Qiliqiangxin Attenuates Phenylephrine-Induced Cardiac Hypertrophy through Downregulation of MiR-199a-5p

Abstract

Background/Aims: Qiliqiangxin (QL), a traditional Chinese medicine, has long been used to treat chronic heart failure. Previous studies demonstrated that QL could prevent cardiac remodeling and hypertrophy in response to hypertensive or ischemic stress. However, little is known about whether QL could modulate cardiac hypertrophy in vitro, and (if so) whether it is through modulation of specific hypertrophy-related microRNA. Methods: The primary neonatal rat ventricular cardiomyocytes were isolated, cultured, and treated with phenylephrine (PE, 50 µmol/L, 48 h) to induce hypertrophy in vitro, in the presence or absence of pretreatment with QL (0.5 µg/ml, 48 h). The cell surface area was determined by immunofluorescent staining for α-actinin. The mRNA levels of hypertrophic markers including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (MYH7) were assayed by qRT-PCRs. The protein synthesis of cardiomyocytes was determined by the protein/DNA ratio. The miR-199a-5p expression level was quantified in PE-treated cardiomyocytes and heart samples from acute myocardial infarction (AMI) mouse model. MiR-199a-5p overexpression was used to determine its role in the anti-hypertrophic effect of QL on cardiomyocytes. Results: PE induced obvious enlargement of cell surface in cardiomyocytes, paralleling with increased ANP, BNP, and MYH7 mRNA levels and elevated protein/DNA ratio. All these changes were reversed by the treatment with QL. Meanwhile, miR-199a-5p was increased in AMI mouse heart tissues. Of note, the increase of miR-199a-5p in PE-treated cardiomyocytes was reversed by the treatment with QL. Moreover, overexpression of miR-199a-5p abolished the anti-hypertrophic effect of QL on cardiomyocytes. Conclusion: QL prevents PE-induced cardiac hypertrophy. MiR-199a-5p is increased in cardiac hypertrophy, while reduced by treatment with QL. miR-199a-5p suppression is essential for the anti-hypertrophic effect of QL on cardiomyocytes.

Targeting Peroxisome Proliferator Activated Receptor α (PPAR α) for the Prevention of Mitochondrial Impairment and Hypertrophy in Cardiomyocytes

“…Growing evidences suggest that microRNAs (miRNAs) are important mediators of cellular signaling and play crucial roles in cardiac hypertrophy and heart failure [22,23]. miRNAs are highly conserved class of small non coding single stranded RNAs with approximate length of 18-25 nucleotides.…”

Myocardial microRNAs associated with reverse remodeling in human heart failure

“…In addition, miR-1 blocks β-adrenergic-mediated hypertrophy in adult mouse hearts through target-specific repression of calmodulin and NFAT activity, plus repression of the hypertrophic transcription factor MEF2 (27). miR-199a-5p was downregulated in Rs versus baseline and versus NRs, and decreased levels of miR-199a-5p are associated with the attenuation of pathologic cardiac myocyte hypertrophy (28), as well as in the induction of physiologic hypertrophy and maintenance of cardiac homeostasis (29). miR-208b-3p, selectively decreased in Rs compared with baseline at 12 months, is involved in the mediation of myocardial hypertrophy (30).…”

Advances in Research on the circRNA‐miRNA‐mRNA Network in Coronary Heart Disease Treated with Traditional Chinese Medicine

“…Some circRNAs have been shown to act as miRNA sponges, to interact with RNA-binding proteins, to regulate transcription, or to be translated into proteins. CircRNAs have been widely explored in antiaging strategies, diabetes, cardiovascular diseases, and malignant tumors [44][45][46][47][48][49][50]. In various cardiovascular tissues and organs, circRNA participates in physiological and pathological processes such as myocardial repair regulation and fibrosis of vascular smooth muscle cells and myocardium, without e circRNA-miRNA network may regulate mRNA participating in the development of CHD through competitive endogenous RNA (ceRNA).…”