Ligand specific variation in cardiac response to stimulation of peroxisome proliferator-activated receptor-alpha in spontaneously hypertensive rat

Ismael, Saifudeen; Purushothaman, Sreeja; Harikrishnan, V. S.; Nair, R. V.

doi:10.1007/s11010-015-2435-x

Cited by 16 publications

(8 citation statements)

References 47 publications

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“…Previous studies demonstrated that abnormalities in cardiac lipid metabolism and energy production is a consistent feature of heart failure [30, 35]. Crucially, the progression of heart failure with pressure overload is associated with decreased PPARα and PPARβ/δ, and reactivation of PPARα, or PPARβ/δ, is sufficient to reverse myocardial dysfunction and hypertrophy, respectively [5, 7, 8, 10]. In the present study, we found myocardial dysfunction was ameliorated by baicalin treatment in TAC hearts, accompanied by reduced myocardial fibrosis, apoptosis signals, and profound restoration of PPARα and PPARβ/δ.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, we found that baicalin attenuated cardiac hypertrophy in response to hypertrophic stimuli, accompanied by restoration of PPARα and PPARβ/δ. Previously, reactivation of PPARα with different ligands exhibited opposite effects on left ventricular hypertrophy in spontaneously hypertensive rat [7]. However, the protective effects of cardiac PPARβ/δ restoration on cardiac hypertrophy were clearly demonstrated in vitro and in vivo [10, 12].…”

Section: Discussionmentioning

confidence: 99%

“…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].…”

Section: Introductionmentioning

confidence: 99%

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Baicalin Attenuates Cardiac Dysfunction and Myocardial Remodeling in a Chronic Pressure-Overload Mice Model

Zhang

Liao

Zhu

et al. 2017

Cell Physiol Biochem

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Background/Aims: Baicalin has been shown to be effective for various animal models of cardiovascular diseases, such as pulmonary hypertension, atherosclerosis and myocardial ischaemic injury. However, whether baicalin plays a role in cardiac hypertrophy remains unknown. Here we investigated the protective effects of baicalin on cardiac hypertrophy induced by pressure overload and explored the potential mechanisms involved. Methods: C57BL/6J-mice were treated with baicalin or vehicle following transverse aortic constriction or Sham surgery for up to 8 weeks, and at different time points, cardiac function and heart size measurement and histological and biochemical examination were performed. Results: Mice under pressure overload exhibited cardiac dysfunction, high mortality, myocardial hypertrophy, increased apoptosis and fibrosis markers, and suppressed cardiac expression of PPARα and PPARβ/δ. However, oral administration of baicalin improved cardiac dysfunction, decreased mortality, and attenuated histological and biochemical changes described above. These protective effects of baicalin were associated with reduced heart and cardiomyocyte size, lower fetal genes expression, attenuated cardiac fibrosis, lower expression of profibrotic markers, and decreased apoptosis signals in heart tissue. Moreover, we found that baicalin induced PPARα and PPARβ/δ expression in vivo and in vitro. Subsequent experiments demonstrated that long-term baicalin treatment presented no obvious cardiac lipotoxicity. Conclusions: The present results demonstrated that baicalin attenuates pressure overload induced cardiac dysfunction and ventricular remodeling, which would be due to suppressed cardiac hypertrophy, fibrosis, apoptosis and metabolic abnormality.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Baicalin Attenuates Cardiac Dysfunction and Myocardial Remodeling in a Chronic Pressure-Overload Mice Model

Zhang

Liao

Zhu

et al. 2017

Cell Physiol Biochem

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show abstract

“…However, cardiac PPARα expression was unchanged in a model of abdominal aortic banding [38], revealing that the regulation of cardiomyocyte hypertrophy is strongly reliant on the stress source. In hypertensive rats treated with the PPARα agonist medium-chain triglyceride tricaprylin, PPARα activation reduced cardiac oxidative stress without affecting blood pressure [140]. More recently, Harvey and colleagues showed that phenylephrine-induced hypertrophy in H9c2 cardiomyocytes reduces PPARα expression while increasing NOX2 expression and activity [141].…”

Section: Pparαmentioning

confidence: 99%

Untangling the Cooperative Role of Nuclear Receptors in Cardiovascular Physiology and Disease

Paredes¹,

Santos-Clemente²,

Ricote³

2021

IJMS

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The heart is the first organ to acquire its physiological function during development, enabling it to supply the organism with oxygen and nutrients. Given this early commitment, cardiomyocytes were traditionally considered transcriptionally stable cells fully committed to contractile function. However, growing evidence suggests that the maintenance of cardiac function in health and disease depends on transcriptional and epigenetic regulation. Several studies have revealed that the complex transcriptional alterations underlying cardiovascular disease (CVD) manifestations such as myocardial infarction and hypertrophy is mediated by cardiac retinoid X receptors (RXR) and their partners. RXRs are members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors and drive essential biological processes such as ion handling, mitochondrial biogenesis, and glucose and lipid metabolism. RXRs are thus attractive molecular targets for the development of effective pharmacological strategies for CVD treatment and prevention. In this review, we summarize current knowledge of RXR partnership biology in cardiac homeostasis and disease, providing an up-to-date view of the molecular mechanisms and cellular pathways that sustain cardiomyocyte physiology.

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“…MCAD regulates the first step in the reaction of fatty acid β-oxidation, namely conversion of acyl-coenzyme A into trans -enoyl-CoA [ 36 ]. The synthesis of MCPT1 and MCAD is regulated by nuclear factor PPARα the activation of which promotes the expression of downstream genes, namely, the MCPT1 and MCAD [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV inhibits ventricular remodeling and improves fatty acid utilization in rats with chronic heart failure

et al. 2018

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Chronic heart failure (CHF) is the end-stage of many cardiovascular diseases and severely affects the patients’ lifespan. Inhibiting ventricular remodeling is thus a primary treatment target for CHF patients. Astragaloside IV (AS-IV) can improve cardiac function and protect myocardial cells. The study aims to investigate the effects of AS-IV on ventricular remodeling and explore its role in regulating energy metabolism using a rat CHF model. Sprague–Dawley rats were divided into five groups (n=20 per group): CHF + benazepril hydrochloride (Benazepril HCL), CHF + low-dose (30 mg.kg−1.day−1) AS-IV, CHF + high-dose (60 mg.kg−1.day−1) AS-IV, and a sham control group. After 8 weeks of treatment, the cardiac structure and functional parameters were measured. Morphological changes in the myocardial tissue in five groups were evaluated. Protein and mRNA expression of peroxisome proliferator-activated receptor α (PPARα), medium-chain acyl-CoA dehydrogenase (MCAD), and muscle carnitine palmitoyl transferase-1 (MCPT1) were also analyzed. Our results showed that the left ventricular mass index (LVMI), collagen volume fraction (CVF), and free fatty acid (FFA) concentration of CHF group rats increased when compared with sham control group, while the protein and mRNA expressions of PPARα, MCAD, and MCPT1 decreased in CHF. Importantly, treatment with AS-IV (CHF + AS-IV group) showed improved heart function and structure, increased expression of PPARα, MCAD, and MCPT1 and improved FFA utilization in comparison with CHF group. In conclusion, our study shows that AS-IV inhibits ventricular remodeling, improves cardiac function, and decreases FFA concentration of CHF model rats. Our findings suggest a therapeutic potential of using AS-IV in CHF.

show abstract

Ligand specific variation in cardiac response to stimulation of peroxisome proliferator-activated receptor-alpha in spontaneously hypertensive rat

Cited by 16 publications

References 47 publications

Baicalin Attenuates Cardiac Dysfunction and Myocardial Remodeling in a Chronic Pressure-Overload Mice Model

Baicalin Attenuates Cardiac Dysfunction and Myocardial Remodeling in a Chronic Pressure-Overload Mice Model

Untangling the Cooperative Role of Nuclear Receptors in Cardiovascular Physiology and Disease

Astragaloside IV inhibits ventricular remodeling and improves fatty acid utilization in rats with chronic heart failure

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