Temporal relation of cardiac hypertrophy, oxidative stress, and fatty acid metabolism in spontaneously hypertensive rat.

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 1ß 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.

Association of PPARα Intron 7 Polymorphism with Coronary Artery Disease: A Cross-Sectional Study.

The allelic variants of peroxisome proliferator-activated receptor alpha (PPARα) can influence the risk of coronary artery disease (CAD) by virtue of its effect on lipid metabolism. However, the role of PPARα 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 PPARα Intron 7C allele is possibly responsible for the predilection to CAD.

AB0 blood group incompatibility and inbreeding effects: evidence for an interaction.

It is known that consanguinity reduces the chances of maternal-foetal incompatibility but it is not known whether inbreeding influences the expression of the effects of such incompatibility. This paper investigates and finds evidence for an interaction between inbreeding and AB0 blood group incompatibility on the expression of neonatal mortality, sibship precocious mortality, neonatal jaundice, asphyxia, and sex ratio, through screening of 3923 consecutive newborns. Inbreeding and incompatibility individually showed variable effects on the above parameters, but their interaction was such that, in the presence of inbreeding, incompatibility reduced the incidence/relative risk of all the above factors. Such a uniform negative interaction was presumed to be due to homozygosity of some pleiotropic genes caused by inbreeding.