Activation of peroxisome proliferator-activated receptor-alpha and -gamma in auricular tissue from heart failure patients.
OBJECTIVE
Peroxisome proliferator-activated receptors (PPARs), key transcriptional regulators of lipid and energy metabolism in cardiomyocytes, have recently been proposed to modulate cardiovascular pathophysiological responses in experimental models. However, there is little information about the functional activity of PPARs in human heart failure.


OBJECTIVE
To investigate PPAR-alpha and -gamma expression and activity, and the association with ET-1 production and fibrosis, in cardiac biopsies from patients with end-stage heart failure due to ischemic cardiomyopathy (ICM) in comparison and from non-failing donor hearts. All samples were obtained during cardiac transplantation.


RESULTS
Morphological analysis (by Masson trichrome and image analysis) did not detect fibrosis in the left atrium from non-failing donors (NFLA) or from ICM patients (FLA). However, left ventricles from failing hearts (FLV) contained a greater number of fibrotic areas (NFLA: 3.21+/-1.15, FLA: 1.63+/-0.83, FLV: 14.5+/-3.45%; n = 9, P<0.05). By RT-PCR, preproET-1 expression was similar in the non-failing and failing atrium but was significantly higher in the ventricles from failing hearts (NFLA: 1.00+/-0.06, FLA: 1.08+/-0.11, FLV: 1.74+/-0.19; n = 9, P<0.05). PPAR-alpha and PPAP-gamma mRNA (by RT-PCR) and protein (by Western blot) levels were higher in the ventricles from failing hearts compared with the atrium from failing and non-failing hearts. Electrophoretic mobility shift assays showed that PPAR-alpha and PPAP-gamma were not activated in the ventricles (NFLA: 1.00+/-0.11, FLA: 1.89+/-0.24, FLV: 0.95+/-0.07; n = 9, P<0.05).


CONCLUSIONS
These data suggest that PPAR-alpha and PPAP-gamma are selectively activated in the atria from ICM patients and might be functionally important in the maintenance of atrial morphology.
Gómez-Garre
Dulcenombre
D
Vascular Biology and Atherosclerosis Research Laboratory, Area de Prevención Cardiovascular y Rehabilitación Cardíaca, Instituto Cardiovascular, Spain. mgomezg.hcsc@salud.madrid.org
Herraíz
Marta
M
González-Rubio
Ma Luisa
ML
Bernal
Rosa
R
Aragoncillo
Paloma
P
Carbonell
Amparo
A
Rufilanchas
Juan José
JJ
Fernández-Cruz
Arturo
A
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D015153:Blotting, Western; D016022:Case-Control Studies; D002648:Child; D019332:Endothelin-1 / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005355:Fibrosis; D015870:Gene Expression; D006325:Heart Atria / Q000378:metabolism* / Q000473:pathology; D006333:Heart Failure / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019332:Endothelin-1; D047493:PPAR alpha; D047495:PPAR gamma; D012333:RNA, Messenger