Vascular smooth muscle cell peroxisome proliferator-activated receptor γ protects against endothelin-1-induced oxidative stress and inflammation

Idris‐Khodja, Noureddine; Ouerd, Sofiane; Trindade, Michelle; Gornitsky, Jordan; Rehman, Asia; Barhoumi, Tlili; Offermanns, Stefan; Gonzalez, Frank J.; Neves, Mário Fritsch; Paradis, Pierre; Schiffrin, Ernesto L.

doi:10.1097/hjh.0000000000001324

Cited by 33 publications

(30 citation statements)

References 45 publications

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“…Important antioxidant enzymes including heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2)/are regulated through the PPARγ pathway [147]. The inactivation of PPARγ exaggerates ET-1-induced vascular injury, suggesting a protective role of PPARγ in cardiovascular diseases through the modulation of pro-oxidant and proinflammatory pathways [148]. In a rat model of obesity and metabolic syndrome, treatment with the PPARγ agonist (rosiglitazone) increases insulin sensitivity, reduces fasting insulin levels and triglyceride concentration, increases CSE expression and activity as well as PVAT H 2 S production, and is associated with improvements in the anticontractile effect of PVAT on aortic rings [149].…”

Section: Pparγ and Pgc-1αmentioning

confidence: 99%

Perivascular Adipose Tissue as a Target for Antioxidant Therapy for Cardiovascular Complications

et al. 2020

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Perivascular adipose tissue (PVAT) is the connective tissue surrounding most of the systemic blood vessels. PVAT is now recognized as an important endocrine tissue that maintains vascular homeostasis. Healthy PVAT has anticontractile, anti-inflammatory, and antioxidative roles. Vascular oxidative stress is an important pathophysiological event in cardiometabolic complications of obesity, type 2 diabetes, and hypertension. Accumulating data from both humans and experimental animal models suggests that PVAT dysfunction is potentially linked to cardiovascular diseases, and associated with augmented vascular inflammation, oxidative stress, and arterial remodeling. Reactive oxygen species produced from PVAT can be originated from mitochondria, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, and uncoupled endothelial nitric oxide synthase. PVAT can also sense vascular paracrine signals and response by secreting vasoactive adipokines. Therefore, PVAT may constitute a novel therapeutic target for the prevention and treatment of cardiovascular diseases. In this review, we summarize recent findings on PVAT functions, ROS production, and oxidative stress in different pathophysiological settings and discuss the potential antioxidant therapies for cardiovascular diseases by targeting PVAT.

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Section: Pparγ and Pgc-1αmentioning

confidence: 99%

Perivascular Adipose Tissue as a Target for Antioxidant Therapy for Cardiovascular Complications

et al. 2020

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“…Moreover, ROS production can result from the decrease of peroxisome proliferator-activated receptor-γ (PPAR-γ), which protects against oxidative stress and inflammation by inhibiting monocyte chemoattractant protein-1 (MCP-1) and NADPH oxidase (Nox)-4. 55,56 Nox has been reported to be a major source of hydrogen superoxide in the vasculature, contributing to EC dysfunction and PASMC proliferation. Hydrogen superoxide reacts with nitric oxide (NO) to form the ROS peroxynitrite.…”

Section: Factors Involved In Ec Dysfunctionmentioning

confidence: 99%

Pulmonary hypertension secondary to congenital diaphragmatic hernia: factors and pathways involved in pulmonary vascular remodeling

2019

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Congenital diaphragmatic hernia (CDH) is a severe birth defect that is characterized by pulmonary hypoplasia and pulmonary hypertension (PHTN). PHTN secondary to CDH is a result of vascular remodeling, a structural alteration in the pulmonary vessel wall that occurs in the fetus. Factors involved in vascular remodeling have been reported in several studies, but their interactions remain unclear. To help understand PHTN pathophysiology and design novel preventative and treatment strategies, we have conducted a systematic review of the literature and comprehensively analyzed all factors and pathways involved in the pathogenesis of pulmonary vascular remodeling secondary to CDH in the nitrofen model. Moreover, we have linked the dysregulated factors with pathways involved in human CDH. Of the 358 full-text articles screened, 75 studies reported factors that play a critical role in vascular remodeling secondary to CDH. Overall, the impairment of epithelial homeostasis present in pulmonary hypoplasia results in altered signaling to endothelial cells, leading to endothelial dysfunction. This causes an impairment of the crosstalk between endothelial cells and pulmonary artery smooth muscle cells, resulting in increased smooth muscle cell proliferation, resistance to apoptosis, and vasoconstriction, which clinically translate into PHTN.

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“…Additionally, we and others have described that pioglitazone reduces ET-1 production, which might also contribute to its cardioprotective properties 5,31,32,49 . Furthermore, PPARγ regulates ET-1 activated processes such as vasoconstriction 50 and cardiac hypertrophy 51,52 and a recent report suggests that specific VSMC PPARγ counteracts ET-1-induced vascular damage 6 . Among the mechanisms responsible for these effects, earlier studies demonstrated that rosiglitazone reduces the contraction to ET-1 by reducing ET A and increasing ET B expression 53,54 , probably due to the fact that ET B gene is a direct target of the transcription factor PPARγ 53 .…”

Section: Discussionmentioning

confidence: 99%

“…PPARγ is expressed in all vascular cells, including vascular smooth muscle cells (VSMC) 2 . PPARγ activation reduces reactive oxygen species (ROS) production and inflammatory molecules such as cyclooxygenase-2 (COX-2) by interfering with mitogen-activated protein kinases (MAPK) and/or proinflammatory transcription factors 3–6 , explaining the cardioprotective effect of PPARγ agonists 7 . In this sense, PPARγ ligands antagonize the vascular damage and functional alterations observed in inflammatory pathologies such as hypertension 8–10 .…”

Section: Introductionmentioning

confidence: 99%

Pioglitazone Modulates the Vascular Contractility in Hypertension by Interference with ET-1 Pathway

Palacios

Hernanz

Martin

et al. 2019

Sci Rep

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Endothelin-1 (ET-1) is an important modulator of the vascular tone and a proinflammatory molecule that contributes to the vascular damage observed in hypertension. Peroxisome-proliferator activated receptors-γ (PPARγ) agonists show cardioprotective properties by decreasing inflammatory molecules such as COX-2 and reactive oxygen species (ROS), among others. We investigated the possible modulatory effect of PPARγ activation on the vascular effects of ET-1 in hypertension. In spontaneously hypertensive rats (SHR), but not in normotensive rats, ET-1 enhanced phenylephrine-induced contraction through ETA by a mechanism dependent on activation of TP receptors by COX-2-derived prostacyclin and reduction in NO bioavailability due to enhanced ROS production. In SHR, the PPARγ agonist pioglitazone (2.5 mg/Kg·day, 28 days) reduced the increased ETA levels and increased those of ETB. After pioglitazone treatment of SHR, ET-1 through ETB decreased ROS levels that resulted in increased NO bioavailability and diminished phenylephrine contraction. In vascular smooth muscle cells from SHR, ET-1 increased ROS production through AP-1 and NFκB activation, leading to enhanced COX-2 expression. These effects were blocked by pioglitazone. In summary, in hypertension, pioglitazone shifts the vascular ETA/ETB ratio, reduces ROS/COX-2 activation and increases NO availability; these changes explain the effect of ET-1 decreasing phenylephrine-induced contraction.

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Vascular smooth muscle cell peroxisome proliferator-activated receptor γ protects against endothelin-1-induced oxidative stress and inflammation

Cited by 33 publications

References 45 publications

Perivascular Adipose Tissue as a Target for Antioxidant Therapy for Cardiovascular Complications

Perivascular Adipose Tissue as a Target for Antioxidant Therapy for Cardiovascular Complications

Pulmonary hypertension secondary to congenital diaphragmatic hernia: factors and pathways involved in pulmonary vascular remodeling

Pioglitazone Modulates the Vascular Contractility in Hypertension by Interference with ET-1 Pathway

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