miR-27a protects human mitral valve interstitial cell from TNF-alpha-induced inflammatory injury via up-regulation of NELL-1

MicroRNAs (miRNAs) have been reported to be associated with heart valve disease, which can be caused by inflammation. This study aimed to investigate the functional impacts of miR-27a on TNF-α-induced inflammatory injury in human mitral valve interstitial cells (hMVICs). hMVICs were subjected to 40 ng/mL TNF-α for 48 h, before which the expressions of miR-27a and NELL-1 in hMVICs were altered by stable transfection. Trypan blue staining, BrdU incorporation assay, flow cytometry detection, ELISA, and western blot assay were performed to detect cell proliferation, apoptosis, and the release of proinflammatory cytokines. We found that miR-27a was lowly expressed in response to TNF-α exposure in hMVICs. Overexpression of miR-27a rescued hMVICs from TNF-α-induced inflammatory injury, as cell viability and BrdU incorporation were increased, apoptotic cell rate was decreased, Bcl-2 was up-regulated, Bax and cleaved caspase-3/9 were down-regulated, and the release of IL-1β, IL-6, and MMP-9 were reduced. NELL-1 was positively regulated by miR-27a, and NELL-1 up-regulation exhibited protective functions during TNF-α-induced cell damage. Furthermore, miR-27a blocked JNK and Wnt/β-catenin signaling pathways, and the blockage was abolished when NELL-1 was silenced. This study demonstrated that miR-27a overexpression protected hMVICs from TNF-α-induced cell damage, which might be via up-regulation of NELL-1 and thus modulation of JNK and Wnt/β-catenin signaling pathways.

Morphological study of the human mitral-aortic intervalvular fibrosa

The mitral-aortic intervalvular fibrosa of the heart is of great clinical and surgical importance, because of its involvement in the anatomical and functional integrity of these two valves. In this work, we examined the morphology of the mitralaortic intervalvular fibrosa and its relationship to the mitral and aortic valves. Thirty formaldehyde-fixed adult human hearts of both sexes were dissected and the structural organization, dimensions and area of the mitral-aortic intervalvular fibrosa were determined. The mitral-aortic intervalvular fibrosa was a thin, translucent membranous area located between the root of the aortic artery and the left atrioventricular orifice. In most cases (63 por cento), the mitral-aortic intervalvular fibrosa was approximately triangular in shape, with an area of 93.9 ± 47.4 mm². The lower edge was associated with the anterior cusp of the mitral valve and was 18.0 ± 2.2 mm long, whereas the anterior edge was continuos with the left fibrous trigone and was 10.6 ± 3.0 mm long. The posterior edge was associated with the aortic wall and was continuos with the right fibrous trigone. This edge was 11.7 ± 3.4 mm long. These results may be useful for manufacturing protheses to substitute this injured membrane.