Indexed on: 20 Sep '16Published on: 20 Sep '16Published in: Journal of hypertension
Left ventricular hypertrophy (LVH) is prevalent in chronic kidney disease (CKD) and a major cause of cardiovascular morbidity and mortality. Treatment of LVH in CKD is based on blood pressure control. The Kruppel like factor 15 (KLF15) is expressed in the heart and acts as a repressor of cardiac hypertrophy and fibrosis. The role of cardiac KLF15 in the development of LVH in rats with CKD secondary to subtotal nephrectomy (STNx) or the effects of ACE inhibition on KLF15 levels has not been addressed previously.Female Sprague Dawley rats underwent STNx and were treated for 4 weeks with either vehicle or the ACE inhibitor ramipril (oral 1mg/kg). Control rats received vehicle (all groups, n = 8/gp). Blood pressure and cardiac function were measured by catheterisation of the left ventricle.STNx rats were hypertensive (P < 0.05) with LVH and diastolic dysfunction, and had increased interstitial and perivascular fibrosis (all P < 0.05). STNx rats had significantly reduced cardiac KLF15 gene and protein expression (P < 0.05). In STNx (vs. STNx-vehicle), ramipril reduced blood pressure (P < 0.01), improved LVH and perivascular fibrosis (P < 0.01) and increased cardiac KLF15 protein (P < 0.05) but did not significantly reduce interstitial fibrosis.This is the first report that cardiac KLF15 is down regulated in LVH associated with CKD. ACE inhibition increased KLF15 and reduced LVH but it had no effect on interstitial fibrosis. Studies are now needed to investigate new approaches that lead to further increases in KLF15 and reduce the adverse effects of LVH in CKD.