Copyright © 2005, European Society of Cardiology
Altered cardiac expression of peroxisome proliferator-activated receptor-isoforms in patients with hypertensive heart disease
aDivision of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, CIMA, Avda. Pío XII 55, 31008 Pamplona, Spain
bDivision of Cardiology, Donostia University Hospital, San Sebastián, Spain
cDivision of Haemodynamics, Guipuzcoa Polyclinics, San Sebastián, Spain
dDepartment of Cardiology and Cardiovascular Surgery, University Clinic, School of Medicine, University of Navarra, Pamplona, Spain
* Corresponding author. Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, CIMA, Avda. Pío XII 55, 31008 Pamplona, Spain. Tel.: +34 948194700x3000; fax: +34 948194716. Email address: jadimar{at}unav.es
Objective: To investigate whether cardiac expression of the nuclear peroxisome proliferator-activated receptor 
(PPAR) 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 PPAR isoforms (the native active and the truncated inhibitory) was analyzed by Western blot and reverse transcription polymerase chain reaction (RT–PCR), and two PPAR 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 protein was lower (p<0.05) in LVH and HF groups than in the HT group, truncated PPAR protein was overexpressed (p<0.001) in the HF group as compared with LVH and HT groups. The mRNA expression of native and truncated PPAR was similar in the three groups of hypertensives. In addition, a progressive decrease (p for trend<0.05) in the two PPAR target genes mRNA expression was observed among HT, LVH and HF groups. The amount of truncated PPAR protein correlates directly with cardiomyocytes apoptosis and inversely with cardiomyocytes density in patients with HHD. In addition, the expression of truncated PPAR 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 PPAR isoforms is altered in patients with HHD, namely in those developing HF. An excess of the truncated inhibitory isoform may be involved in hypertensive left ventricular failure and remodeling.
KEYWORDS Hypertension; Heart failure; Hypertrophy; Peroxisome proliferator-activated receptor ; Isoforms
1 The first two authors (María J. Goikoetxea and F. Javier Beaumont) contributed equally to this work.
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