CPU0213, a novel endothelin type A and type B receptor antagonist, protects against myocardial ischemia/reperfusion injury in rats

Wang, Z.Y.; Zhang, W.; Li, X.Z.; Han, Yi; Chen, Y.P.; Liu, Z.; Xie, Liping; Ji, Yong; Xu, Lei

doi:10.1590/s0100-879x2011007500119

Cited by 3 publications

(4 citation statements)

References 37 publications

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“…Vascular regulatory factors secreted by vascular endothelial cells play an important role in the formation of thrombus, and ET and NO play an important role in regulating contraction and relaxation of blood vessels and the formation of thrombosis (45). ET has a strong role in promoting endothelial cell proliferation and blood vessels contraction, and can also induce myocardial ischemia and remodeling by promoting vascular smooth muscle cell activation and proliferation (6,46). NO has the effect of relaxing vascular smooth muscle, and inhibiting thrombus formation and endothelial cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…During myocardial IR, endothelial cells not only produce large amounts of reactive oxygen species (ROS) but also significantly reduce antioxidant activity. The production of endothelin (ET) after myocardial IR is increased, thereby resulting in the strong contraction of blood vessels and a large accumulation of platelets which aggravate cardiomyocyte damage (6,7).…”

Section: Introductionmentioning

confidence: 99%

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Shuxuening injection protects against myocardial ischemia-reperfusion injury through reducing oxidative stress, inflammation and thrombosis

Wang¹,

Wang²,

Zhou³

et al. 2019

Ann. Transl. Med.

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Background: Shuxuening injection (SXNI) has a good effect on cardiovascular and cerebrovascular diseases. Here, our study aims to investigate whether SXNI have the protective effect on myocardial ischemia-reperfusion injury (MIRI) and elucidate the mechanism of SXNI's cardiac protection. Methods:In this experiment, the coronary arteries of Sprague-Dawley (SD) rats were ligated for the induction of a MIRI model. TTC staining and haematoxylin-eosin (HE), as well as troponin I (TnI), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatine kinase (CK) and CK-MB levels, were used to detect the protective effect of SXNI. In rat cardiac tissue, superoxide dismutase, catalase, glutathione and malondialdehyde (MDA) activities and glucose-regulated protein 78 (GRP78), calreticulin (CRT), CCAAT/ enhancer binding protein homologous protein (CHOP) and caspase-12 expression levels were detected.In rat serum, the levels of inflammatory factors, including high-sensitivity C-reactive protein, monocyte chemoattractant protein-1, tumour necrosis factor-α, interleukin-6 (IL-6) and IL-1β, were measured by Elisa. In the rat arterial tissue, Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) expression was measured by western blot. In the rat plasma, ELISA was used to assay the levels of coagulation and plasmin system indicators, including platelet activating factor, endothelin, tissue factor (TF), plasminogen inhibitor, thromboxane B2, plasma fibrinogen. Results:The results showed that SXNI can reduce the infarct size of myocardial tissue, decrease the myocardial enzyme and TnI levels and decrease the degree of myocardial damage compared with the model group. Additionally, SXNI can increase the activity of antioxidant enzymes, reduce the MDA level and decrease the GRP78, CRT, CHOP and caspase-12 expression levels. SXNI also decreased the levels of inflammatory cytokines in rat serum, lowered the level of procoagulant molecules in plasma and reduced the TLR4/NF-κB expression.Conclusions: SXNI has protective effect on MIRI mainly by inhibiting oxidative stress and endoplasmic reticulum stress (ERS), thereby regulating TLR4/NF-κB pathway to reduce inflammation, and lowing procoagulant-related factors levels to reduce the risk of thrombosis. Wang et al. SXNI protects against myocardial ischemia-reperfusion injury

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Shuxuening injection protects against myocardial ischemia-reperfusion injury through reducing oxidative stress, inflammation and thrombosis

Wang¹,

Wang²,

Zhou³

et al. 2019

Ann. Transl. Med.

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“…Three known isoforms of ET (ET-1, ET-2 and ET-3) have been identified, amongst which ET-1 is considered to be the isoform of greatest importance in the cardiovascular system [4]. ET-1 may play a pathophysiological role during development of AS, since it has been shown to cause myocardial hypertrophy [5], interstitial fibrosis [6] and fibroblast proliferation [7].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, blockage of ET-1 receptors protects against the deleterious effects of ET-1 [4]. ET-1 release from the myocardium may therefore be involved both in I/R injury during AVR and in the remodeling/reverse remodeling process associated with AS and AVR.…”

Section: Introductionmentioning

confidence: 99%

Endothelin-1 in the Human Myocardium and Circulating Plasma: Evaluation before, during and after Correction of Aortic Stenosis with Aortic Valve Replacement

Majak¹,

Bjørnstad²,

Braathen³

et al. 2012

Cardiology

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Objectives: Due to the pathological effects of endothelin-1 (ET-1) on cardiomyocytes and the extracellular matrix, ET-1 levels may impact on the prognosis of aortic stenosis (AS) patients operated with aortic valve replacement (AVR). We examined ET-1 levels in AS patients throughout the whole AVR process, thus exposing potential therapeutic windows of opportunity. Methods: Plasma ET-1 levels were measured before and 2 days, 6 and 12 months after AVR in 22 patients with AS. Myocardial ET-1 was measured in biopsies from 7 patients undergoing AVR. Peroperatively, plasma ET-1 was analyzed in the coronary sinus and radial artery before aortic cross-clamp and at 5 and 20 min of reperfusion, in a second group of 30 patients. Results: Circulating ET-1 levels were transiently increased 2.6-fold 2 days following AVR. Myocardial ET-1 protein was 2.1-fold higher in patients with AS compared to controls. Plasma levels of ET-1 correlated to echocardiographic markers of diastolic dysfunction postoperatively. There was no increase in plasma ET-1 during early reperfusion, but veno-arterial differences indicated potential cardiac ET-1 extraction. Conclusions: Plasma ET-1 increases 2 days following AVR and myocardial ET-1 protein levels are increased in patients with AS before AVR. Peroperatively, no plasma ET-1 augmentation or release from the heart was observed in AS patients.

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Endothelin in Coronary Artery Disease and Myocardial Infarction

Kolettis

Barton

Langleben

et al. 2013

Cardiology in Review

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Coronary artery disease remains a major cause of morbidity and mortality. Experimental and clinical data have indicated an important role of endothelin-1 at various subclinical and clinical stages of the disease. Endothelin-1 causes endothelial dysfunction and inflammation and may contribute to atherosclerotic plaque formation. During acute myocardial infarction, endothelin-1 enhances myocardial necrosis and arrhythmogenesis, but seems to exert a favorable effect on subsequent infarct healing and early ventricular remodeling. In the chronic postinfarction phase, endothelin-1 increases left ventricular afterload and participates in the myocardial fibrotic process. The progressive understanding of these actions has stimulated a large number of experimental and clinical studies examining the various effects of endothelin receptor blockade in coronary artery disease and chronic heart failure. However, this research has yielded largely contradictory results that have stirred scientific debates and controversies. This review summarizes the current state-of-the-art on this exciting topic, focusing on potential clinical ramifications.

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CPU0213, a novel endothelin type A and type B receptor antagonist, protects against myocardial ischemia/reperfusion injury in rats

Cited by 3 publications

References 37 publications

Shuxuening injection protects against myocardial ischemia-reperfusion injury through reducing oxidative stress, inflammation and thrombosis

Shuxuening injection protects against myocardial ischemia-reperfusion injury through reducing oxidative stress, inflammation and thrombosis

Endothelin-1 in the Human Myocardium and Circulating Plasma: Evaluation before, during and after Correction of Aortic Stenosis with Aortic Valve Replacement

Endothelin in Coronary Artery Disease and Myocardial Infarction

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