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Introduction
During the past half-century, great advances in the prevention, diagnosis, and treatment of cardiovascular diseases have been made with the notable exception of heart failure, which is a major global health problem with an estimated prevalence of 38 million patients worldwide [1]. An important cause of heart failure is chronic pressure overload due to aortic stenosis or hypertension, which leads to cardiac hypertrophy that may progress to heart failure. Uncompensated cardiac hypertrophy is characterized by enhanced expression of fetal genes, excessive increase in myocardial mass, abnormal accumulation of extracellular matrix, and severe abnormality of energy metabolism [2-4]. Growing evidence has confirmed that uncompensated cardiac hypertrophy is correlated with an increase in glucose utilization and a decrease in fatty acid utilization (FAU). This metabolic substrate switch seems to involve changes in mRNA level of genes implicated in the transport and metabolism of glucose and fatty acids, which are primarily regulated by a class of nuclear receptors called peroxisome proliferator-activated receptors (PPARs) [3].
PPARα is a key regulator of myocardial fatty acid uptake and oxidation in the heart [5]. During pathological growth of heart failure, down-regulation of FAU genes correlates with decreased PPARα level [6]. It has been shown that activation of PPARα with medium-chain triglycerides is able to prevent the reduction of FAU and reverse the development of cardiac hypertrophy [6, 7]. However, mice with cardiac-restricted overexpression of PPARα (MHC-PPARα) has been shown to develop cardiomyopathy with cardiac dysfunction, and enhanced myocardial lipid accumulation followed by high fat diet (HFD) [5, 8]. Similar to PPARα, PPARβ/δ is also highly expressed in cardiac myocytes and necessary for maintaining myocardial lipid homeostasis [9]. Cardiac PPARβ/δ level was repressed by pressure overload in a hypoxia dependent pathway [10]. Mice with cardiac-specific deletion of the PPARβ/δ has been shown to develop cardiomyopathy with cardiac dysfunction and myocardial lipid accumulation [10, 11]. Conversely, mice with cardiac-restricted overexpression of PPARβ/δ (MHC-PPARβ/δ) did not accumulate myocardial lipid, and exhibited increased myocardial glucose utilization and normal cardiac function [8]. Additionally, reactivation of cardiac PPARβ/δ is sufficient to reverse cardiac hypertrophy in vitro and in vivo [10, 12].
Baicalin (Fig. 1) is is a natural flavone compound abundant in the rhizome of the perennial herb Scutellaria baicalensis, known as huangqin in Chinese traditional...