Background: Proliferation of the vasa vasorum has been implicated in the pathogenesis of atherosclerosis, and\nthe vasa vasorum is closely associated with resident stem cells within the vasculature. C-reactive protein (CRP)\nis positively correlated with cardiovascular disease risk, and our previous study demonstrated that it induces\ninflammatory reactions of perivascular adipose tissue by targeting adipocytes.\nMethods: Here we investigated whether CRP affected the proliferation and proangiogenic paracrine activity\nof adipose-derived stem cells (ADSCs), which may contribute to vasa vasorum angiogenesis.\nResults: We found that CRP did not affect ADSC apoptosis, cell cycle, or proliferation but did increase their\nmigration by activating the PI3K/Akt pathway. Our results demonstrated that CRP can upregulate vascular\nendothelial growth factor-A (VEGF-A) expression by activating hypoxia inducible factor-1�± (HIF-1�±) in ADSCs,\nwhich significantly increased tube formation on Matrigel and functional vessels in the Matrigel plug\nangiogenesis assay. The inhibition of CRP-activated phosphorylation of ERK and Akt can suppress CRPstimulated\nHIF-1�± activation and VEGF-A expression. CRP can also stimulate proteolytic activity of matrix\nmetalloproteinase-2 in ADSCs. Furthermore, CRP binds activating CD64 on ADSCs, rather than CD16/32.\nConclusion: Our findings implicate that CRP might play a role in vasa vasorum growth by activating the\nproangiogenic activity of ADSCs.
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