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 proliferator-activated receptor alpha (PPARalpha) 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 PPARalpha isoforms (the native active and the truncated inhibitory) was analyzed by Western blot and reverse transcription polymerase chain reaction (RT-PCR), and two PPARalpha 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 PPARalpha protein was lower (p<0.05) in LVH and HF groups than in the HT group, truncated PPARalpha protein was overexpressed (p<0.001) in the HF group as compared with LVH and HT groups. The mRNA expression of native and truncated PPARalpha was similar in the three groups of hypertensives. In addition, a progressive decrease (p for trend<0.05) in the two PPARalpha target genes mRNA expression was observed among HT, LVH and HF groups. The amount of truncated PPARalpha protein correlates directly with cardiomyocytes apoptosis and inversely with cardiomyocytes density in patients with HHD. In addition, the expression of truncated PPARalpha 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 PPARalpha 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.
Goikoetxea
María J
MJ
Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, 31008 Pamplona, Spain.
Beaumont
Javier
J
González
Arantxa
A
López
Begoña
B
Querejeta
Ramón
R
Larman
Mariano
M
Díez
Javier
J
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics; D000368:Aged; D017209:Apoptosis; D015153:Blotting, Western; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D004452:Echocardiography; D004699:Endocardium / Q000201:enzymology* / Q000473:pathology; D005260:Female; D005355:Fibrosis; D015870:Gene Expression; D006801:Humans; D006973:Hypertension / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047493:PPAR alpha / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis*; D047491:Retinoid X Receptor gamma / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
D047493:PPAR alpha; D020033:Protein Isoforms; D012333:RNA, Messenger; D047491:Retinoid X Receptor gamma; D015094:3-Hydroxyacyl CoA Dehydrogenases; D002334:Carnitine O-Palmitoyltransferase