C-reactive protein can upregulate VEGF expression to promote ADSC-induced angiogenesis by activating HIF-1α via CD64/PI3k/Akt and MAPK/ERK signaling pathways.
C-reactive protein can upregulate VEGF expression to promote ADSC-induced angiogenesis by activating HIF-1α via CD64/PI3k/Akt and MAPK/ERK signaling pathways.
复制标题
C反应蛋白可通过CD64/PI3k/Akt和MAPK/ERK信号通路激活HIF-1α，上调VEGF表达，促进ADSC诱导的血管生成
DOI：
10.1186/s13287-016-0377-1
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发表时间：
2016-08-16
影响因子：
7.5
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Chen J;Gu Z;Wu M;Yang Y;Zhang J;Ou J;Zuo Z;Wang J;Chen Y
血管的增殖与动脉粥样硬化的发病机制有关，并且血管与脉管系统内的常驻干细胞密切相关。C-反应蛋白（CRP）与心血管疾病风险呈正相关，我们以前的研究表明，它通过靶向脂肪细胞诱导血管周围脂肪组织的炎症反应。在这里，我们研究了CRP是否影响脂肪干细胞（ADSC）的增殖和促血管生成的旁分泌活性，这可能有助于血管新生。我们发现CRP不影响ADSC的凋亡、细胞周期或增殖，但通过激活PI 3 K/Akt通路增加其迁移。我们的研究结果表明，CRP可以通过激活ADSC中的缺氧诱导因子-1 α（HIF-1α）来上调血管内皮生长因子-A（VEGF-A）的表达，这在Matrigel栓塞血管生成试验中显著增加Matrigel上的管形成和功能性血管。抑制CRP激活的ERK和Akt的磷酸化可以抑制CRP刺激的HIF-1α激活和VEGF-A表达。CRP还可以刺激ADSC中基质金属蛋白酶-2的蛋白水解活性。此外，CRP结合ADSC上的活化CD 64，而不是CD 16/32。我们的研究结果表明，CRP可能通过激活ADSC的促血管生成活性在血管生长中发挥作用。本文的在线版本（doi：10.1186/s13287-016-0377-1）包含补充材料，可供授权用户使用。
Proliferation of the vasa vasorum has been implicated in the pathogenesis of atherosclerosis, and the vasa vasorum is closely associated with resident stem cells within the vasculature. C-reactive protein (CRP) is positively correlated with cardiovascular disease risk, and our previous study demonstrated that it induces inflammatory reactions of perivascular adipose tissue by targeting adipocytes. Here we investigated whether CRP affected the proliferation and proangiogenic paracrine activity of adipose-derived stem cells (ADSCs), which may contribute to vasa vasorum angiogenesis. We found that CRP did not affect ADSC apoptosis, cell cycle, or proliferation but did increase their migration by activating the PI3K/Akt pathway. Our results demonstrated that CRP can upregulate vascular endothelial growth factor-A (VEGF-A) expression by activating hypoxia inducible factor-1α (HIF-1α) in ADSCs, which significantly increased tube formation on Matrigel and functional vessels in the Matrigel plug angiogenesis assay. The inhibition of CRP-activated phosphorylation of ERK and Akt can suppress CRP-stimulated HIF-1α activation and VEGF-A expression. CRP can also stimulate proteolytic activity of matrix metalloproteinase-2 in ADSCs. Furthermore, CRP binds activating CD64 on ADSCs, rather than CD16/32. Our findings implicate that CRP might play a role in vasa vasorum growth by activating the proangiogenic activity of ADSCs. The online version of this article (doi:10.1186/s13287-016-0377-1) contains supplementary material, which is available to authorized users.