MiR-195 inhibits myocardial fibrosis in hypertensive rats by regulating TGFß1-Smad3 signaling pathway.

The article "MiR-195 inhibits myocardial fibrosis in hypertensive rats by regulating TGFß1-Smad3 signaling pathway, by Q. Xu, X.-X. Lin, P. Liu, W. Zhang, K. Tang, Y.-S. Zhai, L.-J. Liu, W.-Y. Mei, published in Eur Rev Med Pharmacol Sci 2019; 23 (18): 8087-8094-DOI: 10.26355/eurrev_201909_19026-PMID: 31599435" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19026.

MiR-195 inhibits myocardial fibrosis in hypertensive rats by regulating TGFß1-Smad3 signaling pathway.

OBJECTIVE: The aim of this study was to investigate the effect of micro-ribonucleic acid-195 (miR-195) on myocardial fibrosis in hypertensive rats through the transforming growth factor beta 1 (TGFß1)-Smad3 signaling pathway. MATERIALS AND METHODS: Spontaneously hypertensive rats (SHRs) were selected in this study to establish the animal model. The content of miR-195 in the model group and control group was measured, respectively. Arterial blood pressure, liver function and myocardial function in the two groups were detected and examined. Pathological changes in rat myocardial tissues were detected via hematoxylin-eosin (HE) staining. After that, myocardial fibroblasts were collected and added with miRNA inhibitors and mimics to suppress and overexpress miR-195. Thereafter, Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting were employed to detect the mRNA and protein expression levels of checkpoint kinase 1 (Chek1) and alpha-smooth muscle actin (α-SMA) (important molecules for proliferation and differentiation of myocardial fibroblasts), as well as the related pathway TGFß1-Smad3. Furthermore, the effects of miR-195 on myocardial fibrosis in hypertensive rats via the TGFß1-Smad3 signaling pathway were comprehensively observed. RESULTS: Serum alkaline phosphatase (ALP), glutamic pyruvic aminotransferase (ALT) and creatine kinase (CK) levels in the SHR group were significantly higher than those of the normal group. Cardiac function examination showed that SHR group had significantly reduced fractional shortening (FS, %) and ejection fraction (EF, %) in comparison with the normal group. However, systolic blood pressure, diastolic blood pressure, left ventricular end-diastolic dimension (LVEDd) and left ventricular end-systolic dimension (LVESd) were markedly elevated in the SHR group. In addition, the miR-195 expression level was remarkably reduced in hypertensive rats. Histopathological changes in rat myocardial tissues were detected through HE staining. The results showed that the normal group had orderly arranged myocardial cells. However, SHR group showed disorderly arranged myocardial cells, thickened myocardial fibers and myocardial fibrosis. RT-PCR assay results revealed that the mRNA levels of Collagen, Chek1, α-SMA, TGFß1 and Smad3 in rat myocardial fibroblasts were significantly reduced in Mimics group (p<0.05) and increased in Inhibitors group (p<0.05). Western blotting results demonstrated that, compared with the control group, the protein levels of α-SMA, TGFß1 and Smad3 in rat myocardial cells decreased significantly in Mimics group (p<0.05). Opposite results were observed in Inhibitors group (p<0.05). The above results suggested that overexpression of miR-195 inhibited the expressions of TGFß1-Smad3 signaling pathway and related molecules, further repressing myocardial fibrosis. CONCLUSIONS: MiR-195 participates in the development and progression of myocardial fibrosis in hypertensive rats through the TGFß1-Smad3 signaling pathway. Furthermore, this can inhibit the development of myocardial fibrosis in hypertensive rats and prevent myocardial diseases.

[Effect of asymmetrical dimethylarginine for predicting pro-thrombotic risk in atrial fibrillation].

OBJECTIVE: Atrial fibrillation (AF) is responsible for some thromboembolic events. Asymmetrical dimethylarginine(ADMA) increases in atrial fibrillation(AF) animals with dysfunction of endothelium, but its role in pro-thrombotic state of AF was unknown. The aim of our study was to explore the role of ADMA in predicting the pro-thrombotic state in AF and to reveal its mechanism. METHODS: One hundred and thirty-eight patients in the First Affiliated Hospital, Sun Yat-sen University, from 2010 to 2012, were enrolled (persistent atrial fibrillation group, PAF, n=80; paroxysmal atrial fibrillation group, Paf, n=30; sinus rhythm, SR, n=28). Plasma ADMA levels were detected by ELISA-kits. CHADS2 and CHA2DS2-VASc scores were estimated for each patient.14 Beagles (pacing group, n=8; sham group, n=6) were subjected to rapid atrial pacing (RAP). ADMA level was detected after 4 weeks of RAP. RESULTS: ADMA level was elevated significantly in patients with atrial fibrillation especially in patients with persistent atrial fibrillation, and showed a significant linear correlation to CHADS2 and CHA2DS2-VASc score. With ADMA, ROC area under the curve was 0.865 in CHADS2 score ≥2 and was 0.959 in CHA2DS2-VASc score ≥2 (P<0.001 respectively). After 4 weeks of RAP, ADMA level was elevated compared to sham group and before operation. ADMA showed a linear correlation with atrial fibrillation susceptibility(r=0.686, P=0.007). CONCLUSIONS: ADMA levels are elevated both in AF patients and RAP beagles. ADMA correlates with stroke risk concerning with CHADS2/CHA2DS2-VASc score. ADMA may become a new biomarker for predicting pro-thrombotic risk in AF.