Division of Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.
Department of Medicine, Duke University, Durham, 27710, NC, USA.
Sci Rep. 2018 Jan 15;8(1):761. doi: 10.1038/s41598-017-19136-6.
Peripheral ischemia is associated with higher degree of endothelial dysfunction and a worse prognosis after percutaneous coronary interventions (PCI). However, the role of peripheral ischemia on vascular remodeling in remote districts remains poorly understood. Here we show that the presence of hindlimb ischemia significantly enhances neointima formation and impairs endothelial recovery in balloon-injured carotid arteries. Endothelial-derived microRNAs are involved in the modulation of these processes. Indeed, endothelial miR-16 is remarkably upregulated after vascular injury in the presences of hindlimb ischemia and exerts a negative effect on endothelial repair through the inhibition of RhoGDIα and nitric oxide (NO) production. We showed that the repression of RhoGDIα by means of miR-16 induces RhoA, with consequent reduction of NO bioavailability. Thus, hindlimb ischemia affects negative carotid remodeling increasing neointima formation after injury, while systemic antagonizzation of miR-16 is able to prevent these negative effects.
外周缺血与经皮冠状动脉介入治疗（PCI）后更高程度的内皮功能障碍和更差的预后相关。然而，外周缺血对远程区域血管重塑的作用仍知之甚少。在这里，我们发现后肢缺血的存在显著增强了球囊损伤颈动脉中的新生内膜形成，并损害了内皮细胞的恢复。内皮衍生的 microRNAs 参与了这些过程的调节。事实上，在内皮损伤后，在存在后肢缺血的情况下，内皮 miR-16 显著上调，并通过抑制 RhoGDIα 和一氧化氮（NO）的产生对内皮修复产生负性影响。我们表明，通过 miR-16 抑制 RhoGDIα 诱导 RhoA，从而导致 NO 生物利用度降低。因此，后肢缺血影响了颈动脉的负性重塑，增加了损伤后的新生内膜形成，而全身性拮抗 miR-16 能够预防这些负性影响。
