RESUMO
Heart valve diseases are usually treated by surgical intervention addressed for the replacement of the damaged valve with a biosynthetic or mechanical prosthesis. Although this approach guarantees a good quality of life for patients, it is not free from drawbacks (structural deterioration, nonstructural dysfunction, and reintervention). To overcome these limitations, the heart valve tissue engineering (HVTE) is developing new strategies to synthesize novel types of valve substitutes, by identifying efficient sources of both ideal scaffolds and cells. In particular, a natural matrix, able to interact with cellular components, appears to be a suitable solution. On the other hand, the well-known Wharton's jelly mesenchymal stem cells (WJ-MSCs) plasticity, regenerative abilities, and their immunomodulatory capacities make them highly promising for HVTE applications. In the present study, we investigated the possibility to use porcine valve matrix to regenerate in vitro the valve endothelium by WJ-MSCs differentiated along the endothelial lineage, paralleled with human umbilical vein endothelial cells (HUVECs), used as positive control. Here, we were able to successfully decellularize porcine heart valves, which were then recellularized with both differentiated-WJ-MSCs and HUVECs. Data demonstrated that both cell types were able to reconstitute a cellular monolayer. Cells were able to positively interact with the natural matrix and demonstrated the surface expression of typical endothelial markers. Altogether, these data suggest that the interaction between a biological scaffold and WJ-MSCs allows the regeneration of a morphologically well-structured endothelium, opening new perspectives in the field of HVTE.
RESUMO
BACKGROUND: MicroRNAs (miRNAs) are endogenous, non-coding, short, single-stranded RNAs and represent a new class of gene regulators. Recent evidence supports a role for miRNAs in cardiovascular pathophysiology and atherosclerosis development. We have previously demonstrated that miR-145 is widely expressed in human atherosclerotic lesions and its downregulation has been correlated with vascular smooth muscle cell dedifferentiation, a cardinal step in the development of atherosclerosis. However, no evidences are available at this time about modulation of miR-145 in the setting of hypertension. Thus, the aim of this study was to investigate the expression of miR-145 in complicated hypertension. MATERIALS AND METHODS: Atherosclerotic plaques were obtained from 22 patients undergoing carotid endarterectomy for high-grade internal carotid artery stenosis. Plaques were subdivided into hypertension (n = 15) and control (n = 7) groups according to the presence or absence of hypertension (as defined by blood pressure > 140/90 mmHg or current antihypertensive treatment). In study plaques, miR-145 values were evaluated using real-time PCR. The level of induction has been tested by using ΔΔ cycle threshold method. RESULTS: We found that miR-145 was significantly more expressed in atherosclerotic plaques of hypertensive patients than in control plaques (1.201 ± 0.260 vs 0.483 ± 0.148 fold induction ± SE; p = 0.026). Moreover, a post-hoc analysis showed that treatment with angiotensin receptor blockers may be associated with the maximum increase in miR-145 levels, although these data did not show any statistical significance probably due to the limited sample size. CONCLUSIONS: To the best of our knowledge, this study is the first demonstration that hypertension may upregulate miR-145 expression in human atherosclerotic plaques. Future investigations will be necessary to establish the molecular readout of miR-145 upregulation in atherosclerotic lesions in hypertension.