hypertrophy is a critical intermediate step in the pathogenesis of heart failure. A myriad of signaling networks converge on cardiomyocytes to elicit hypertrophic growth in response to various injurious stimuli. In the present study, we investigated the cardiomyocyte-specific role of myocardin-related transcription factor A (MRTF-A) in angiotensin-II (Ang-II)-induced cardiac hypertrophy and the underlying mechanism. We report that conditional MRTF-A deletion in cardiomyocytes attenuated Ang-II-induced cardiac hypertrophy in mice. Similarly, MRTF-A knockdown or inhibition suppressed Ang-II-induced prohypertrophic response in cultured cardiomyocytes. Of note, Ang II treatment upregulated expression of phosphodiesterase 5 (PDE5), a known mediator of cardiac hypertrophy and heart failure, in cardiomyocytes, which was blocked by MRTF-A depletion or inhibition. Mechanistically, MRTF-A activated expression of specificity protein 1 (Sp1), which in turn bound to the PDE5 promoter and upregulated PDE5 transcription to promote hypertrophy of cardiomyocytes in response to Ang II stimulation. Therefore, our data unveil a novel MRTF-A-Sp1-PDE5 axis that mediates Ang-II-induced hypertrophic response in cardiomyocytes. Targeting this newly identified MRTF-A-Sp1-PDE5 axis may yield novel interventional solutions against heart failure.

Although percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) and bypass grafting are generally believed to be superior revascularization strategies in patients with coronary artery disease (CAD), the optimal strategy for diabetic patients is still controversial. This meta-analysis was performed to compare two methods of revascularization for patients with diabetes mellitus with left main coronary artery lesions or disease in multiple coronary arteries. Compared with the coronary artery bypass grafting (CABG) group, those receiving PCI-DES showed a greater risk of major adverse cardiovascular events (MACEs) (hazard ratio [HR]: 1.12, 95% confidence interval [CI]: 1.01–1.25, P = 0.03), major adverse cardiac and cerebrovascular events (MACCEs) (HR: 1.85, 95% CI: 1.58–2.16; P < 0.001), stroke (HR: 1.15, 95% CI: 1.02–1.29, P = 0.02), myocardial infarction (MI) (HR: 1.48, 95% CI: 1.04–2.09, P = 0.03), and repeat revascularization (HR: 3.23, 95% CI: 1.37–7.59, P = 0.007). CABG for diabetic patients with multivessel and/or left main CAD was superior to PCI-DES with regard to MACEs, MACCEs, MI, repeat revascularization and stroke, but there was no clear difference in all-cause mortality.

No abstract

No abstract

No abstract