The miR-214-3p/c-Ski axis modulates endothelial-mesenchymal transition in human coronary artery endothelial cells in vitro and in mice model in vivo.

Cardiovascular disease (CVD) is a leading non-communicable disease with a high fatality rate worldwide. Hypertension, a common cardiovascular condition, is a significant risk factor for the development of heart failure because the activation of the renin-angiotensin system (RAS) is considered to be the major promoting reason behind myocardial fibrosis (MF). In this study, Angiotensin II (Ang II) stimulation-induced endothelial to mesenchymal transition (End-MT) in HCAECs, including the decrease of CD31 level, the increase of α-SMA, collagen I, slug, snail, and TGF-ß1 levels, and the promotion of Smad2/3 phosphorylation. Meanwhile, the c-Ski level was reduced in Ang II-stimulated HCAECs. In HCAECs, Ang II-induced changes could be partially attenuated by c-Ski overexpression. miR-214-3p directly targeted c-Ski and inhibited c-Ski expression. Moreover, miR-214-3p inhibition reduced Ang II-caused End-MT in HCAECs. miR-214-3p overexpression further enhanced Ang II-induced End-MT, while c-Ski overexpression could markedly reverse the effects of miR-214-3p overexpression. In the Ang II-induced mouse cardiac hypertrophic model, Ang II-caused increase of cellular cross-sectional area and cardiac fibrosis were partially ameliorated by LV-c-Ski; when mice were co-treated with LV-c-Ski and agomir-214-3p, the beneficial effects of LV-c-Ski were reversed. In conclusion, the miR-214-3p/c-Ski axis modulated Ang II-induced End-MT in HCAECs and cardiac hypertrophy and fibrosis in the mice model.

NR4A3 induces endothelial dysfunction through up-regulation of endothelial 1 expression in adipose tissue-derived stromal cells.

Hypertension is one of the most prevalent diseases worldwide. Increased synthesis of the vasoconstrictor peptide endothelin 1 (encoded by EDN1) might be responsible for high blood pressure. The present study further confirmed the abnormal EDN1 upregulation within adipose tissue-derived stromal cells (ADSCs) derived from morbidly obese subjects. The overexpression of EDN1 in ADSCs derived from non-obese subjects significantly promoted the proliferation and migration of HUVECs and tube formation by human umbilical vein endothelial cell (HUVEC). Transcription factor NR4A3 was positively correlated with EDN1, binding to EDN1 promoter region to upregulate EDN1 expression. Similarly, the overexpression of NR4A3 in ADSCs derived from non-obese subjects significantly promoted the proliferation and migration of HUVECs and tube formation by HUVECs, as well as EDN1 protein levels in ADSCs. However, the effects of NR4A3 overexpression on EDN1 protein levels in ADSCs and the proliferation and migration of HUVECs and tube formation by HUVECs were significantly reversed by EDN1 silencing in ADSCs. In conclusion, NR4A3 is abnormally upregulated in ADSCs derived from morbidly obese subjects; NR4A3 could promote HUVEC angiogenesis through binding to EDN1 promoter and upregulating EDN1 expression.

Cox-2 promotes mesenchymal stem cells differentiation into cardiocytes by activating JNK and ERK pathway.

Coronary heart disease and various cardiomyopathys may cause myocardial damage, reducing the number of myocardial cells with complete functions. Cyclooxygenase 2 (Cox-2) has been reported participating in a variety of pathological processes, including tumor invasion and metastasis. In this study, we sought to explore the correlation of Cox-2 with MSCs proliferation, and migration. MSCs were transfected with pcDNA-Cox2 and NS-398 to promote or inhibit the expression of Cox2. Then, MTT, transwell, qRT-PCR and western blot were used to test the influence of Cox2 on cells proliferation, cells migration and cell viability of mesenchymal stem. The results show that Cox-2 promotes directional differentiation of myocardial cells and the overexpression of cox-2 can activate the key factors of JNK and ERK signaling pathway, promotes myocardial cell directional differentiation.