Comparison of PPARδ and PPARγ in inhibiting the pro-inflammatory effects of C-reactive protein in endothelial cells

Liang, Yao Jen; Liu, Yuan Chun; Chen, Chao Yi; Lai, Ling‐Ping; Shyu, Kou Gi; Juang, Shiow Jen; Wang, Bao Wei; Leu, Jyh Gang

doi:10.1016/j.ijcard.2009.03.100

Cited by 24 publications

(15 citation statements)

References 27 publications

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“…Interestingly, these changes occur independently of improvements in dyslipidemia, glycemic control and hypertension [150,200], which support direct vascular effects. In addition, it is shown that LDL-R-null mice transplanted with PPARγ-deficient bone marrow developed more severe atherosclerosis as compared with mice transplanted with bone marrow from control animals [146], further confirming the antiatherosclerotic actions of PPARγ.…”

Section: Pparsmentioning

confidence: 91%

“…By contrast, selective PPARδ agonists effectively suppress VSMC proliferation both under basal condition [148], and in response to TNF-α [54,71]. Likewise, PPARδ agonist L-16501 interferes with neointima formation in the carotid-artery balloon injury model [146]. In addition, it has been demonstrated that PPARδ ligand inhibits VSMC proliferation via simultaneous induction of TGF-β1 and inhibition of MCP-1 and IL-1β production [118,149].…”

Section: Pparsmentioning

confidence: 99%

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Peroxisome proliferator-activated receptors, Metabolic Syndrome and Cardiovascular Disease

Azhar

2010

Future Cardiol.

124

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Metabolic syndrome (MetS) is a constellation of risk factors including insulin resistance, central obesity, dyslipidemia and hypertension that markedly increase the risk of Type 2 diabetes (T2DM) and cardiovascular disease (CVD). The peroxisome proliferators-activated receptor (PPAR) isotypes, PPARα, PPARδ/β and PPARγ are ligand-activated nuclear transcription factors, which modulate the expression of an array of genes that play a central role in regulating glucose, lipid and cholesterol metabolism, where imbalance can lead to obesity, T2DM and CVD. They are also drug targets, and currently, PPARα (fibrates) and PPARγ (thiazolodinediones) agonists are in clinical use for treating dyslipidemia and T2DM, respectively. These metabolic characteristics of the PPARs, coupled with their involvement in metabolic diseases, mean extensive efforts are underway worldwide to develop new and efficacious PPAR-based therapies for the treatment of additional maladies associated with the MetS. This article presents an overview of the functional characteristics of three PPAR isotypes, discusses recent advances in our understanding of the diverse biological actions of PPARs, particularly in the vascular system, and summarizes the developmental status of new single, dual, pan (multiple) and partial PPAR agonists for the clinical management of key components of MetS, T2DM and CVD. It also summarizes the clinical outcomes from various clinical trials aimed at evaluating the atheroprotective actions of currently used fibrates and thiazolodinediones.

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Section: Pparsmentioning

confidence: 91%

Section: Pparsmentioning

confidence: 99%

Peroxisome proliferator-activated receptors, Metabolic Syndrome and Cardiovascular Disease

Azhar

2010

Future Cardiol.

124

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“…Supporting this statement, treatment of primary vascular endothelial EAhy926 cells with the Merck ligand PPAR β / δ activator L-165041 suppressed TNF α -induced adhesion molecule (such as VCAM-1 and MCP-1) through significant reduction in the nuclear translocation of NF- κ B [216, 217]. Furthermore, treating human umbilical vein endothelial cells (HUVEC) with the same molecule reduced the levels of C-reactive protein-mediated increase of Interleukin-6 (IL-6) and IL-8 [218]. Using the selective PPAR β / δ agonist GW501516, others also reported the critical role of PPAR β / δ in the suppression of IL-1 β -induced VCAM-1 and E-selectin expression in HUVECs [219].…”

Section: Ppars Inflammation and Endotheliummentioning

confidence: 99%

Nuclear Control of the Inflammatory Response in Mammals by Peroxisome Proliferator-Activated Receptors

Mandard

Patsouris

2013

PPAR Research

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Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that play pivotal roles in the regulation of a very large number of biological processes including inflammation. Using specific examples, this paper focuses on the interplay between PPARs and innate immunity/inflammation and, when possible, compares it among species. We focus on recent discoveries establishing how inflammation and PPARs interact in the context of obesity-induced inflammation and type 2 diabetes, mostly in mouse and humans. We illustrate that PPARγ ability to alleviate obesity-associated inflammation raises an interesting pharmacologic potential. In the light of recent findings, the protective role of PPARα and PPARβ/δ against the hepatic inflammatory response is also addressed. While PPARs agonists are well-established agents that can treat numerous inflammatory issues in rodents and humans, surprisingly very little has been described in other species. We therefore also review the implication of PPARs in inflammatory bowel disease; acute-phase response; and central, cardiac, and endothelial inflammation and compare it along different species (mainly mouse, rat, human, and pig). In the light of the data available in the literature, there is no doubt that more studies concerning the impact of PPAR ligands in livestock should be undertaken because it may finally raise unconsidered health and sanitary benefits.

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“…More directly, PPARβ/δ activation by GW501516 antagonizes inflammation by inducing expression of sIL-1ra [61] and transforming growth factor-β1 (TGF-β1) [62]. Like PPARα- and PPARγ-activating ligands, PPARβ/δ agonists suppress endothelial cells’ expression of adhesion molecules such as VCAM-1, ICAM-1, and E-selectin that are required for leukocyte recruitment [63–66] as well as the chemokines MCP-1 and growth-regulated oncogene-α (GROα) [63, 65, 66]. …”

Section: Roles Of Ppars In Asthmamentioning

confidence: 99%

PPARs: Key Regulators of Airway Inflammation and Potential Therapeutic Targets in Asthma

Banno

Reddy

Lakshmi

et al. 2018

Nuclear Receptor Research

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Asthma affects approximately 300 million people worldwide, significantly impacting quality of life and healthcare costs. While current therapies are effective in controlling many patients’ symptoms, a large number continue to experience exacerbations or treatment-related adverse effects. Alternative therapies are thus urgently needed. Accumulating evidence has shown that the peroxisome proliferator-activated receptor (PPAR) family of nuclear hormone receptors, comprising PPARα, PPARβ/δ, and PPARγ, is involved in asthma pathogenesis and that ligand-induced activation of these receptors suppresses asthma pathology. PPAR agonists exert their anti-inflammatory effects primarily by suppressing pro-inflammatory mediators and antagonizing the pro-inflammatory functions of various cell types relevant to asthma pathophysiology. Experimental findings strongly support the potential clinical benefits of PPAR agonists in the treatment of asthma. We review current literature, highlighting PPARs’ key role in asthma pathogenesis and their agonists’ therapeutic potential. With additional research and rigorous clinical studies, PPARs may become attractive therapeutic targets in this disease.

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Comparison of PPARδ and PPARγ in inhibiting the pro-inflammatory effects of C-reactive protein in endothelial cells

Cited by 24 publications

References 27 publications

Peroxisome proliferator-activated receptors, Metabolic Syndrome and Cardiovascular Disease

Peroxisome proliferator-activated receptors, Metabolic Syndrome and Cardiovascular Disease

Nuclear Control of the Inflammatory Response in Mammals by Peroxisome Proliferator-Activated Receptors

PPARs: Key Regulators of Airway Inflammation and Potential Therapeutic Targets in Asthma

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