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HIV-1 matrix protein p17 promotes angiogenesis via chemokine receptors CXCR1 and CXCR2.

ABSTRACT: Vascular diseases supported by aberrant angiogenesis have increased incidence in HIV-1-infected patients. Several data suggest that endothelium dysfunction relies on action of HIV-1 proteins rather than on a direct effect of the virus itself. The HIV-1 matrix protein p17 is known to deregulate the biological activity of different immune cells. Recently, p17 was found to mimic IL-8 chemokine activity by binding to the IL-8 receptor CXCR1. Here we show that p17 binds with high affinity to CXCR2, a CXCR1-related receptor, and promotes the formation of capillary-like structures on human endothelial cells (ECs) by interacting with both CXCR1 and CXCR2 expressed on the EC surface. ERK signaling via Akt was defined as the pathway responsible for p17-induced tube formation. Ex vivo and in vivo experimental models confirmed the provasculogenic activity of p17, which was comparable to that induced by VEGF-A. The hypothesis of a major role for p17 in HIV-1-induced aberrant angiogenesis is enforced by the finding that p17 is detected, as a single protein, in blood vessels of HIV-1-patients and in particular in the nucleus of ECs. Localization of p17 in the nucleus of ECs was evidenced also in in vitro experiments, suggesting the internalization of exogenous p17 in ECs by mechanisms of receptor-mediated endocytosis. Recognizing p17 interaction with CXCR1 and CXCR2 as the key event in sustaining EC aberrant angiogenesis could help us to identify new treatment strategies in combating AIDS-related vascular diseases.

SUBMITTER: Caccuri F

PROVIDER: S-EPMC3437870 | biostudies-other | 2012 Sep

REPOSITORIES: biostudies-other

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HIV-1 matrix protein p17 promotes angiogenesis via chemokine receptors CXCR1 and CXCR2.

Caccuri Francesca F Giagulli Cinzia C Bugatti Antonella A Benetti Anna A Alessandri Giulio G Ribatti Domenico D Marsico Stefania S Apostoli Paola P Slevin Mark A MA Rusnati Marco M Guzman Carlos A CA Fiorentini Simona S Caruso Arnaldo A

Proceedings of the National Academy of Sciences of the United States of America 20120817 36

Vascular diseases supported by aberrant angiogenesis have increased incidence in HIV-1-infected patients. Several data suggest that endothelium dysfunction relies on action of HIV-1 proteins rather than on a direct effect of the virus itself. The HIV-1 matrix protein p17 is known to deregulate the biological activity of different immune cells. Recently, p17 was found to mimic IL-8 chemokine activity by binding to the IL-8 receptor CXCR1. Here we show that p17 binds with high affinity to CXCR2, a ...[more]

PMID: 22904195

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HIV-1 matrix protein p17 promotes angiogenesis via chemokine receptors CXCR1 and CXCR2.

Publications

HIV-1 matrix protein p17 promotes angiogenesis via chemokine receptors CXCR1 and CXCR2.

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