Integrin beta3 regulates clonality and fate of smooth muscle-derived atherosclerotic plaque cells.
Integrin beta3 regulates clonality and fate of smooth muscle-derived atherosclerotic plaque cells.
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DOI：
10.1038/s41467-018-04447-7
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发表时间：
2018-05-25
影响因子：
16.6
通讯作者：
Greif DM
中科院分区：
文献类型：
--
作者：
Misra A;Feng Z;Chandran RR;Kabir I;Rotllan N;Aryal B;Sheikh AQ;Ding L;Qin L;Fernández-Hernando C;Tellides G;Greif DM
血管平滑肌细胞(SMC)在动脉粥样硬化形成中起着关键作用。然而，动脉粥样硬化斑块中预先存在的SMC的扩张和命运的调节机制仍然不清楚。我们在这里展示了多个SMC前体细胞在发育过程中混合形成主动脉。相反，在动脉粥样硬化形成过程中，单个SMC会产生最初包裹在动脉粥样硬化斑块帽子上的平滑肌源性细胞。随后，高增殖帽细胞侵入斑块核心，构成斑块细胞的大多数。SMC中整合素β3水平的降低可诱导Toll样受体4的表达，从而增强CD36水平和胆固醇诱导的转分化为巨噬细胞样表型。全球ITGB3缺失或移植ITGB3(−/−)骨髓导致多个预先存在的SMC重新聚集到斑块中。ITGB3沉默的巨噬细胞条件培养液可促进SMC的增殖和迁移。综上所述，我们的研究结果表明，在SMC和骨髓来源的细胞中，SMC在动脉粥样硬化形成中的作用是由整合素β3介导的途径调节的。平滑肌细胞(SMC)侵袭动脉粥样硬化病变并扩张，促进斑块的发展。在这里，Misra等人。研究表明，SMC来源的斑块细胞来自单个SMC，SMC和巨噬细胞中的整合素β3调控斑块形成过程中SMC的命运、扩张和迁移。
Smooth muscle cells (SMCs) play a key role in atherogenesis. However, mechanisms regulating expansion and fate of pre-existing SMCs in atherosclerotic plaques remain poorly defined. Here we show that multiple SMC progenitors mix to form the aorta during development. In contrast, during atherogenesis, a single SMC gives rise to the smooth muscle-derived cells that initially coat the cap of atherosclerotic plaques. Subsequently, highly proliferative cap cells invade the plaque core, comprising the majority of plaque cells. Reduction of integrin β3 (Itgb3) levels in SMCs induces toll-like receptor 4 expression and thereby enhances Cd36 levels and cholesterol-induced transdifferentiation to a macrophage-like phenotype. Global Itgb3 deletion or transplantation of Itgb3(−/−) bone marrow results in recruitment of multiple pre-existing SMCs into plaques. Conditioned medium from Itgb3-silenced macrophages enhances SMC proliferation and migration. Together, our results suggest SMC contribution to atherogenesis is regulated by integrin β3-mediated pathways in both SMCs and bone marrow-derived cells. Smooth muscle cells (SMCs) invade atherosclerotic lesions and expand, contributing to plaque progression. Here Misra et al. show that SMC-derived plaque cells come from a single SMC and integrin β3 in SMCs and macrophages regulate the fate, expansion and migration of SMCs during plaque formation.
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影响因子：
15.9
作者：
Hodivala-Dilke, KM;McHugh, KP;Hynes, RO
通讯作者：
Hynes, RO
影响因子：
4.8
作者：
Rotllan, Noemi;Chamorro-Jorganes, Aranzazu;Fernandez-Hernando, Carlos
通讯作者：
Fernandez-Hernando, Carlos
DOI：
10.1073/pnas.70.6.1753
发表时间：
1973-01-01
影响因子：
11.1
作者：
BENDITT, EP;BENDITT, JM
通讯作者：
BENDITT, JM
影响因子：
8
作者：
Jacobsen, Kevin;Lund, Marie Bek;Bentzon, Jacob Fog
通讯作者：
Bentzon, Jacob Fog
DOI：
10.1016/j.biocel.2010.02.009
发表时间：
2010-06
影响因子：
4
作者：
Panchatcharam, Manikandan;Miriyala, Sumitra;Yang, Fanmuyi;Leitges, Michael;Chrzanowska-Wodnicka, Magdalena;Quilliam, Lawrence A.;Anaya, Paul;Morris, Andrew J.;Smyth, Susan S.
通讯作者：
Smyth, Susan S.