scholarly journals PPARγand Its Role in Cardiovascular Diseases

PPAR Research ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Mini Chandra ◽  
Sumitra Miriyala ◽  
Manikandan Panchatcharam
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular Events ◽  
Current Knowledge ◽  
Peroxisome Proliferator ◽  
Cardiovascular Disorders ◽  
Cellular Functions ◽  
Peroxisome Proliferator Activated Receptor ◽  
Treatment Of Diabetes ◽  
Potential Therapeutics

Peroxisome proliferator-activated receptor Gamma (PPARγ), a ligand-activated transcription factor, has a role in various cellular functions as well as glucose homeostasis, lipid metabolism, and prevention of oxidative stress. The activators of PPARγare already widely used in the treatment of diabetes mellitus. The cardioprotective effect of PPARγactivation has been studied extensively over the years making them potential therapeutic targets in diseases associated with cardiovascular disorders. However, they are also associated with adverse cardiovascular events such as congestive heart failure and myocardial infarction. This review aims to discuss the role of PPARγin the various cardiovascular diseases and summarize the current knowledge on PPARγagonists from multiple clinical trials. Finally, we also review the new PPARγagonists under development as potential therapeutics with reduced or no adverse effects.

scholarly journals The Role of PPARγinHelicobacter pyloriInfection and Gastric Carcinogenesis

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Jong-Min Lee ◽  
Sung Soo Kim ◽  
Young-Seok Cho
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Current Knowledge ◽  
Mucosal Injury ◽  
Gastric Carcinogenesis ◽  
Etiologic Factor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
H Pylori

Peroxisome proliferator-activated receptorγ(PPARγ) is a nuclear receptor that is important in many physiological and pathological processes, such as lipid metabolism, insulin sensitivity, inflammation, cell proliferation, and carcinogenesis. Several studies have shown that PPARγplays an important role in gastric mucosal injury due toHelicobacter pylori(H. pylori). AsH. pyloriinfection is the main etiologic factor in chronic gastritis and gastric cancer, understanding of the potential roles of PPARγinH. pyloriinfection may lead to the development of a therapeutic target. In this paper, the authors discuss the current knowledge on the role of PPARγinH. pyloriinfection and its related gastric carcinogenesis.

scholarly journals Role of PPARαand Its Agonist in Renal Diseases

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Ching-Feng Cheng ◽  
Hsi-Hsien Chen ◽  
Heng Lin
Keyword(s):  
Kidney Diseases ◽  
Renal Diseases ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ligand Selectivity ◽  
Treatment Of Diabetes ◽  
Hypolipidemic Drugs ◽  
Anti Inflammation

Peroxisome proliferator-activated receptor (PPAR)-α, a member of a large nuclear receptor superfamily, plays a major role in the regulation of lipid metabolism. Recently, PPARαactivation has been shown to confer additional benefits on endothelial function, kidney function, and anti-inflammation, suggesting that PPARαagonists may be good candidates for treating acute renal failure. In clinical application, PPAR-αactivators, such as hypolipidemic drugs in fibric acid class, were proven to have therapeutic effects on metabolic syndrome and cardiovascular disease. This paper focuses on signaling pathways, ligand selectivity, and physio-pathological roles of PPARαin kidney diseases and the therapeutic utility of PPARαmodulators in the treatment of diabetes and inflammation-induced nephropathy. Implication of new and more potent PPAR-αactivators could provide important insights into the overall benefits of activating PPAR-αclinically for the treatment of dyslipidemia and the prevention of diabetic or inflammation-induced nephropathy in the future.

scholarly journals Gastrointestinal Cytoprotection by PPAR Ligands

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Yuji Naito ◽  
Tomohisa Takagi ◽  
Toshikazu Yoshikawa
Keyword(s):  
Immune Response ◽  
Cell Proliferation ◽  
Gastrointestinal Tract ◽  
Current Knowledge ◽  
Peroxisome Proliferator ◽  
Potential Therapeutic Target ◽  
Peroxisome Proliferator Activated Receptor ◽  
Gastrointestinal Inflammation ◽  
Ppar Ligands

Peroxisome proliferator-activated receptor (PPAR) is a nuclear receptor that is known to play a central role in lipid metabolism and insulin sensitivity as well as inflammation and cell proliferation. According to the results obtained from studies on several animal models of gastrointestinal inflammation, PPAR has been implicated in the regulation of the immune response, particularly inflammation control, and has gained importance as a potential therapeutic target in the management of gastrointestinal inflammation. In the present paper, we present the current knowledge on the role of PPAR ligands in the gastrointestinal tract.

scholarly journals Chemotherapy and Chemoprevention by Thiazolidinediones

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Eleonore Fröhlich ◽  
Richard Wahl
Keyword(s):  
Differentiated Thyroid Carcinoma ◽  
Dependent Data ◽  
Peroxisome Proliferator ◽  
Antitumor Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Diabetes Mellitus Type Ii ◽  
Cellular Targets ◽  
Treatment Of Diabetes ◽  
Expression Status

Thiazolidinediones (TZDs) are synthetic ligands of Peroxisome-Proliferator-Activated Receptor gamma (PPARγ). Troglitazone, rosiglitazone, and pioglitazone have been approved for treatment of diabetes mellitus type II. All three compounds, together with the first TZD ciglitazone, also showed an antitumor effect in preclinical studies and a beneficial effect in some clinical trials. This review summarizes hypotheses on the role of PPARγin tumors, on cellular targets of TZDs, antitumor effects of monotherapy and of TZDs in combination with other compounds, with a focus on their role in the treatment of differentiated thyroid carcinoma. The results of chemopreventive effects of TZDs are also considered. Existing data suggest that the action of TZDs is highly complex and that actions do not correlate with cellular PPARγexpression status. Effects are cell-, species-, and compound-specific and concentration-dependent. Data from human trials suggest the efficacy of TZDs as monotherapy in prostate cancer and glioma and as chemopreventive agent in colon, lung, and breast cancer. TZDs in combination with other therapies might increase antitumor effects in thyroid cancer, soft tissue sarcoma, and melanoma.

scholarly journals Review: Peroxisome Proliferator-Activated Receptor-γand Its Role in the Development and Treatment of Diabetes

2004 ◽  
Vol 5 (2) ◽  
pp. 99-109 ◽  
Author(s):  
Todd Leff ◽  
Suresh T. Mathews ◽  
Heidi S. Camp
Keyword(s):  
Adipocyte Differentiation ◽  
Basic Research ◽  
Current Status ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pharmaceutical Drug ◽  
Regulation Of Metabolism ◽  
Treatment Of Diabetes

Since its identification as the receptor for antidiabetic thiazolidinedione drugs, peroxisome proliferator-activated receptor-γ(PPARγ) has been the focus of pharmaceutical drug discovery programs directed toward finding better drugs for the treatment of diabetes, as well as the object of basic research aimed at understanding its role in the regulation of metabolism. We now understand a great deal about the crucial role that PPARγplays in adipocyte differentiation and development, and are rapidly gaining knowledge about the role of the receptor in the regulation of metabolism. However, many crucial aspects of the molecular mechanism by which modulation of PPARγactivity affects insulin resistance and glucose homeostasis are still not clearly understood. Here the authors review the current status of PPARγresearch, with an emphasis on its role in the causes and treatment of type 2 diabetes.

The Role of Adipokines in the Establishment and Progression of Head and Neck Neoplasms

2019 ◽  
Vol 26 (25) ◽  
pp. 4726-4748 ◽  
Author(s):  
Theodora Tzanavari ◽  
Jason Tasoulas ◽  
Chrysoula Vakaki ◽  
Chrysovalantou Mihailidou ◽  
Gerasimos Tsourouflis ◽  
...  
Keyword(s):  
Head And Neck ◽  
Current Knowledge ◽  
Prognostic Significance ◽  
Neck Region ◽  
Tumor Formation ◽  
Janus Kinase ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Head And Neck Region

Adipokines constitute a family of protein factors secreted by white adipose tissue (WAT), that regulate the functions of WAT and other sites. Leptin, adiponectin and resistin, are the main adipokines present in serum and saliva, targeting several tissues and organs, including vessels, muscles, liver and pancreas. Besides body mass regulation, adipokines affect glucose homeostasis, inflammation, angiogenesis, cell proliferation and apoptosis, and other crucial cell procedures. Their involvement in tumor formation and growth is well established and deregulation of adipokine and adipokine receptors’ expression is observed in several malignancies including those located in the head and neck region. Intracellular effects of adipokines are mediated by a plethora of receptors that activate several signaling cascades including Janus kinase/ Signal transducer and activator of transcription (JAK/ STAT pathway), Phospatidylinositol kinase (PI3/ Akt/ mTOR) and Peroxisome proliferator-activated receptor (PPAR). The present review summarizes the current knowledge on the role of adipokines family members in carcinogenesis of the head and neck region. The diagnostic and prognostic significance of adipokines and their potential role as serum and saliva biomarkers are also discussed.

scholarly journals The Role of Peroxisome Proliferator-Activated Receptors in the Esophageal, Gastric, and Colorectal Cancer

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Alessandra Fucci ◽  
Tommaso Colangelo ◽  
Carolina Votino ◽  
Massimo Pancione ◽  
Lina Sabatino ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Molecular Targets ◽  
Predictive Biomarkers ◽  
Cancer Development ◽  
Peroxisome Proliferator ◽  
Cellular Functions ◽  
Peroxisome Proliferator Activated Receptors

Tumors of the gastrointestinal tract are among the most frequent human malignancies and account for approximately 30% of cancer-related deaths worldwide. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that control diverse cellular functions such as proliferation, differentiation, and cell death. Owing to their involvement in so many processes, they play crucial roles also in the development and physiology of the gastrointestinal tract. Consistently, PPARs deregulation has been implicated in several pathophysiological conditions, including chronic inflammation and cancer development. This paper summarizes the current knowledge on the role that the various PPAR isoforms play in the pathogenesis of the esophageal, gastric, and intestinal cancer. Elucidation of the molecular mechanisms underlying PPARs' signaling pathways will provide insights into their possible use as predictive biomarkers in the initial stages of the process. In addition, this understanding will provide the basis for new molecular targets in cancer therapy and chemoprevention.

scholarly journals Emerging role of interleukin-1 in cardiovascular diseases

2009 ◽  
pp. 481-498
Author(s):  
B Vicenová ◽  
V Vopálenský ◽  
L Burýšek ◽  
M Pospíšek
Keyword(s):  
Rheumatoid Arthritis ◽  
Diabetes Mellitus ◽  
Cardiovascular Diseases ◽  
Cardiovascular Events ◽  
Current Knowledge ◽  
Interleukin 1 ◽  
Proinflammatory Mediators ◽  
Inflammatory Processes ◽  
Higher Eukaryotes

There is an increasing evidence linking dysbalance between various proinflammatory mediators and higher risk of cardiovascular events and pathologies. Likewise, some of the cardiovascular diseases lately appeared to have an autoimmune component. Interleukin-1 (IL-1), a master regulator of diverse inflammatory processes in higher eukaryotes and the key player in numerous autoimmune disorders including rheumatoid arthritis, diabetes mellitus or systemic sclerosis, has recently been proved to be involved in development of several cardiovascular diseases as well. This report aims to give a summary on current knowledge about the IL-1 signaling pathways and about the implication of IL-1 and the IL-1 receptor antagonist (IL-1Ra) in some of the diseases of the cardiovascular system.

scholarly journals Regulation of Cell Proliferation and Differentiation by PPARβ/δ

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-5 ◽  
Author(s):  
Rolf Müller ◽  
Markus Rieck ◽  
Sabine Müller-Brüsselbach
Keyword(s):  
Cell Proliferation ◽  
Current Knowledge ◽  
Cell Cycle Control ◽  
Peroxisome Proliferator ◽  
Oncogenic Signaling ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Oncogenic Signaling Pathways

Peroxisome proliferator-activated receptor-β/δ(PPARβ/δ) is a ligand-activated transcription factor with essential functions in the regulation of lipid catabolism, glucose homeostasis, and inflammation, which makes it a potentially relevant drug target for the treatment of major human diseases. In addition, there is strong evidence that PPARβ/δmodulates oncogenic signaling pathways and tumor growth. Consistent with these observations, numerous reports have clearly documented a role for PPARβ/δin cell cycle control, differentiation, and apoptosis. However, the precise role of PPARβ/δin tumorigenesis and cell proliferation remains controversial. This review summarizes our current knowledge and proposes a model corroborating the discrepant data in this area of research.

The emerging role of COX-2, 15-LOX, and PPARγ in metabolic diseases and cancer: An introduction to novel multi-target directed ligands (MTDLs)

2020 ◽  
Vol 27 ◽  
Author(s):  
Rana A. Alaaeddine ◽  
Perihan A. Elzahhar ◽  
Ibrahim AlZaim ◽  
Wassim Abou-Kheir ◽  
Ahmed S.F. Belal ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Biological Effects ◽  
Arachidonic Acid Metabolism ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cellular Targets ◽  
Design And Synthesis ◽  
Early Results ◽  
Cox 2

: Emerging evidence supports an intertwining framework for the involvement of different inflammatory pathways in a common pathological background for a number of disorders. Of importance are pathways involving arachidonic acid metabolism by cyclooxygenase-2 (COX-2) and 15-lipoxygenase (15-LOX). Both enzyme activities and their products are implicated in a range of pathophysiological processes encompassing metabolic impairment leading to adipose inflammation and the subsequent vascular and neurological disorders, in addition to various pro-and anti-tumorigenic effects. A further layer of complexity is encountered by the disparate, and often reciprocal, modulatory effect COX-2 and 15-LOX activities and metabolites exert on each other or on other cellular targets, the most prominent of which is peroxisome proliferator-activated receptor gamma (PPARγ). Thus, effective therapeutic intervention with such multifaceted disorders requires the simultaneous modulation of more than one target. Here, we describe the role of COX-2, 15-LOX, and PPARγ in cancer and complications of metabolic disorders, highlight the value of designing multi-target directed ligands (MTDLs) modifying their activity, and summarize the available literature regarding the rationale and feasibility of design and synthesis of these ligands together with their known biological effects. We speculate on the potential impact of MTDLs in these disorders as well as emphasize the need for structured future effort to translate these early results facilitating the adoption of these, and similar, molecules in clinical research.

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