caa a22 4500 606236112 CHVBK 20210128101246.0 cr unu---uuuuu 210128e20150801xx s 000 0 eng 10.1007/s11010-015-2435-x doi (NATIONALLICENCE)springer-10.1007/s11010-015-2435-x Ligand specific variation in cardiac response to stimulation of peroxisome proliferator-activated receptor-alpha in spontaneously hypertensive rat [Elektronische Daten] [Saifudeen Ismael, Sreeja Purushothaman, V. Harikrishnan, R. Nair] Left ventricular hypertrophy (LVH) is an independent risk factor for cardiac failure. Reduction of LVH has beneficial effects on the heart. LVH is associated with shift in energy substrate preference from fatty acid to glucose, mediated by down regulation of peroxisome proliferator-activated receptor-alpha (PPAR-α). As long-term dependence on glucose can promote adverse cardiac remodeling, it was hypothesized that, prevention of metabolic shift by averting down regulation of PPAR-α can reduce cardiac remodeling in spontaneously hypertensive rat (SHR). Cardiac response to stimulation of PPAR-α presumably depends on the type of ligand used. Therefore, the study was carried out in SHR, using two different PPAR-α ligands. SHR were treated with either fenofibrate (100mg/kg/day) or medium-chain triglyceride (MCT) Tricaprylin (5% of diet) for 4months. Expression of PPAR-α and medium-chain acylCoA dehydrogenase served as markers, for stimulation of PPAR-α. Both ligands stimulated PPAR-α. Decrease of blood pressure was observed only with fenofibrate. LVH was assessed from heart-weight/body weight ratio, histology and brain natriuretic peptide expression. As oxidative stress is linked with hypertrophy, serum and cardiac malondialdehyde and cardiac 3-nitrotyrosine levels were determined. Compared to untreated SHR, LVH and oxidative stress were lower on supplementation with MCT, but higher on treatment with fenofibrate. The observations indicate that reduction of blood pressure is not essentially accompanied by reduction of LVH, and that, progressive cardiac remodeling can be prevented with decrease in oxidative stress. Contrary to the notion that reactivation of PPAR-α is detrimental; the study substantiates that cardiac response to stimulation of PPAR-α is ligand specific. Springer Science+Business Media New York, 2015 Cardiac remodeling nationallicence Metabolic shift nationallicence Stimulation of PPAR- α nationallicence Fenofibrate nationallicence Medium chain triglyceride nationallicence Oxidative stress nationallicence Ismael Saifudeen Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, 695011, Thiruvananthapuram, India aut Purushothaman Sreeja Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, 695011, Thiruvananthapuram, India aut Harikrishnan V. Division of Laboratory Animal Sciences, Sree Chitra Tirunal Institute for Medical Sciences and Technology, 695011, Thiruvananthapuram, India aut Nair R. Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, 695011, Thiruvananthapuram, India aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 406/1-2(2015-08-01), 173-182 0300-8177 406:1-2<173 2015 406 11010 https://doi.org/10.1007/s11010-015-2435-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2435-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ismael Saifudeen Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, 695011, Thiruvananthapuram, India aut NATIONALLICENCE 700 1- Purushothaman Sreeja Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, 695011, Thiruvananthapuram, India aut NATIONALLICENCE 700 1- Harikrishnan V. Division of Laboratory Animal Sciences, Sree Chitra Tirunal Institute for Medical Sciences and Technology, 695011, Thiruvananthapuram, India aut NATIONALLICENCE 700 1- Nair R. Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, 695011, Thiruvananthapuram, India aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 406/1-2(2015-08-01), 173-182 0300-8177 406:1-2<173 2015 406 11010