AimsAlthough statins may provide potential therapeutic pathways for patients with heart failure with preserved ejection fraction (HFpEF), no studies have evaluated statins in combination with standard HF therapy, which would reflect clinical practice more closely. To address this question, we evaluated whether rosuvastatin added to a standard HF therapy provides additional improvement in cardiac structure and function in rats with hypertensive heart failure (SHHF). Methods and resultsTwo-month-old SHHF rats were randomly assigned to four groups: (i) non-treated SHHF rats; (ii) rosuvastatintreated SHHF rats; (iii) SHHF rats treated with quinapril plus torasemide plus carvedilol (considered as standard HF therapy); and (iv) SHHF rats treated with the combination of standard HF therapy and rosuvastatin. The administration of a standard anti-hypertensive HF therapy to SHHF rats for 17 months attenuated left ventricular (LV) chamber dilatation, cardiac hypertrophy, fibrosis, and inflammation compared with non-treated SHHF rats. Rosuvastatin alone prevented LV dilatation and cardiac inflammation similar to standard HF therapy-treated SHHF, despite being unable to normalize blood pressure (BP) or influence cardiac hypertrophy. However, and importantly, the addition of rosuvastatin to the standard HF therapy further prevented LV dilatation, preserved cardiac function, and normalized inflammation. ConclusionThese data show that the use of rosuvastatin plus a standard HF therapy results in a significant additional improvement in HF and cardiac remodelling in a rat model of HFpEF. These beneficial effects were independent of BP and plasma lipid changes, and seem to be due, at least in part, to decreased myocardial inflammation.--

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-a and -g 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 nonfailing donors (NFLA) or from ICM patients (FLA). However, left ventricles from failing hearts (FLV) contained a greater number of fibrotic areas (NFLA: 3.21 T1.15, FLA: 1.63 T 0.83, FLV: 14.5 T 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 T 0.06, FLA: 1.08 T 0.11, FLV: 1.74 T 0.19; n = 9, P < 0.05). PPAR-a and PPAP-g 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-a and PPAP-g were not activated in the ventricles (NFLA: 1.00 T 0.11, FLA: 1.89 T 0.24, FLV: 0.95 T 0.07; n = 9, P < 0.05). Conclusions: These data suggest that PPAR-a and PPAP-g are selectively activated in the atria from ICM patients and might be functionally important in the maintenance of atrial morphology.