MPS 07-01 THE ROLE OF HISTONE ACETYLATION AND MMP EXPRESSION IN VASCULAR REMODELING OF RENAL ARTERIOLES IN DOCA-SALT HYPERTENSIVE MICE

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Abstract

Objective:

The role of salt intake in the development of hypertension is familiar, but the mechanism has not been revealed. Our previous report showed that the medial hypertrophy of renal arterioles induced by transient salt loading caused lasting renin elevation resulting in elevation of blood pressure in spontaneous hypertensive rat. The present study investigated the significance of epigenetic modulation of renal arterioles in the induction of medial hypertrophy after transient salt loading.

Design and Method:

Male 8 week old C57bl6 mice were implanted deoxycorticosterone acetate (DOCA) pellets and given drinking water containing 1% NaCl for 2 weeks to introduce salt-induced hypertension. Blood pressure was measured by tail-cuff method during and after transient salt loading. Histological examinations of the kidney were performed. Gene expressions in the whole kidney and renal arterioles were quantified using real time PCR and laser capture microdissection. To investigate the significance of histone acetylation, DOCA-salt mice were treated with histone acetyltransferase (HAT) inhibitor curcumin during salt loading.

Results:

Transient salt loading caused medial hypertrophy of renal arterioles and elevation in blood pressure during and even after salt loading. Real time PCR in the whole kidney revealed that the gene expressions of HATs such as CBP and p300 were elevated; and conversely those of histone deacetylases such as Sirts and HDACs were decreased during salt loading. Histone H3 and H4 acetylation in the promoter region of MMP-2 gene was enhanced during salt loading. MMP-2 and p300 in the renal arterioles were also increased during salt loading. Curcumin reduced the medial hypertrophy of renal arterioles and elevation in blood pressure partially.

Conclusions:

The lasting medial hypertrophy after transient salt loading was suggested to be caused by the increase of MMP-2 expression along with histone acetylation. Increased expressions of HATs and decreased expressions of HDACs were supposed to be involved in the enhancement of histone acetylation.

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