scholarly journals Peroxisome Proliferator-Activated Receptor-γIs Critical to Cardiac Fibrosis

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Huang-Jun Liu ◽  
Hai-Han Liao ◽  
Zheng Yang ◽  
Qi-Zhu Tang
Keyword(s):  
Immune Cells ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Receptor Superfamily ◽  
Infarction Heart

Peroxisome proliferator-activated receptor-γ(PPARγ) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily, which plays a central role in regulating lipid and glucose metabolism. However, accumulating evidence demonstrates that PPARγagonists have potential to reduce inflammation, influence the balance of immune cells, suppress oxidative stress, and improve endothelial function, which are all involved in the cellular and molecular mechanisms of cardiac fibrosis. Thus, in this review we discuss the role of PPARγin various cardiovascular conditions associated with cardiac fibrosis, including diabetes mellitus, hypertension, myocardial infarction, heart failure, ischemia/reperfusion injury, atrial fibrillation, and several other cardiovascular disease (CVD) conditions, and summarize the developmental status of PPARγagonists for the clinical management of CVD.

scholarly journals Deletion of soluble epoxide hydrolase enhances coronary reactive hyperemia in isolated mouse heart: role of oxylipins and PPARγ

2016 ◽  
Vol 311 (4) ◽  
pp. R676-R688 ◽  
Author(s):  
Ahmad Hanif ◽  
Matthew L. Edin ◽  
Darryl C. Zeldin ◽  
Christophe Morisseau ◽  
Mohammed A. Nayeem
Keyword(s):  
Epoxide Hydrolase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Reactive Hyperemia ◽  
Soluble Epoxide Hydrolase ◽  
Mouse Heart ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist

The relationship between soluble epoxide hydrolase (sEH) and coronary reactive hyperemia (CRH) response to a brief ischemic insult is not known. Epoxyeicosatrienoic acids (EETs) exert cardioprotective effects in ischemia/reperfusion injury. sEH converts EETs into dihydroxyeicosatrienoic-acids (DHETs). Therefore, we hypothesized that knocking out sEH enhances CRH through modulation of oxylipin profiles, including an increase in EET/DHET ratio. Compared with sEH+/+, sEH−/− mice showed enhanced CRH, including greater repayment volume (RV; 28% higher, P < 0.001) and repayment/debt ratio (32% higher, P < 0.001). Oxylipins from the heart perfusates were analyzed by LC-MS/MS. The 14,15-EET/14,15-DHET ratio was 3.7-fold higher at baseline ( P < 0.001) and 5.6-fold higher post-ischemia ( P < 0.001) in sEH−/− compared with sEH+/+ mice. Likewise, the baseline 9,10- and 12,13-EpOME/DiHOME ratios were 3.2-fold ( P < 0.01) and 3.7-fold ( P < 0.001) higher, respectively in sEH−/− compared with sEH+/+ mice. 13-HODE was also significantly increased at baseline by 71% ( P < 0.01) in sEH−/− vs. sEH+/+ mice. Levels of 5-, 11-, 12-, and 15-hydroxyeicosatetraenoic acids were not significantly different between the two strains ( P > 0.05), but were decreased postischemia in both groups ( P = 0.02, P = 0.04, P = 0.05, P = 0.03, respectively). Modulation of CRH by peroxisome proliferator-activated receptor gamma (PPARγ) was demonstrated using a PPARγ-antagonist (T0070907), which reduced repayment volume by 25% in sEH+/+ ( P < 0.001) and 33% in sEH−/− mice ( P < 0.01), and a PPARγ-agonist (rosiglitazone), which increased repayment volume by 37% in both sEH+/+ ( P = 0.04) and sEH−/− mice ( P = 0.04). l-NAME attenuated CRH in both sEH−/− and sEH+/+. These data demonstrate that genetic deletion of sEH resulted in an altered oxylipin profile, which may have led to an enhanced CRH response.

The Role of Peroxisome Proliferator-Activated Receptor γ in Mediating Cardioprotection Against Ischemia/Reperfusion Injury

2017 ◽  
Vol 23 (1) ◽  
pp. 46-56 ◽  
Author(s):  
Chong-Bin Zhong ◽  
Xi Chen ◽  
Xu-Yue Zhou ◽  
Xian-Bao Wang
Keyword(s):  
Lipid Metabolism ◽  
Target Genes ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose And Lipid Metabolism ◽  
Cardioprotective Effects

Myocardial infarction (MI) is a serious cardiovascular disease resulting in high rates of morbidity and mortality. Although advances have been made in restoring myocardial perfusion in ischemic areas, decreases in cardiomyocyte death and infarct size are still limited, attributing to myocardial ischemia/reperfusion (I/R) injury. It is necessary to develop therapies to restrict myocardial I/R injury and protect cardiomyocytes against further damage after MI. Many studies have suggested that peroxisome proliferator-activated receptor γ (PPARγ), a ligand-inducible nuclear receptor that predominantly regulates glucose and lipid metabolism, is a promising therapeutic target for ameliorating myocardial I/R injury. Thus, this review focuses on the role of PPARγ in cardioprotection during myocardial I/R. The cardioprotective effects of PPARγ, including attenuating oxidative stress, inhibiting inflammatory responses, improving glucose and lipid metabolism, and antagonizing apoptosis, are described. Additionally, the underlying mechanisms of cardioprotective effects of PPARγ, such as regulating the expression of target genes, influencing other transcription factors, and modulating kinase signaling pathways, are further discussed.

scholarly journals A Role for PPARγin the Regulation of Cytokines in Immune Cells and Cancer

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-12 ◽  
Author(s):  
Xiao Yi Yang ◽  
Li Hua Wang ◽  
William L. Farrar
Keyword(s):  
Immune Cells ◽  
Cellular Differentiation ◽  
Cytokine Production ◽  
Peroxisome Proliferator ◽  
Biological Functions ◽  
Inhibit Tumor Growth ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Receptor Superfamily ◽  
Abundant Evidence ◽  
Important Regulator

Peroxisome proliferator-activated receptorγ(PPARγ) is a ligand-activated transcription factor and a member of the nuclear receptor superfamily. PPARγand its ligands appear to serve diverse biological functions. In addition to the well-studied effects of PPARγon metabolism and cellular differentiation, abundant evidence suggests that PPARγis an important regulator of the immune system and cancers. Since cytokines are not only key modulators of inflammation with pro- and anti-inflammatory functions but they also can either stimulate or inhibit tumor growth and progression, this review summarizes the role for PPARγin the regulation of cytokine production and cytokine-mediated signal transduction pathways in immune cells and cancer.

scholarly journals Emerging Role of Ferroptosis in the Pathogenesis of Ischemic Stroke: A New Therapeutic Target?

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110375
Author(s):  
Zhong-Qi Bu ◽  
Hai-Yang Yu ◽  
Jue Wang ◽  
Xin He ◽  
Yue-Ran Cui ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
High Morbidity ◽  
Treatment And Prevention ◽  
Regulated Cell Death ◽  
Programmed Death ◽  
Research Findings

Ischemic stroke is one of the main causes of high morbidity, mortality, and disability worldwide; however, the treatment methods are limited and do not always achieve satisfactory results. The pathogenesis of ischemic stroke is complex, defined by multiple mechanisms; among them, programmed death of neuronal cells plays a significant role. Ferroptosis is a novel type of regulated cell death characterized by iron redistribution or accumulation and increased lipid peroxidation in the membrane. Ferroptosis is implicated in many pathological conditions, such as cancer, neurodegenerative diseases, and ischemia-reperfusion injury. In this review, we summarize current research findings on ferroptosis, including possible molecular mechanisms and therapeutic applications of ferroptosis regulators, with a focus on the involvement of ferroptosis in the pathogenesis and treatment of ischemic stroke. Understanding the role of ferroptosis in ischemic stroke will throw some light on the development of methods for diagnosis, treatment, and prevention of this devastating disease.

scholarly journals Disruption of hepatic small heterodimer partner induces dissociation of steatosis and inflammation in experimental nonalcoholic steatohepatitis

2019 ◽  
Vol 295 (4) ◽  
pp. 994-1008 ◽  
Author(s):  
Nancy Magee ◽  
An Zou ◽  
Priyanka Ghosh ◽  
Forkan Ahamed ◽  
Don Delker ◽  
...  
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Molecular Mechanisms ◽  
Liver Steatosis ◽  
Chow Diet ◽  
Peroxisome Proliferator ◽  
Rna Seq ◽  
Hepatic Inflammation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Small Heterodimer Partner

Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease worldwide and is characterized by steatosis, inflammation, and fibrosis. The molecular mechanisms underlying NASH development remain obscure. The nuclear receptor small heterodimer partner (Shp) plays a complex role in lipid metabolism and inflammation. Here, we sought to determine SHP's role in regulating steatosis and inflammation in NASH. Shp deletion in murine hepatocytes (ShpHep−/−) resulted in massive infiltration of macrophages and CD4+ T cells in the liver. ShpHep−/− mice developed reduced steatosis, but surprisingly increased hepatic inflammation and fibrosis after being fed a high-fat, -cholesterol, and -fructose (HFCF) diet. RNA-Seq analysis revealed that pathways involved in inflammation and fibrosis are significantly activated in the liver of ShpHep−/− mice fed a chow diet. After having been fed the HFCF diet, WT mice displayed up-regulated peroxisome proliferator-activated receptor γ (Pparg) signaling in the liver; however, this response was completely abolished in the ShpHep−/− mice. In contrast, livers of ShpHep−/− mice had consistent NF-κB activation. To further characterize the role of Shp specifically in the transition of steatosis to NASH, mice were fed the HFCF diet for 4 weeks, followed by Shp deletion. Surprisingly, Shp deletion after steatosis development exacerbated hepatic inflammation and fibrosis without affecting liver steatosis. Together, our results indicate that, depending on NASH stage, hepatic Shp plays an opposing role in steatosis and inflammation. Mechanistically, Shp deletion in hepatocytes activated NF-κB and impaired Pparg activation, leading to the dissociation of steatosis, inflammation, and fibrosis in NASH development.

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