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 (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.
Original language | English |
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Pages (from-to) | 552-560 |
Number of pages | 9 |
Journal | Cardiovascular Research |
Volume | 96 |
Issue number | 3 |
Early online date | 22 Aug 2012 |
DOIs | |
Publication status | Published - 1 Dec 2012 |
Keywords
- Hypertension
- brain
- blood vessels