Activation of peroxisome proliferator-activated receptor-α and -γ 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. Aims: 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. 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 front lCM 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 nonfailing 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 lCM patients and might be functionally important in the maintenance of atrial morphology. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.