Paradoxical effects of osteoprotegerin on vascular function: inhibiting inflammation while promoting oxidative stress?
Paradoxical effects of osteoprotegerin on vascular function: inhibiting inflammation while promoting oxidative stress?
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骨保护素对血管功能的副作用：抑制炎症同时促进氧化应激？
DOI：
10.1042/cs20211096
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发表时间：
2022-03-18
期刊：
影响因子：
--
通讯作者：
Abe JI
中科院分区：
文献类型：
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作者：
Le NT;Olmsted-Davis EA;Abe JI
骨保护素（OPG），也称为破骨细胞生成抑制因子或肿瘤坏死因子受体超家族成员11B，是众所周知的骨重建的调节剂。OPG在心血管疾病中的作用已被提出，但其分子机制尚不清楚。在本研究中，Alves-Lopes等人（Clin. Sci.（伦敦）（2021）135（20）：https：//doi.org/10.1042/CS20210643）报道了syndecan-1（SDC-1，也称为CD 138）（内皮糖萼的表面蛋白部分）在OPG诱导的血管功能障碍中的关键作用。作者发现，在内皮细胞（EC）中，OPG通过SDC-1增加eNOS Thr 495磷酸化，从而抑制eNOS活性。此外，OPG-SDC-1相互作用通过NOX 1/4活化增加活性氧（ROS）的产生。eNOS活性的降低和ROS的产生都抑制了NO的产生，损害了EC的功能。在血管平滑肌细胞（VSMC）中，OPG-SDC-1相互作用通过NOX 1/4激活增加ROS产生，随后增加MLC磷酸化介导的Rho激酶-MYPT 1调节，导致血管收缩增加。利用导丝肌电描记术和机制研究，作者很好地提供了SDC-1在OPG诱导的血管功能障碍中起关键作用的证据。如上所述，OPG在心血管系统中的分子机制和作用是复杂的，有些混乱。本文就OPG介导的心血管系统信号通路作一综述。
Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor or tumor necrosis factor receptor superfamily member 11B, is well known as a modulator of bone remodeling. The contribution of OPG to cardiovascular disease (CVD) has been suggested, but its molecular mechanism is complex and remains unclear. In the present study, Alves-Lopes et al. (Clin. Sci. (Lond.) (2021) 135(20): https://doi.org/10.1042/CS20210643) reported the critical role of syndecan-1 (SDC-1, also known as CD138), a surface protein part of the endothelial glycocalyx, in OPG-induced vascular dysfunction. The authors found that in endothelial cells (ECs), through SDC-1, OPG increased eNOS Thr495 phosphorylation, thereby inhibiting eNOS activity. Furthermore, the OPG–SDC-1 interaction increased reactive oxygen species (ROS) production through NOX1/4 activation. Both the reduced eNOS activity and induced ROS production inhibited NO production and impaired EC function. In vascular smooth muscle cells (VSMCs), the OPG–SDC-1 interaction increased ROS production through NOX1/4 activation, subsequently increased MLC phosphorylation-mediated Rho kinase-MYPT1 regulation, leading to increased vascular contraction. Ultilizing wire myography and mechanistic studies, the authors nicely provide the evidence that SDC-1 plays a crucial role in OPG-induced vascular dysfunction. As we mentioned above, the molecular mechanism and roles of OPG in cardiovascular system are complex and somewhat confusing. In this commentary, we briefly summarize the OPG-mediated signaling pathways in cardiovascular system.