Activation of LXRα improves cardiac remodeling induced by pulmonary artery hypertension in rats

Gong, Yibo; Yang, Yifeng; Wu, Qin; Gao, Ge; Liu, Yin; Xiong, Yaoyao; Huang, Can; Wu, Sijie

doi:10.1038/s41598-017-04640-6

Cited by 7 publications

(5 citation statements)

References 37 publications

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“…LXRα is also upregulated during cardiac hypertrophy [179,191]. LXR activation reduces cardiac hypertrophy in several models, including TAC in mice [199] and pulmonary artery hypertension (PAH) in rats [200]. In these models, the hypertrophy-limiting effect of LXRα was mediated by the inhibition of the TGFβ and NFκB inflammatory pathways, respectively.…”

Section: Liver X Receptorsmentioning

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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Section: Liver X Receptorsmentioning

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 main characteristics of pulmonary artery hypertension (PAH) are increasing pulmonary artery pressure and irreversible pulmonary vascular remodeling [1, 2] caused by pulmonary artery occlusion. In the pathogenesis of PAH, pulmonary vascular remodeling leads to abnormal trafficking between pulmonary and systemic circulation, resulting in continuous interventricular wall pressure and shear stress [3].…”

Section: Introductionmentioning

confidence: 99%

Trimethoxystilbene Reduces Nuclear Factor Kappa B, Interleukin-6, and Tumor Necrosis Factor-αLevels in Rats with Pulmonary Artery Hypertension

Shu

Liu

Han

et al. 2019

BioMed Research International

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Pulmonary artery hypertension is a refractory disease that severely affects cardiopulmonary function, mainly resulting in irreversible pulmonary vascular remodeling. Current surgical treatment of this disease is not very effective and drug treatment is targeted at relieving symptoms, improving the quality of life of patients, and preventing disease progression. The purpose of this present study was to reveal the regulatory effects of trimethoxystilbene on the serum levels of nuclear factor kappa B, interleukin-6, and tumor necrosis factor-α in a rat model of pulmonary artery hypertension and to explore the possible underlying mechanisms. Healthy Sprague Dawley rats were randomly assigned to experimental groups and treated with monocrotaline to establish the model, and we found a significant difference in the expression levels of nuclear factor kappa B, interleukin-6, and tumor necrosis factor-α between the experimental and control groups. These results suggest that trimethoxystilbene significantly reduced the inflammatory factor levels in pulmonary hypertensive rats, providing us with new potential strategies for elucidating the mechanisms of action of trimethoxystilbene in the treatment of pulmonary artery hypertension.

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“…Cardiac expression of TNF-α and iNOS is also dependent on p38 activity [ 15 , 23 , 24 ] and has been associated with the development of RV hypertrophy and progression to RV failure [ 51 , 52 , 53 , 54 , 55 ]. Increased content of both mediators was found in the SuHx + vehicle group and was normalized by treatment with LASSBio-1824, correlating their expressions to activated p38 levels.…”

Section: Discussionmentioning

confidence: 99%

“…Inhibition of p38 has shown beneficial effects in animal models of both PH and RV failure [ 9 , 12 , 19 , 20 , 21 ]. Activation of p38 is implicated in increased production of inflammatory mediators, such as tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) [ 22 , 23 , 24 ]. In addition, p38 also regulates cell apoptosis mediated by caspases [ 14 , 15 , 16 ], which is an important condition involved in vascular remodeling during PH.…”

Section: Introductionmentioning

confidence: 99%

Novel p38 Mitogen-Activated Protein Kinase Inhibitor Reverses Hypoxia-Induced Pulmonary Arterial Hypertension in Rats

Silva

Alencar

et al. 2022

Pharmaceuticals

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Mitogen-activated protein kinase (MAPK) signaling is strongly implicated in cardiovascular remodeling in pulmonary hypertension (PH) and right ventricle (RV) failure. The effects of a newly designed p38 inhibitor, LASSBio-1824, were investigated in experimentally induced PH. Male Wistar rats were exposed to hypoxia and SU5416 (SuHx), and normoxic rats were used as controls. Oral treatment was performed for 14 days with either vehicle or LASSBio-1824 (50 mg/kg). Pulmonary vascular resistance and RV structure and function were assessed by echocardiography and catheterization. Histological, immunohistochemical and Western blot analysis of lung and RV were performed to investigate cardiovascular remodeling and inflammation. Treatment with LASSBio-1824 normalized vascular resistance by attenuating vessel muscularization and endothelial dysfunction. In the heart, treatment decreased RV systolic pressure, hypertrophy and collagen content, improving cardiac function. Protein content of TNF-α, iNOS, phosphorylated p38 and caspase-3 were reduced both in lung vessels and RV tissues after treatment and a reduced activation of transcription factor c-fos was found in cardiomyocytes of treated SuHx rats. Therefore, LASSBio-1824 represents a potential candidate for remodeling-targeted treatment of PH.

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Activation of LXRα improves cardiac remodeling induced by pulmonary artery hypertension in rats

Cited by 7 publications

References 37 publications

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

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

Trimethoxystilbene Reduces Nuclear Factor Kappa B, Interleukin-6, and Tumor Necrosis Factor-αLevels in Rats with Pulmonary Artery Hypertension

Novel p38 Mitogen-Activated Protein Kinase Inhibitor Reverses Hypoxia-Induced Pulmonary Arterial Hypertension in Rats

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