Abstract
Background: Heart failure (HF) is a major public health problem worldwide. The development of HF was related to coronary microvessel dysfunction. Whether miRNAs participate in HF by regulating coronary microvessel function remain unclear.Methods: The potential targets of miR-665 were predicted by rnahybrid software, then verified through anti-Ago2 co-immunoprecipitation, Western blotting and luciferase reporter assays. rAAV9 system was used to manipulate the expression of miR-665 in vivo.Results: Significant increase of miR-665 was observed in endothelial cells of human heart with heart failure. In vitro over-expression of miR-665 in endothelial cells resulted in decreased proliferation but enhanced apoptosis. rAAV-mediated delivery of miR-665 reduced coronary microvessel angiogenesis and cardiac microvessel density, then further impaired cardiac function in vivo. Furthermore, CD34 was confirmed as one of the miR-665 targets. Consistently, re-expression of CD34 attenuated miR-665-mediated damage effects in vitro and in vivo. We also found that Sp1 regulated miR-665 expression in endothelial cells.Conclusion: Our findings demonstrated that miR-665 played an important role in heart failure via damaging coronary microvessel angiogenesis, and suggested that miRNA-based therapeutics may protect against coronary microvessel dysfunction and heart failure.
Highlights
Heart failure (HF) is a major public health problem, which is defined as a complex syndrome that results from various structural or functional impairment of ventricular filling or ejection of blood [1]
Our previous work reported that miR-665 was upregulated in the heart and plasma of chronic heart failure (CHF) patients [11], which indicated that miR-665 may participate in heart failure
RNA fluorescence in situ hybridization demonstrated that the endogenous miR-665 was enriched in CD31-positive microvessels of human left ventricular (LV) specimens, and significantly increased miR-665 was observed in human hearts with heart failure (Figure 1A)
Summary
Heart failure (HF) is a major public health problem, which is defined as a complex syndrome that results from various structural or functional impairment of ventricular filling or ejection of blood [1]. The imbalance between coronary angiogenesis and cardiomyocyte growth participates in cardiac function regulation, and impaired vasculature may contribute to the transition from compensated to decompensated cardiac hypertrophy, and lead to heart failure [5]. Results: Significant increase of miR‐665 was observed in endothelial cells of human heart with heart failure. RAAV‐mediated delivery of miR‐665 reduced coronary microvessel angiogenesis and cardiac microvessel density, further impaired cardiac function in vivo. Conclusion: Our findings demonstrated that miR‐665 played an important role in heart failure via damaging coronary microvessel angiogenesis, and suggested that miRNA‐based therapeutics may protect against coronary microvessel dysfunction and heart failure
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
