Ellagic acid prevents monocrotaline-induced pulmonary artery hypertension via inhibiting NLRP3 inflammasome activation in rats

Tang, Bing; Chen, Guangxian; Liang, Mengya; Yao, Jianping; Wu, Zhongkai

doi:10.1016/j.ijcard.2014.11.161

Cited by 89 publications

(63 citation statements)

References 38 publications

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“…3a) and caspase-1 (we analysed the active subunit p20) (Fig. 3b) were upregulated in MCT-treated pneumonectomised rats compared with the sham group, which is inconsistent with previous findings showing NLRP3 inflammasome activation during lung inflammation under the pathologic condition of PH in rats [7]. In PH rats, both treatment and pretreatment with A-740003 efficiently abolished the upregulation of P2X 7 R and greatly decreased the increase in caspase-1 and IL-1β (Fig.…”

Section: Resultscontrasting

confidence: 94%

“…Drugs targeting the prostacyclin, endothelin-1 receptor, and phosphodiesterase pathways improve symptoms and exercise tolerance, but persistent morbidity and mortality indicate that important pathogenic mechanisms are minimally affected [5, 6]. There is accumulating evidence of a specific contribution of NLRP3 and related inflammasomes, and their regulated cytokines or receptors may represent novel diagnostic or therapeutic targets in pulmonary diseases, including PAH [7–9]. …”

Section: Introductionmentioning

confidence: 99%

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Role of P2X7R in the development and progression of pulmonary hypertension

et al. 2017

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BackgroundPulmonary arterial hypertension (PAH) is a devastating disease that lacks sufficient treatment. Studies have shown that the Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome contributes to PAH pathogenesis, but the role of the upstream molecular P2X7 receptor (P2X7R) has remained unexplored. We investigated the role of P2X7R in the pathogenesis of PAH.Methods and resultsPH was induced by a single subcutaneous injection of monocrotaline (MCT) (60 mg/kg) on left pneumonectomised Sprague-Dawley rats, as validated by significant increases in pulmonary artery pressure and vessel wall thickness. Marked P2X7R was detected by predominant PA immunostaining in lungs from PH rats. Western blot revealed a significant increase in the protein levels of P2X7R as well as NLRP3 and caspase-1 in the diseased lung tissue compared with normal tissue. The rats received A-740003 (a selective P2X7 receptor antagonist, 30 mg/kg) daily starting from 1 week before or 2 weeks after MCT injection. Consequently, A-740003 reversed the NLRP3 inflammasome upregulation, significantly decreased the mean right ventricular (RV) pressure and RV hypertrophy, and reversed pulmonary arterial remodelling 4 weeks after MCT injection, as both a pretreatment and rescue intervention. Notably, A-740003 significantly reduced macrophage and pro-inflammatory cytokine levels, as measured via bronchoalveolar lavage. The recruitment of macrophages as well as collagen fibre deposition in the perivascular areas were also reduced, as confirmed by histological staining.ConclusionsP2X7R contributes to the pathogenesis of PH, probably in association with activation of the NLRP3 inflammasome. Blockade of P2X7R might be applied as a novel therapeutic approach for the treatment of PAH.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-017-0603-0) contains supplementary material, which is available to authorized users.

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Section: Resultscontrasting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Role of P2X7R in the development and progression of pulmonary hypertension

et al. 2017

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“…One such polyphenol is ellagic acid (EA) which is found in berries, grapes, pomegranates, and nuts. It has received increasing attention in the scientific community due its potential as an anti-inflammatory [26,27] and antioxidant [28][29][30] compound. A recent study has demonstrated that EA lowered blood pressure in hypertensive rats via an antioxidant effect of EA which includes increased nitric oxide synthase (NOS) expression and decreased ROS levels in the plasma [28].…”

Section: Introductionmentioning

confidence: 99%

Ellagic Acid Reduces High Glucose-Induced Vascular Oxidative Stress Through ERK1/2/NOX4 Signaling Pathway

Rozentsvit

Vinokur

Samuel

et al. 2017

Cell Physiol Biochem

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Background/Aims: Elevated production of reactive oxygen species (ROS) is linked to endothelial dysfunction and is one of the key contributors to the pathogenesis of diabetic vascular complications. Emerging evidence has indicated that ellagic acid (EA), a polyphenol found in fruits and nuts, possesses numerous biological activities including radical scavenging. However, whether EA exerts a vasculo-protective effect via antioxidant mechanisms in blood vessels exposed to diabetic conditions remains unknown. Accordingly, the goal of this current study was to determine whether EA decreases vascular ROS production and thus ameliorates endothelial dysfunction in the diabetic milieu. Methods: Intact rat aortas and human aortic endothelial cells (HAEC) were stimulated with 30mM high glucose (HG) with and without EA co-treatment. Endothelium-dependent vasodilation was measured using a wire myograph. Gene and protein expression of non-phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 4 (NOX4) were detected using RT-PCR and western blotting, respectively. Oxidative stress was determined by measuring ROS levels using dihydroethidium (DHE) staining. Results: Intact aortas exposed to HG condition displayed exacerbated ROS production and impairment of endothelium-dependent vasodilation, characterizing endothelial dysfunction. These effects were markedly reduced with EA treatment. HG enhanced ROS production in HAEC, paralleled by increased ERK1/2 activation and NOX4 expression. EA treatment blunted the increase of ROS generation, ERK1/2 activation and decreased NOX4. Conclusions: EA significantly decreases endothelial ROS levels and ameliorates the impairment of vascular relaxation induced by HG. Our results suggest that EA exerts a vasculo-protective effect under diabetic conditions via an antioxidant effect that involves inhibition of ERK1/2 and downregulation of NOX4.

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“…Based on the activation mode of NLRP3, inhibiting NLRP3 inflammasome activation may have beneficial effects in preventing the damage mediated by the sterile inflammatory response in cardiovascular diseases such as CHD and MI. Preventing pathological NLRP3 inflammasome from activation may provide some insight into the future prevention and treatment of cardiovascular diseases [1,3,10]. Currently, the most promising treatments for inhibiting NLRP3 are anti-IL-1, inhibition of caspase-1, and P2X7 receptors antagonist [47][48][49].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, inflammasome is likely to control the inflammation in the development of cardiovascular diseases [6][7][8]. NLRP3 inflammasome, the most typically inflamma-some which could be activated by crystal or particle pathogen damage-associated molecular patterns (PAMPs) and ischemic hypoxia danger-associated molecular patterns (DAMPs), can promote the secretion of IL-1β and IL-18 [9][10][11]. Through these mechanisms, it promotes atherosclerosis (AS), coronary heart diseases (CHD), heart ischemia-reperfusion (I/R) injury, and so on [12].…”

Section: Introductionmentioning

confidence: 99%

NLRP3 Inflammasome and Its Central Role in the Cardiovascular Diseases

Tong

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Background/Aims. NLRP3 inflammasome, an inflammasome which consists of nucleotide-binding oligomerization domain- (Nod-) like receptor3 (NLRP3) scaffold, apoptosis-associated speck-like protein (ASC) containing a CARD adaptor, and pro-caspase-1, is assembled after the cytoplasmic leucine-rich repeats (LRRs) of NLRP3 sense pathogens or danger signals. In recent years, the role of inflammasome in cardiovascular diseases has attracted mounting attention, and the in-depth study of its mechanism is gradually clear. Materials. The NLRP3 inflammasome controls the activation of the proteolytic enzyme caspase-1. Caspase-1 in turn regulates the maturation of the proinflammasome cytokines IL-1β and IL-18, which leads to an inflammatory response. We made a mini-review on the association of regulatory mechanisms of NLRP3 inflammasome with the development of cardiovascular diseases systematically based on the recent research studies. Discussion. The inflammasome plays an indispensable role in the development of atherosclerosis, coronary heart diseases (CHD), and heart ischemia-reperfusion (I/R) injury, and NLRP3 inflammasome may become a new target for the prevention and treatment of cardiovascular diseases. Effective regulation of NLRP3 may help prevent or even treat cardiovascular diseases. Conclusion. This mini-review focuses on the association of regulatory mechanisms of NLRP3 inflammasome with the development of cardiovascular diseases, which may supply some important clues for future therapies and novel drug targets for cardiovascular diseases.

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Ellagic acid prevents monocrotaline-induced pulmonary artery hypertension via inhibiting NLRP3 inflammasome activation in rats

Abstract: Ellagic acid ameliorates monocrotaline-induced pulmonary artery hypertension via exerting its anti-oxidative property inhibiting NLRP3 inflammasome signal pathway in rats.

Cited by 89 publications

References 38 publications

Role of P2X7R in the development and progression of pulmonary hypertension

Role of P2X7R in the development and progression of pulmonary hypertension

Ellagic Acid Reduces High Glucose-Induced Vascular Oxidative Stress Through ERK1/2/NOX4 Signaling Pathway

NLRP3 Inflammasome and Its Central Role in the Cardiovascular Diseases

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