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

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, test whether JAM-A expression could be driven by angiotensin 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 hypertensive spontaneously hypertensive rats (SHR), JAM-A protein was overexpressed in brainstem micro-vasculature, lung, liver, kidney, spleen and heart. JAM-A upregulation at early and late stages was even greater in the stroke prone SHR (SHRSP). However, JAM-A was not upregulated in leukocytes and platelets of SHR. 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 angiotensin-II infusions. In SHR, AT1 receptor antagonism reduced JAM-A expression, but the vasodilator hydralazine did not. Body-wide downregulation of JAM-A with Vivo-morpholinos in juvenile SHR delayed the progression of hypertension. In human saphenous vein, JAM-A mRNA was elevated in hypertensive patients with untreated hypertension compared to 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 AT1 receptor-mediated signaling. An association of JAM-A with hypertension and sensitivity to blockers of angiotensin II signalling were also evident in humans. We suggest a prognostic and possibly a pathogenic role of JAM-A in arterial hypertension.