Human miR-221/222 in Physiological and Atherosclerotic Vascular Remodeling.
Human miR-221/222 in Physiological and Atherosclerotic Vascular Remodeling.
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DOI：
10.1155/2015/354517
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发表时间：
2015
影响因子：
--
通讯作者：
Bobryshev YV
中科院分区：
文献类型：
--
作者：
Chistiakov DA;Sobenin IA;Orekhov AN;Bobryshev YV
miR-221/222簇通过对血管平滑肌细胞（VSMC）和内皮细胞（EC）的作用而在血管生物学中发挥关键作用。这些miRNAs有助于血管重塑，这是一种涉及血管细胞响应血管损伤的表型和行为变化的适应性过程。在动脉粥样硬化等增生性血管疾病中，病理性血管重塑起着重要作用。miR-221/222簇控制EC的发育和分化，但抑制其促血管生成活化、增殖和迁移。miR-221/222主要涉及维持内皮完整性和支持静止EC表型。miR-221/222的血管表达在致动脉粥样硬化的初始阶段上调，导致抑制EC的血管生成募集并增加内皮功能障碍和EC凋亡。相反，这些miRNA刺激VSMC并从VSMC“收缩”表型转换为与诱导增殖和运动相关的“合成”表型。在动脉粥样硬化血管中，miR-221/222驱动新生内膜形成。这两种miRNAs都参与了VSMC的致动脉粥样硬化钙化。在晚期斑块中，慢性炎症下调EC中的miR-221/222表达，这反过来可以激活病变内的新血管生成。此外，这两种miRNAs都可能通过影响非血管组织（如脂肪组织、肝脏和骨骼肌）中的脂肪和葡萄糖代谢而导致心血管病理学。
A cluster of miR-221/222 is a key player in vascular biology through exhibiting its effects on vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). These miRNAs contribute to vascular remodeling, an adaptive process involving phenotypic and behavioral changes in vascular cells in response to vascular injury. In proliferative vascular diseases such as atherosclerosis, pathological vascular remodeling plays a prominent role. The miR-221/222 cluster controls development and differentiation of ECs but inhibits their proangiogenic activation, proliferation, and migration. miR-221/222 are primarily implicated in maintaining endothelial integrity and supporting quiescent EC phenotype. Vascular expression of miR-221/222 is upregulated in initial atherogenic stages causing inhibition of angiogenic recruitment of ECs and increasing endothelial dysfunction and EC apoptosis. In contrast, these miRNAs stimulate VSMCs and switching from the VSMC “contractile” phenotype to the “synthetic” phenotype associated with induction of proliferation and motility. In atherosclerotic vessels, miR-221/222 drive neointima formation. Both miRNAs contribute to atherogenic calcification of VSMCs. In advanced plaques, chronic inflammation downregulates miR-221/222 expression in ECs that in turn could activate intralesion neoangiogenesis. In addition, both miRNAs could contribute to cardiovascular pathology through their effects on fat and glucose metabolism in nonvascular tissues such as adipose tissue, liver, and skeletal muscles.
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影响因子：
3.7
作者：
Cardinali B;Castellani L;Fasanaro P;Basso A;Alemà S;Martelli F;Falcone G
通讯作者：
Falcone G
影响因子：
64.8
作者：
Chendrimada, TP;Gregory, RI;Shiekhattar, R
通讯作者：
Shiekhattar, R
影响因子：
5.6
作者：
Auld, Corinth A.;Fernandes, Karishma M.;Morrison, Ron F.
通讯作者：
Morrison, Ron F.
影响因子：
20.3
作者：
Cheng, C;van Haperen, R;Krams, R
通讯作者：
Krams, R
影响因子：
4.8
作者：
Chen, Yun;Leal, Alejandro D.;Gorski, David H.
通讯作者：
Gorski, David H.