Browsing by Author "Ismael, S"

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    Ligand specific variation in cardiac response to stimulation of peroxisome proliferator-activated receptor-alpha in spontaneously hypertensive rat
    (MOLECULAR AND CELLULAR BIOCHEMISTRY, 2015) Ismael, S; Purushothaman, S; Harikrishnan, VS; Nair, RR
    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-alpha). 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-alpha can reduce cardiac remodeling in spontaneously hypertensive rat (SHR). Cardiac response to stimulation of PPAR-alpha presumably depends on the type of ligand used. Therefore, the study was carried out in SHR, using two different PPAR-alpha ligands. SHR were treated with either fenofibrate (100 mg/kg/day) or medium-chain triglyceride (MCT) Tricaprylin (5 % of diet) for 4 months. Expression of PPAR-alpha and medium-chain acylCoA dehydrogenase served as markers, for stimulation of PPAR-alpha. Both ligands stimulated PPAR-alpha. 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-alpha is detrimental; the study substantiates that cardiac response to stimulation of PPAR-alpha is ligand specific.
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    Metabolic Modulation by Medium-Chain Triglycerides Reduces Oxidative Stress and Ameliorates CD36-Mediated Cardiac Remodeling in Spontaneously Hypertensive Rat in the Initial and Established Stages of Hypertrophy
    (J Cardiac failure, 2017-03) Ismael, S; Lakshmi, S; Remani, K; Nair, RR
    Background: Left ventricular hypertrophy (LVH) is characterized by a decrease in oxidation of longchain fatty acids, possibly mediated by reduced expression of the cell-surface protein cluster of differentiation 36 (CD36). Spontaneously hypertensive rats (SHRs) were therefore supplemented with medium-chain triglycerides (MCT), a substrate that bypasses CD36, based on the assumption that the metabolic modulation will ameliorate ventricular remodeling. Methods: The diet of 2-month-old and 6-month-old SHRs was supplemented with 5% MCT (Tricaprylin), for 4 months. Metabolic modulation was assessed by mRNA expression of peroxisome proliferator– activated receptor α and medium-chain acyl-CoA dehydrogenase. Blood pressure was measured noninvasively. LVH was assessed with the use of hypertrophy index, cardiomyocyte cross-sectional area, mRNA expression of B-type natriuretic peptide, cardiac fibrosis, and calcineurin-A levels. Oxidative stress indicators (cardiac malondialdehyde, protein carbonyl, and 3-nitrotyrosine levels), myocardial energy level (ATP, phosphocreatine), and lipid profile were determined. Results: Supplementation of MCT stimulated fatty acid oxidation in animals of both age groups, reduced hypertrophy and oxidative stress along with the maintenance of energy level. Blood pressure, body weight, and lipid profile were unaffected by the treatment. Conclusions: The results indicate that modulation of myocardial fatty acid metabolism by MCT prevents progressive cardiac remodeling in SHRs, possibly by maintenance of energy level and decrease in oxidative stress. (J Cardiac Fail 2017;23:240–251)