Document Detail

Upregulation of junctional adhesion molecule-A is a putative prognostic marker of hypertension.
MedLine Citation:
PMID:  22918977     Owner:  NLM     Status:  MEDLINE    
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 (AT(1)) 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 AT(1) 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.
Haibo Xu; Elizabeth B Oliveira-Sales; Fiona McBride; Beihui Liu; James Hewinson; Marie Toward; Emma B Hendy; Delyth Graham; Anna F Dominiczak; Monica Giannotta; Hidefumi Waki; Raimondo Ascione; Julian F R Paton; Sergey Kasparov
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-22
Journal Detail:
Title:  Cardiovascular research     Volume:  96     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-19     Completed Date:  2013-04-25     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  552-60     Citation Subset:  IM    
School of Physiology and Pharmacology, Bristol Heart Institute, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
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MeSH Terms
Angiotensin II
Angiotensin II Type 1 Receptor Blockers / pharmacology
Antihypertensive Agents / therapeutic use
Arterial Pressure
Biological Markers / metabolism
Blood Vessels / drug effects,  metabolism*,  physiopathology
Case-Control Studies
Cell Adhesion Molecules / genetics,  metabolism*
Cell Line
Disease Models, Animal
Hydralazine / pharmacology
Hypertension / chemically induced,  drug therapy,  genetics,  metabolism*,  physiopathology
Hypertension, Renovascular / drug therapy,  etiology,  metabolism*,  physiopathology
Losartan / pharmacology
Morpholinos / metabolism
Prehypertension / chemically induced,  drug therapy,  genetics,  metabolism*,  physiopathology
RNA, Messenger / metabolism
Rats, Inbred SHR
Rats, Inbred WKY
Receptors, Cell Surface / genetics,  metabolism*
Time Factors
Vasodilator Agents / pharmacology
Grant Support
PG/06/085//British Heart Foundation; RG/07/006//British Heart Foundation
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Antihypertensive Agents; 0/Biological Markers; 0/Cell Adhesion Molecules; 0/F11R protein, human; 0/JAM-1 protein, rat; 0/Morpholinos; 0/RNA, Messenger; 0/Receptors, Cell Surface; 0/Vasodilator Agents; 11128-99-7/Angiotensin II; 114798-26-4/Losartan; 86-54-4/Hydralazine

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