Altered cardiac expression of peroxisome proliferator-activated receptor-isoforms in patients with hypertensive heart disease

Objective: To investigate whether cardiac expression of the nuclear peroxisome prolifierator-activated receptor a (PPAR alpha) is altered in patients with hypertensive heart disease (HHD). Methods: We studied endomyocardial septal biopsies from 24 patients with essential hypertension divided into three groups: 6 without left ventricular hypertrophy (LVH) (HT group), 10 with LVH (LVH group), and 8 with LVH and heart failure (HF) (HF group). The expression of two PPARa isoforms (the native active and the truncated inhibitory) was analyzed by Western blot and reverse transcription polymerase chain reaction (RT-PCR), and two PPARa target genes were evaluated by RT-PCR. Histomorphological -features were evaluated in a second myocardial sample from LVH and HF groups. Results: Whereas the expression of native PPAR alpha protein was lower (p < 0.05) in LVH and HF groups than in the HT group, truncated PPAR alpha protein was overexpressed (p < 0.001) in the HF group as compared with LVH and HT groups. The mRNA expression of native and truncated PPARa was similar in the three groups of hypertensives. In addition, a progressive decrease (p for trend < 0.05) in the two PPARoL target genes mRNA expression was observed among HT, LVH and HF groups. The amount of truncated PPARoL protein correlates directly with cardiomyocytes apoptosis and inversely with cardiomyocytes density in patients with HHD. In addition, the expression of truncated PPAR alpha protein was directly correlated with left ventricular volumes, and inversely with ejection fraction in all hypertensives. Conclusions: These findings suggest that post-transcriptional regulation of PPARa isoforms is altered in patients with HHD, namely in those developing HE An excess of the truncated inhibitory isoform may be involved in hypertensive left ventricular failure and remodeling. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.