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

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Abstract

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 1β 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.

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Acknowledgments

The financial support extended by Kerala State Science Technology and Environment Council is gratefully acknowledged. Ms. Sreeja Purushothaman was the recipient of Research Fellowship from the Council of Scientific and Industrial Research, India. Real time RT-PCR analysis was carried out at the Rubber Research Institute of India, Rubber Board, Kottayam, India. The authors are grateful to the Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India, for the facilities to carry out the study and permission to publish the findings.

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Authors and Affiliations

  1. Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, 695 011, Kerala, India

    Sreeja Purushothaman & R. Renuka Nair

  2. Division of Laboratory Animal Science, Bio Medical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, 695012, Kerala, India

    V. S. Harikrishnan & A. C. Fernandez

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  1. Sreeja Purushothaman
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  2. R. Renuka Nair
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  3. V. S. Harikrishnan
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  4. A. C. Fernandez
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Correspondence to R. Renuka Nair.

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Purushothaman, S., Renuka Nair, R., Harikrishnan, V.S. et al. Temporal relation of cardiac hypertrophy, oxidative stress, and fatty acid metabolism in spontaneously hypertensive rat. Mol Cell Biochem 351, 59–64 (2011). https://doi.org/10.1007/s11010-011-0711-y

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  • DOI: https://doi.org/10.1007/s11010-011-0711-y

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