Multiple functions of autophagy in vascular calcification.
Multiple functions of autophagy in vascular calcification.
复制标题
自噬在血管钙化中的多种功能
DOI：
10.1186/s13578-021-00639-9
复制
发表时间：
2021-08-16
影响因子：
7.5
通讯作者：
Cao HL
中科院分区：
文献类型：
--
作者：
Zhou X;Xu SN;Yuan ST;Lei X;Sun X;Xing L;Li HJ;He CX;Qin W;Zhao D;Li PQ;Moharomd E;Xu X;Cao HL
背景血管钙化与动脉粥样硬化、慢性肾脏病、糖尿病、高血压、衰老等心血管疾病密切相关。血管钙化程度与不良临床事件和心血管全因死亡率密切相关。自噬在血管钙化中的作用是复杂的，有许多机械unknowns.MethodsIn this review，我们分析了目前已知的机制，自噬在血管钙化和讨论的理论优势，有针对性的自噬作为一种干预对vascular calcium.ResultsHere，我们总结了血管钙化和自噬在动物模型和人类心血管疾病之间的功能联系。首先，自噬可以通过抑制与ANCR、ERα、β-catenin、HIF-1a/PDK 4、p62、miR-30 b、BECN 1、mTOR、SOX 9、GHSR/ERK和AMPK信号通路相关的VSMC的成骨分化来减少钙化。相反，自噬可以诱导成骨细胞分化和钙化，如CREB介导的，弹性蛋白的降解，以及lncRNA H19和DUSP 5介导的ERK信号传导。其次，自噬还通过AMPK/mTOR/ULK 1、Wnt/β-catenin和GAS 6/AXL合成将凋亡与血管钙化联系起来，因为凋亡细胞成为钙-磷酸盐晶体沉积的病灶。线粒体自噬的失败可以激活Drp 1，BNIP 3和NR 4A 1/DNA-PKcs/p53介导的内在凋亡途径，这些途径与血管钙化的形成密切相关。此外，自噬还通过调节血管钙化在骨生成中发挥作用，血管钙化反过来又调节与骨发育相关的蛋白质的表达，如骨钙素、骨粘连蛋白等，并受mTOR、EphrinB 2和RhoA的调节。此外，自噬还促进维生素K2诱导的MC 3 T3 E1成骨细胞分化和FGFR 4/FGF 18-和JNK/复合物VPS 34-beclin-1-相关的骨矿化via vascular calcium.ConclusionThe自噬和血管钙化之间的相互作用是复杂的，其相互作用受疾病过程，解剖位置和周围微环境的影响。存在的细胞损伤中的自噬激活被认为是保护性的，而正常细胞中有缺陷的自噬导致凋亡激活。识别和维持细胞在这两种状态之间的微妙界限可能是减少血管钙化的关键，其中可以开发自噬相关的临床策略。
BackgroundVascular calcification is a closely linked to cardiovascular diseases, such as atherosclerosis, chronic kidney disease, diabetes, hypertension and aging. The extent of vascular calcification is closely correlate with adverse clinical events and cardiovascular all-cause mortality. The role of autophagy in vascular calcification is complex with many mechanistic unknowns.MethodsIn this review, we analyze the current known mechanisms of autophagy in vascular calcification and discuss the theoretical advantages of targeting autophagy as an intervention against vascular calcification.ResultsHere we summarize the functional link between vascular calcification and autophagy in both animal models of and human cardiovascular disease. Firstly, autophagy can reduce calcification by inhibiting the osteogenic differentiation of VSMCs related to ANCR, ERα, β-catenin, HIF-1a/PDK4, p62, miR-30b, BECN1, mTOR, SOX9, GHSR/ERK, and AMPK signaling. Conversely, autophagy can induce osteoblast differentiation and calcification as mediated by CREB, degradation of elastin, and lncRNA H19 and DUSP5 mediated ERK signaling. Secondly, autophagy also links apoptosis and vascular calcification through AMPK/mTOR/ULK1, Wnt/β-catenin and GAS6/AXL synthesis, as apoptotic cells become the nidus for calcium-phosphate crystal deposition. The failure of mitophagy can activate Drp1, BNIP3, and NR4A1/DNA‑PKcs/p53 mediated intrinsic apoptotic pathways, which have been closely linked to the formation of vascular calcification. Additionally, autophagy also plays a role in osteogenesis by regulating vascular calcification, which in turn regulates expression of proteins related to bone development, such as osteocalcin, osteonectin, etc. and regulated by mTOR, EphrinB2 and RhoA. Furthermore, autophagy also promotes vitamin K2-induced MC3T3 E1 osteoblast differentiation and FGFR4/FGF18- and JNK/complex VPS34–beclin-1-related bone mineralization via vascular calcification.ConclusionThe interaction between autophagy and vascular calcification are complicated, with their interaction affected by the disease process, anatomical location, and the surrounding microenvironment. Autophagy activation in existent cellular damage is considered protective, while defective autophagy in normal cells result in apoptotic activation. Identifying and maintaining cells at the delicate line between these two states may hold the key to reducing vascular calcification, in which autophagy associated clinical strategy could be developed.
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影响因子：
4.8
作者：
Colella, Barbara;Faienza, Fiorella;Di Bartolomeo, Sabrina
通讯作者：
Di Bartolomeo, Sabrina
影响因子：
5.6
作者：
Ciceri, Paola;Falleni, Monica;Cozzolino, Mario
通讯作者：
Cozzolino, Mario
影响因子：
10.8
作者：
Durham AL;Speer MY;Scatena M;Giachelli CM;Shanahan CM
通讯作者：
Shanahan CM
影响因子：
--
作者：
Ávalos Y;Canales J;Bravo-Sagua R;Criollo A;Lavandero S;Quest AF
通讯作者：
Quest AF
影响因子：
20.1
作者：
Abdellatif, Mahmoud;Sedej, Simon;Kroemer, Guido
通讯作者：
Kroemer, Guido