Deletion of MicroRNA-21 Impairs Neovascularization Following Limb Ischemia: From Bedside to Bench.
Deletion of MicroRNA-21 Impairs Neovascularization Following Limb Ischemia: From Bedside to Bench.
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DOI：
10.3389/fcvm.2022.826478
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发表时间：
2022
影响因子：
3.6
通讯作者：
中科院分区：
文献类型：
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作者：
随着发病率的增加，由动脉粥样硬化引起的外周动脉疾病(PAD)已成为除冠状动脉疾病之外的一种新的公共健康威胁，涉及血管内皮细胞异常增殖和血管生成。血管重塑的程度受所述过程的影响。MicroRNA-21(miR-21)在包括血管生成在内的细胞功能中发挥重要作用。然而，miR-21对内皮细胞缺氧反应的影响在很大程度上是未知的。我们利用野生型C57BL/6J和miR-21-/-小鼠，比较了它们对后肢缺氧/缺血反应的血管生成能力。在体外研究中，我们进一步研究了miR-21的过表达是否减轻了缺氧诱导的细胞凋亡和受损的血管生成。此外，我们前瞻性地收集了肢体缺血患者的血清，并跟踪了包括主要不良肢体事件(男性)在内的临床信息。激光多普勒血流成像和CD31染色显示，与miR-21-/-小鼠相比，野生型小鼠在28天的后肢缺氧/缺血手术后表现出明显更高的血管生成能力和更少的细胞凋亡。在我们的体外研究中，在缺氧24小时后，用miR-21抑制剂处理的细胞的增殖、迁移和管状形成明显受损，但被miR-21模拟物挽救。机制上，miR-21通过抑制PTEN/PI3K/AKT，促进缺氧后内皮细胞血管生成，抑制细胞凋亡。在肢体缺血患者中，循环miR-21的高表达与随后的男性较少相关。总的来说，miR-21可能是一个与内源性血管生成能力相关的生物标志物，并反映患者随后的男性。此外，取消miR-21会损害肢体缺血后的血管生成并促进细胞凋亡。MiR-21的临床应用尚需进一步研究。
With an increasing prevalence, peripheral arterial disease (PAD), cause by atherosclerosis is a new threat to public health beyond coronary artery disease and involves aberrant vascular endothelial cell proliferation and angiogenesis. The degree of vascular remodeling is influenced by the processes described. MicroRNA-21 (miR-21) has been found to play a critical role in cellular functions, including angiogenesis. Nevertheless, the effect of miR-21 on endothelial cells in response to hypoxia is largely unknown. Using wild-type C57BL/6J and miR-21–/– mice, we compared the capability of angiogenesis in response to hindlimb hypoxic/ischemia. In an in vitro study, we further studied whether overexpression of miR-21 mitigates hypoxia-induced apoptosis and impaired angiogenesis. Also, we prospectively collected the sera of patients with limb ischemia and followed the clinical information, including major adverse limb events (MALEs). Using laser Doppler perfusion imaging and CD31 staining, compared with miR-21–/– mice, wild-type mice expressed a significantly higher capability of angiogenesis and less apoptosis following 28 days of hindlimb hypoxic/ischemic surgery. In our in vitro study, after 24 h of hypoxia, proliferation, migration, and tube formation were significantly impaired in cells treated with the miR-21 inhibitor but rescued by the miR-21 mimic. Mechanistically, by suppressing PTEN/PI3K/AKT, miR-21 promoted angiogenesis and suppressed apoptosis in endothelial cells post hypoxia. In patients with limb ischemia, the high expression of circulating miR-21 was associated with less subsequent MALE. Collectively, miR-21 could be a biomarker associated with the endogenous ability of angiogenesis and reflect subsequent MALE in patients. Additionally, abolishing miR-21 impairs angiogenesis and promotes apoptosis post limb ischemia. Further studies are required to elucidate the clinical applications of miR-21.
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影响因子：
13.8
作者：
Semenza GL
通讯作者：
Semenza GL
影响因子：
3.4
作者：
Lu, Jian-Min;Zhang, Zhen-Zhen;Qin, Xiu-Hong
通讯作者：
Qin, Xiu-Hong
miR-21 通过靶向 FASLG 诱导内皮祖细胞增殖和血管生成，是深静脉血栓形成的潜在预后标志物
影响因子：
7.4
作者：
Du, Xiaolong;Hong, Lei;Li, Xiaoqiang
通讯作者：
Li, Xiaoqiang
影响因子：
158.5
作者：
Bonaca, Marc P.;Bauersachs, Rupert M.;Hiatt, William R.
通讯作者：
Hiatt, William R.
DOI：
10.31557/apjcp.2020.21.10.2817
发表时间：
2020-10-01
期刊：
Asian Pacific journal of cancer prevention : APJCP
影响因子：
--
作者：
Chang WT;Huang TL;Chen ZC;Feng YH
通讯作者：
Feng YH