Bartoli-Leonard Francesca, Wilkinson Fiona L, Langford-Smith Alex W W, Alexander M Y, Weston Ria
Translational Cardiovascular Science, Centre for Bioscience, Manchester Metropolitan University, Manchester, United Kingdom.
Front Cardiovasc Med. 2018 Dec 18;5:183. doi: 10.3389/fcvm.2018.00183. eCollection 2018.
Vascular calcification is a major health risk and is highly correlated with atherosclerosis, diabetes, and chronic kidney disease. The development of vascular calcification is an active and complex process linked with a multitude of signaling pathways, which regulate promoters and inhibitors of osteogenesis, the balance of which become deregulated in disease conditions. SIRT1, a protein deacetylase, known to be protective in inhibiting oxidative stress and inflammation within the vessel wall, has been shown as a possible key player in modulating the cell-fate determining canonical Wnt signaling pathways. Suppression of SIRT1 has been reported in patients suffering with cardiovascular pathologies, suggesting that the sustained acetylation of osteogenic factors could contribute to their activation and in turn, lead to the progression of calcification. There is clear evidence of the synergy between β-Catenin and elevated Runx2, and with Wnt signaling being β-Catenin dependent, further understanding is needed as to how these molecular pathways converge and interact, in order to provide novel insight into the mechanism by which smooth muscle cells switch to an osteogenic differentiation programme. Therefore, this review will describe the current concepts of pathological soft tissue mineralization, with a focus on the contribution of SIRT1 as a regulator of Wnt signaling and its targets, discussing SIRT1 as a potential target for manipulation and therapy.
血管钙化是一项重大的健康风险，与动脉粥样硬化、糖尿病和慢性肾病高度相关。血管钙化的发展是一个活跃且复杂的过程，与众多信号通路相关联，这些信号通路调节成骨作用的促进因子和抑制因子，在疾病状态下它们之间的平衡会失调。沉默信息调节因子1（SIRT1）是一种蛋白质脱乙酰酶，已知其在抑制血管壁内的氧化应激和炎症方面具有保护作用，已被证明可能是调节决定细胞命运的经典Wnt信号通路的关键因子。据报道，心血管疾病患者体内SIRT1受到抑制，这表明成骨因子的持续乙酰化可能促使其激活，进而导致钙化进展。有明确证据表明β-连环蛋白（β-Catenin）与升高的Runx2之间存在协同作用，且由于Wnt信号依赖于β-连环蛋白，因此需要进一步了解这些分子通路是如何汇聚和相互作用的，以便为平滑肌细胞转变为成骨分化程序的机制提供新的见解。因此，本综述将描述病理性软组织矿化的当前概念，重点关注SIRT1作为Wnt信号及其靶点的调节因子的作用，探讨SIRT1作为潜在的干预和治疗靶点。
