Browsing by Author "Purushothaman, Sreeja"

Now showing 1 - 3 of 3
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    Association of PPARalpha Intron 7 Polymorphism with Coronary Artery Disease: A Cross-Sectional Study.
    (ISRN cardiology, 2011)
    The allelic variants of peroxisome proliferator-activated receptor alpha (PPARalpha) can influence the risk of coronary artery disease (CAD) by virtue of its effect on lipid metabolism. However, the role of PPARalpha intronic polymorphism with CAD has received little attention. The association of allelic variants G/C at intron 7 of the PPAR-alpha gene with CAD was examined in a hospital-based Indian population. PPAR genotyping was performed in 110 male patients with CAD and 120 age and ethnically matched healthy males by PCR amplification of the gene followed by restriction digestion. Presence of C allele showed a positive association with CAD (OR = 2.9; 95% CI [1.65-4.145]; P = .009) and also with dyslipidaemia (OR = 2.95, 95% CI (1.5-4.39); P < .05). Impaired lipid metabolism in carriers of the PPARalpha Intron 7C allele is possibly responsible for the predilection to CAD.
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    Reactivation of Peroxisome Proliferator-activated Receptor Alpha in Spontaneously Hypertensive Rat: Age-associated Paradoxical Effect on the Heart
    (JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 2011)
    Prevention of left ventricular hypertrophy remains a challenge in the prevention of hypertension-induced adverse cardiac remodeling. Cardiac hypertrophy is associated with a shift in energy metabolism from predominantly fatty acid to glucose with a corresponding reduction in the expression of fatty acid oxidation enzyme genes. Although initially adaptive, the metabolic switch seems to be detrimental in the long run. This study was taken up with the objective of examining whether the stimulation of fatty acid oxidation by the activation of peroxisome proliferator-activated receptor alpha PPAR alpha), a key regulator of fatty acid metabolism, can prevent cardiac hypertrophy. Fenofibrate was used as the PPAR alpha agonist. Spontaneously hypertensive rats (SHRs) in the initial stages of hypertrophy (2 months) and those with established hypertrophy (6 months) were treated with fenofibrate (100 mg.kg(-1).d(-1) for 60 days). Cluster of differentiation 36 (CD36)-responsible for myocardial fatty acid uptake, carnitine palmitoyl transferase 1 beta-a mitochondrial transporter protein and medium chain acyl-Co-A dehydrogenase-a key enzyme in beta oxidation of fatty acids were selected as indicators of fatty acid metabolism. Hypertrophy was apparent at 2 months and metabolic shift at 4 months of age in SHRs. The treatment prevented cardiac remodeling in young animals but aggravated hypertrophy in older animals. Hypertrophy showed a positive association with malondialdehyde levels and cardiac NF-kappa B gene expression, signifying the role of oxidative stress in the mediation of hypertrophy. Expression of carnitine palmitoyl transferase 1 beta and medium chain acyl-Co-A dehydrogenase was upregulated on treatment. However, CD36 showed an age-dependent variation on treatment, with no change in expression in young rats and downregulation in older animals. It is inferred that the stimulation of PPAR alpha before the initiation of metabolic remodeling may prevent cardiac hypertrophy, but reactivation after the metabolic adaptation aggravates hypertrophy. Whether the down-regulation of CD36 is mediated by decreased substrate availability remains to be explored. Age-dependent paradoxical effect on the heart in response to fenofibrate, used as a lipid-lowering drug, can have therapeutic implications.
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    Temporal relation of cardiac hypertrophy, oxidative stress, and fatty acid metabolism in spontaneously hypertensive rat
    (MOLECULAR AND CELLULAR BIOCHEMISTRY, 2011)
    Left ventricular hypertrophy is an adaptive response to hypertension, and an independent clinical risk factor for cardiac failure, sudden death, and myocardial infarction. As regression of cardiac hypertrophy is associated with a lower likelihood of cardiovascular events, it is recognized as a target of antihypertensive therapy. This necessitates identification of factors associated with the initiation and progression of hypertrophy. Oxidative stress and metabolic shift are intimately linked with myocardial hypertrophy, but their interrelationship is not clearly understood. This study proposes to identify the temporal sequence of events so as to distinguish whether oxidative stress and metabolic shift are a cause or consequence of hypertrophy. Spontaneously hypertensive rat (SHR) was used as the experimental model. Cardiac hypertrophy was apparent at 2 months of age, as assessed by hypertrophy index and brain natriuretic peptide gene expression. Enhanced myocardial lipid peroxidation accompanied by nuclear factor-kappa B gene expression in one-month-old SHR suggests that oxidative stress precedes the development of hypertrophy. Metabolic shift identified by reduction in the expression of peroxisome proliferator-activated receptor-alpha, medium chain acyl CoA dehydrogenase, and carnitine palmitoyltransferase 1 beta was seen at 4 months of age, implying that reduction of fatty acid oxidation is a consequence of hypertrophy. Information on the temporal sequence of events associated with hypertrophy will help in the prevention and reversal of cardiac remodeling. Investigations aimed at prevention of hypertrophy should address reduction of oxidative stress. Both, oxidative stress and metabolic modulation have to be considered for studies that focus on the regression of hypertrophy.