C1QTNF1 attenuates angiotensin II-induced cardiac hypertrophy via activation of the AMPKa pathway.

摘要: Abstract Rationale Complement C1q tumor necrosis factor related proteins (C1QTNFs) have been reported to diverse biological influence on the cardiovascular system. C1QTNF1 is a member of CTRP superfamily. expressed in myocardium; however, its function myocytes has not yet investigated. Objective To systematically investigate roles angiotensin II (Ang II)-induced cardiac hypertrophy. Methods and results knock-out mice were used with aim determining role hypertrophy adult heart. Data from experiments showed that was up-regulated during hypertrophic processes, which triggered by increased reactive oxygen species. deficiency accelerated hypertrophy, fibrosis, inflammation responses, oxidative stress deteriorating dysfunction Ang II-induced mouse model. We identified as negative regulator cardiomyocyte II-stimulated neonatal rat cardiomyocytes using recombinant human globular domain siRNA. Injection also suppressed response vivo. The anti-hypertrophic effects rely AMPKa activation, inhibits mTOR P70S6K phosphorylation. An inhibitor abrogated both vivo vitro. Moreover, C1QTNF1-mediated activation inhibition PDE1-4, subsequently activated cAMP/PKA/LKB1 pathway. Conclusion Our demonstrated improves fibrosis increasing activating AMPKa, suggesting could be therapeutic target for heart failure.