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 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.
Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, 695011 Kerala, India.
Sreeja
S
Purushothaman
R
R
Renuka Nair
V S
VS
Harikrishnan
A C
AC
Fernandez
D000818:Animals; D001483:Base Sequence; D006332:Cardiomegaly / Q000378:metabolism*; D017931:DNA Primers; D005227:Fatty Acids / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D011918:Rats, Inbred SHR
D017931:DNA Primers; D005227:Fatty Acids
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