MicroRNA-497 Inhibits Cardiac Hypertrophy by Targeting Sirt4

Abstract

Cardiac hypertrophy is an adaptive enlargement of the myocardium in response to overload pressure of heart. From abundant studies, a conclusion is drawn that many microRNAs (miRNAs) are associated with cardiac hypertrophy and heart failure. To investigate the role of microRNA-497 (miR-497) in myocardial hypertrophy, two models were established in this study from cell level to integral level. Cardiac hypertrophy was induced by using angiotensin Ⅱ (Ang Ⅱ) in vitro and was created by transverse abdominal aortic constriction (TAC) in vivo. There was a significant decrease expression of miR-497 in cardiac hypertrophy models. Moreover, overexpression of miR-497 inhibited myocardial hypertrophy both in vitro and in vivo without heart function variation. In addition, luciferase reporter assays demonstrated that Sirt4 was a direct target gene of miR-497. Taking together, our study indicates that miR-497 modulates cardiac hypertrophy by targeting Sirt4 and may serve as a potential therapeutic substance in the course.

miR‐376b‐3p attenuates mitochondrial fission and cardiac hypertrophy by targeting mitochondrial fission factor

“…Thus, it provides new evidences to explore the functions of miRNAs in modulating mitochondrial function. For instance, miR‐106a accelerates cardiac hypertrophy via restraining mitofusin 2, miR‐497 and miR‐485‐5p attenuate cardiac hypertrophy by targeting Sirt4 and MAPL, respectively . In present study, we found that miRNA‐miR‐376b‐3p negatively regulate mitochondrial fission in cardiac hypertrophic NRVCs by targeting MFF.…”

“…For instance, miR-106a accelerates cardiac hypertrophy via restraining mitofusin 2, 30 miR-497 and miR-485-5p attenuate cardiac hypertrophy by targeting Sirt4 and MAPL, respectively. 26,31 In present study, we found that miRNA-miR-376b-3p negatively regulate mitochondrial fission in cardiac hypertrophic NRVCs by targeting MFF. miR-376b plays major roles in regulating of various biology activities including cancer, 32,33 liver regeneration, 34 angiogenesis 35 and cardioprotection.…”

Novel heart failure biomarkers: why do we fail to exploit their potential?

“…Only later, a link between activation of the fetal gene program, miRNAs, and HF development was suggested [160][161][162]. For some solitary miRNAs, a role in pathological cardiac remodeling in animal models was found [160,[163][164][165][166]. Also, in humans, the relationship between miRNAs and cardiac remodeling has been investigated.…”

Emerging potential benefits of modulating NAD+metabolism in cardiovascular disease

“…This study (65) demonstrated that SIRT4 overexpression increased oxidative stress by inhibiting SIRT3 binding and deacetylation of manganese SOD, an important mediator in scavenging ROS. In addition, suppression of SIRT4 by miRNA-497 overexpression diminished the adverse hypertrophic response induced by transverse aortic constriction in mice (106). Furthermore, knockdown of SIRT4 was shown to improve metabolic functions by upregulating FAO metabolism in myocytes and hepatocytes, further suggesting that SIRT4 may be detrimental to the heart (48,72).…”