Upregulation of junctional adhesion molecule-A is a putative prognostic marker of hypertension

Xu, H. et al. (2012) Upregulation of junctional adhesion molecule-A is a putative prognostic marker of hypertension. Cardiovascular Research, 96(3), pp. 552-560. (doi: 10.1093/cvr/cvs273) (PMID:22918977) (PMCID:PMC3500047)

Abstract

Aims Establishing biochemical markers of pre-hypertension and early hypertension could help earlier diagnostics and therapeutic intervention. We assess dynamics of junctional adhesion molecule-A (JAM-A) expression in rat models of hypertension and test whether JAM-A expression could be driven by angiotensin (ANG) II and whether JAM-A contributes to the progression of hypertension. We also compare JAM-A expression in normo- and hypertensive humans. Methods and results In pre-hypertensive and spontaneously hypertensive rats (SHRs), JAM-A protein was overexpressed in the brainstem microvasculature, lung, liver, kidney, spleen, and heart. JAM-A upregulation at early and late stages was even greater in the stroke-prone SHR. However, JAM-A was not upregulated in leucocytes and platelets of SHRs. In Goldblatt 2K-1C hypertensive rats, JAM-A expression was augmented before any increase in blood pressure, and similarly JAM-A upregulation preceded hypertension caused by peripheral and central ANG II infusions. In SHRs, ANG II type 1 (AT1) receptor antagonism reduced JAM-A expression, but the vasodilator hydralazine did not. Body-wide downregulation of JAM-A with Vivo-morpholinos in juvenile SHRs delayed the progression of hypertension. In the human saphenous vein, JAM-A mRNA was elevated in hypertensive patients with untreated hypertension compared with normotensive patients but reduced in patients treated with renin–angiotensin system antagonists. Conclusion Body-wide upregulation of JAM-A in genetic and induced models of hypertension in the rat precedes the stable elevation of arterial pressure. JAM-A upregulation may be triggered by AT1 receptor-mediated signalling. An association of JAM-A with hypertension and sensitivity to blockers of ANG II signalling were also evident in humans. We suggest a prognostic and possibly a pathogenic role of JAM-A in arterial hypertension.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Graham, Dr Delyth and Dominiczak, Professor Anna
• Authors: Xu, H., Oliveira-Sales, E.B., McBride, F., Liu, B., Hewinson, J., Toward, M., Hendy, E.B., Graham, D., Dominiczak, A.F., Giannotta, M., Waki, H., Ascione, R., Paton, J.F.R., and Kasparov, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Cardiovascular Research
• Publisher: Oxford University Press
• ISSN: 0008-6363
• Published Online: 22 August 2012
• Copyright Holders: Copyright © 2012 The Authors
• First Published: First published in Cardiovascular Research 96(3):552-560
• Publisher Policy: Reproduced under a Creative Commons License