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


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.


CONCLUSIONS
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.
School of Physiology and Pharmacology,  Bristol Heart Institute, Medical Sciences Building, University of Bristol, Bristol BS8 1TD,  UK.
Haibo
H
Xu
Elizabeth B
EB
Oliveira-Sales
Fiona
F
McBride
Beihui
B
Liu
James
J
Hewinson
Marie
M
Toward
Emma B
EB
Hendy
Delyth
D
Graham
Anna F
AF
Dominiczak
Monica
M
Giannotta
Hidefumi
H
Waki
Raimondo
R
Ascione
Julian F R
JF
Paton
Sergey
S
Kasparov
D000804:Angiotensin II; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D062186:Arterial Pressure; D015415:Biomarkers / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004195:Disease Models, Animal; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006978:Hypertension, Renovascular / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D060172:Morpholinos / Q000378:metabolism; D058246:Prehypertension / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation; D014665:Vasodilator Agents / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D015415:Biomarkers; D015815:Cell Adhesion Molecules; C407243:F11R protein, human; C520495:F11r protein, rat; D060172:Morpholinos; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D014665:Vasodilator Agents; D000804:Angiotensin II; D006830:Hydralazine; D019808:Losartan