Nussenzweig Samuel C, Verma Subodh, Finkel Toren
From the Center for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (S.C.N, T.F.); and Division of Cardiac Surgery, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada (S.V.).
Circ Res. 2015 Jan 30;116(3):480-8. doi: 10.1161/CIRCRESAHA.116.303805.
There is increasing interest in the role of autophagic flux in maintaining normal vessel wall biology and a growing suspicion that autophagic dysregulation may be a common pathway through which vascular aging and associated pathologies develop. Within endothelial and smooth muscle cells, diverse but important triggers that range from oxidized lipids to β-amyloid seem to stimulate autophagosome formation potently. In addition, emerging evidence links autophagy to a wide array of vascular processes ranging from angiogenesis to calcification of the vessel wall. Alterations in autophagic flux are also increasingly being implicated in disease processes that include both atherosclerosis and pulmonary hypertension. Finally, recent insights point toward an important role of autophagy in the paracrine regulation of vasoactive substances from the endothelium. Here, we review the progress in understanding how autophagy can contribute to vascular biology and the emerging strategies to target this process for therapeutic benefit.
自噬通量在维持正常血管壁生物学功能中的作用正受到越来越多的关注,并且人们越来越怀疑自噬失调可能是血管衰老及相关病理发展的共同途径。在内皮细胞和平滑肌细胞中,从氧化脂质到β淀粉样蛋白等各种不同但重要的触发因素似乎能有力地刺激自噬体的形成。此外,新出现的证据将自噬与从血管生成到血管壁钙化等一系列广泛的血管过程联系起来。自噬通量的改变也越来越多地与包括动脉粥样硬化和肺动脉高压在内的疾病过程相关。最后,最近的研究表明自噬在内皮细胞旁分泌血管活性物质的调节中起着重要作用。在此,我们综述了在理解自噬如何影响血管生物学方面取得的进展,以及针对这一过程以获得治疗益处的新出现的策略。
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