Direct reciprocal effects of resistin and adiponectin on vascular endothelial cells: a new insight into adipocytokine–endothelial cell interactions

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Abstract

Resistin is an adipocytokine which plays a role in the development of insulin resistance. In this study, we investigated the direct effect of resistin on vascular endothelial cells. Resistin induced the expression of adhesion molecules such as VCAM-1 and ICAM-1, and long pentraxin 3, a marker of inflammation. The induction of VCAM-1 by resistin was inhibited partially by pitavastatin. Moreover, the induction of VCAM-1 and ICAM-1 by resistin was inhibited by adiponectin, an adipocytokine that improves insulin resistance. Taken together, these results suggest that the balance in the concentrations of adipocytokines such as resistin and adiponectin determines the inflammation status of vasculature, and in turn the progress of atherosclerosis.

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Materials and methods

Materials. Human recombinant resistin and mouse recombinant globular domain of adiponectin/Acrp30 were purchased from WAKO (Japan). Pitavastatin was kindly provided by Kowa (Japan).

Cell culture. Human aortic endothelial cells (HAECs, purchased from Bio-Whittaker) were cultured in endothelial cell growth medium-2 (EGM-2, Bio-Whittaker) at 37 °C in a humidified atmosphere of 5% CO2. Bovine aortic endothelial cells (BAECs, purchased from Bio-Whittaker) were cultured in Dulbecco’s modified Eagle’s

Resistin induces expression of adhesion molecules and pentraxin 3 in HAECs

To determine whether resistin directly affects vascular endothelial cell functions, we stimulated HAECs with human recombinant resistin and examined gene expression of adhesion molecules and of the inflammatory marker pentraxin 3 (PTX3), which shares high homology with C-reactive protein (CRP). Northern blot analysis revealed that resistin (30 nM) increased VCAM-1, ICAM-1, and PTX3 mRNA expression by 2 h, reaching a maximum at 4 or 8 h after resistin stimulation in HAECs (Fig. 1A). Resistin

Discussion

In this study, we have demonstrated that resistin induced mRNA expression of adhesion molecules and PTX3 in HAECs. Induction of VCAM-1 and ICAM-1 was confirmed also at protein level. Interestingly, pitavastatin partially prevented VCAM-1 induction by resistin. More importantly, adiponectin dramatically inhibited VCAM-1 induction by resistin in HAECs.

While we were preparing this manuscript, Verma et al. [10] also reported that resistin upregulated VCAM-1, endothelin-1, and monocyte

Acknowledgements

We thank Chie Fujinami for technical assistance. This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Japan.

References (22)

  • C.M. Steppan et al.

    The hormone resistin links obesity to diabetes

    Nature

    (2001)
  • Cited by (0)

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