Adipocyte-derived factors regulate vascular smooth muscle cells through mineralocorticoid and glucocorticoid receptors

Nguyen Dinh Cat, A., Briones, A.M., Callera, G.E., Yogi, A., He, Y., Montezano, A.C. and Touyz, R.M. (2011) Adipocyte-derived factors regulate vascular smooth muscle cells through mineralocorticoid and glucocorticoid receptors. Hypertension, 58(3), pp. 479-488. (doi:10.1161/HYPERTENSIONAHA.110.168872)

Full text not currently available from Enlighten.

Publisher's URL: http://dx.doi.org/10.1161/HYPERTENSIONAHA.110.168872

Abstract

Adipose tissue influences vascular function through adipocyte-derived factors, including components of the renin-angiotensin-aldosterone system. Molecular mechanisms underlying these phenomena are elusive. We investigated the role of adipocyte-derived factors on mitogen-activated protein kinases (MAPKs), proinflammatory status, apoptosis, and mitogenic signaling in vascular smooth muscle cells (VSMCs) and questioned whether these effects involve mineralocorticoid receptor (MR), glucocorticoid receptor (GR), and angiotensin II type 1 receptor (AT1R). Cultured mouse VSMCs were exposed to adipocyte-conditioned medium (ACM) from differentiated 3T3-L1 adipocytes. ACM induced phosphorylation of stress-activated protein kinase/c-Jun N-terminal kinase, p38MAPK, and extracellular signal–regulated kinase 1/2 and increased expression of proinflammatory and proliferative markers in VSMCs. Eplerenone (MR antagonist), mifepristone (GR antagonist), and candesartan (AT1R antagonist) inhibited ACM-induced effects on extracellular signal–regulated kinase 1/2, p38MAPK, and proliferating cell nuclear antigen, without influencing apoptosis (Bax, Bcl, and caspase 3). Stress-activated protein kinase/c-Jun N-terminal kinase phosphorylation was inhibited by mifepristone and candesartan but not by eplerenone. ACM-induced increase of fibronectin, vascular cell adhesion molecule 1, and plasminogen activator inhibitor 1 expression was blocked by MR and AT1R antagonism but not by GR inhibition. ACM has no effect on GR, MR, and AT1R expression. Our data show that adipocyte-derived factors influence MAPK signaling, leading to VSMC proinflammatory and profibrotic responses through distinct pathways. Although ACM stimulates p38MAPK and extracellular signal–regulated kinase 1/2 phosphorylation through MR, GR, and AT1R, activation of stress-activated protein kinase/c-Jun N-terminal kinase involves GR and AT1R. These findings suggest that adipocyte-derived factors regulate VSMC function through specific MAPKs linked to MR, GR, and AT1R, a posttranslational phenomenon, because ACM did not influence receptor expression. Such cross-talk between adipocytes and VSMCs may provide a potential molecular mechanism linking renin-angiotensin-aldosterone system, adipocytes, and vascular function.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Montezano, Dr Augusto and Touyz, Professor Rhian
Authors: Nguyen Dinh Cat, A., Briones, A.M., Callera, G.E., Yogi, A., He, Y., Montezano, A.C., and Touyz, R.M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Hypertension
ISSN:0194-911X
ISSN (Online):1524-4563
Published Online:25 July 2011

University Staff: Request a correction | Enlighten Editors: Update this record