© 2006 European Society of Cardiology
Activation of peroxisome proliferator-activated receptor-
and -
in auricular tissue from heart failure patients
a Vascular Biology and Atherosclerosis Research Laboratory, Área de Prevención Cardiovascular y Rehabilitación Cardíaca, Instituto Cardiovascular Spain
b Department of Pathology, Hospital Clínico San Carlos-UCM Spain
c Heart Failure and Transplant Unit, Cardiology Department Hospital 12 de Octubre-UCM, Madrid, Spain
* Corresponding author. Laboratorio de Biología vascular y Arteriosclerosis (Medicina Nuclear-sótano norte), Hospital Clínico San Carlos, C/Martín Lagos s/n, 28040-Madrid, Spain. Tel.: +34 91 330 3000x7364. E-mail address: mgomezg.hcsc{at}salud.madrid.org
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Abstract |
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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.
Aims: To investigate PPAR-
and -
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.
Methods and 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- and PPAP- 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- and PPAP- 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- and PPAP- are selectively activated in the atria from ICM patients and might be functionally important in the maintenance of atrial morphology.
Key Words: Heart failure • Atrium • Endothelin-1 • Cardiac remodelling • Nuclear receptors
Received November 12, 2004; Accepted June 6, 2005
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