Abstract

Adiponectin (Ad) is an insulin-sensitizing adipocytokine with anti-inflammatory and vasoprotective properties. Cleavage of native full-length Ad (fAd) by elastases from activated monocytes generates globular Ad (gAd). Increased gAd levels are observed in the proximity of atherosclerotic lesions, but the physiological meaning of this proteolytic Ad fragment in the cardiovascular system is controversial. We compared molecular and biological properties of fAd and gAd in human aortic endothelial cells (HAEC). In control HAEC, both fAd and gAd acutely stimulated nitric oxide (NO) production by AMPK-dependent pathways. With respect to fAd, gAd more efficiently increased activation of NF-kB signaling pathways resulting in cyclo-oxygenase 2 (COX-2) overexpression and COX-2-dependent prostacyclin 2 (PGI2) release. In contrast with fAd, gAd also increased p38MAPK phosphorylation and VCAM-1 expression, ultimately enhancing adhesion of monocytes to endothelial cells. In HAEC lacking AdipoR1 (by siRNA), both activation of NF-kB as well as COX-2 overexpression by gAd were abrogated. Conversely, gAd-mediated p38MAPK activation and VCAM-1 expression were unaffected, and monocyte adhesion greatly enhanced. In HAEC lacking COX-2 (by siRNA), reduced levels of PGI2 further increased gAd-dependent monocyte adhesion. Our findings suggest that biological activities of fAd and gAd in endothelium do not completely overlap, with gAd possessing both AdipoR1- dependent ability to stimulate COX-2 expression and AdipoR1-independent effects related to expression of VCAM-1 and adhesion of monocytes to endothelium.

Autore Pugliese

• Nacci Carmela , Montagnani Monica

Tutti gli autori

• NACCI C.;MONTAGNANI M.

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2011

ISSN

0193-1849

ISBN

Non Disponibile

Numero di citazioni Wos

25

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

34

Ultimo Aggiornamento Citazioni

Non Disponibile

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile