Atorvastatin inhibits pyroptosis through the lncRNA NEXN-AS1/NEXN pathway in human vascular endothelial cells

Wu, Limei; Wu, Shao-Guo; Chen, Fei; Qian, Wei; Wu, Chang-Meng; Kang, Chun‐Min; He, Xin; Zhang, Ruyi; Lu, Zhifeng; Li, Xue-Heng; Xu, Yuzhong; Liu, Limin; Li, Ding; Bai, Huan-Lan; Li, Xuehui; Hu, Yan‐Wei; Zheng, Lei

doi:10.1016/j.atherosclerosis.2019.11.033

Cited by 65 publications

(50 citation statements)

References 42 publications

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“…indicate that cerebral ischemia/reperfusion is involved in the canonical non-infectious pathway of pyroptosis in multiple cell types, including vascular endothelial cells, neurons, and astrocytes involves the canonical noninfectious pathway of pyroptosis [31][32][33]. However, to date, it is not known whether co-culturing OM-MSCs with microglia has a protective effect against either pyroptotic or apoptotic cell death during cerebral I/R injury.…”

Section: Agingmentioning

confidence: 99%

Hypoxia-preconditioned olfactory mucosa mesenchymal stem cells abolish cerebral ischemia/reperfusion-induced pyroptosis and apoptotic death of microglial cells by activating HIF-1α

Huang

Tan

Zhuo

et al. 2020

Aging

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Among central nervous system (CNS) diseases, cerebral ischemic stroke is the most common cause of death and disability [1]. This condition has been successfully treated with tissue plasminogen activator (tPA) therapy. However, the reperfusion process may result in serious brain tissue damage [2], and has been an intractable challenge in stroke treatment. It is, therefore, crucial to elucidate the latent mechanisms of cerebral I/R injury. Cerebral I/R insult is often accompanied with inflammation [3]. In addition, cerebral I/R injury causes different subtypes of programmed cell death, including

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Section: Agingmentioning

confidence: 99%

Hypoxia-preconditioned olfactory mucosa mesenchymal stem cells abolish cerebral ischemia/reperfusion-induced pyroptosis and apoptotic death of microglial cells by activating HIF-1α

Huang

Tan

Zhuo

et al. 2020

Aging

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“…Pyroptosis-induced inflammation is involved in the development of human inflammatory diseases. Atorvastatin decreases expression of NLRP3, caspase1, GSDMD and inflammatory factors (IL-1β and IL-18) via the lncRNA nexilin F-actin binding protein antisense RNA 1 (NEXN-AS1)/NEXN pathway to inhibit human vascular endothelial cell pyroptosis, reversing atherosclerosis [56].…”

Section: Non-coding Rna-regulated Pyroptosis Impacts On Inflammatory mentioning

confidence: 99%

Mechanisms and Therapeutic Regulation of Pyroptosis in Inflammatory Diseases and Cancer

Zheng

2020

IJMS

139

111

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Programmed Cell Death (PCD) is considered to be a pathological form of cell death when mediated by an intracellular program and it balances cell death with survival of normal cells. Pyroptosis, a type of PCD, is induced by the inflammatory caspase cleavage of gasdermin D (GSDMD) and apoptotic caspase cleavage of gasdermin E (GSDME). This review aims to summarize the latest molecular mechanisms about pyroptosis mediated by pore-forming GSDMD and GSDME proteins that permeabilize plasma and mitochondrial membrane activating pyroptosis and apoptosis. We also discuss the potentiality of pyroptosis as a therapeutic target in human diseases. Blockade of pyroptosis by compounds can treat inflammatory disease and pyroptosis activation contributes to cancer therapy.

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“…Beyond lowering cholesterol, statins have been associated with a range of beneficial pleiotropic effects including anti-inflammatory, antioxidant and immunomodulatory effects, inhibition of platelet activation, regulation of pyroptosis, and increased plaque stability [12][13][14]. For example, statins mediate a dose-dependent decrease in C-reactive protein [15], may impact renal function [16,17], and attenuate postpartum cardiovascular dysfunction in a rat preeclampsia model [18].…”

Section: Introductionmentioning

confidence: 99%

Statin-Related Myotoxicity: A Comprehensive Review of Pharmacokinetic, Pharmacogenomic and Muscle Components

Turner

Pirmohamed

2019

JCM

142

126

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Statins are a cornerstone in the pharmacological prevention of cardiovascular disease. Although generally well tolerated, a small subset of patients experience statin-related myotoxicity (SRM). SRM is heterogeneous in presentation; phenotypes include the relatively more common myalgias, infrequent myopathies, and rare rhabdomyolysis. Very rarely, statins induce an anti-HMGCR positive immune-mediated necrotizing myopathy. Diagnosing SRM in clinical practice can be challenging, particularly for mild SRM that is frequently due to alternative aetiologies and the nocebo effect. Nevertheless, SRM can directly harm patients and lead to statin discontinuation/non-adherence, which increases the risk of cardiovascular events. Several factors increase systemic statin exposure and predispose to SRM, including advanced age, concomitant medications, and the nonsynonymous variant, rs4149056, in SLCO1B1, which encodes the hepatic sinusoidal transporter, OATP1B1. Increased exposure of skeletal muscle to statins increases the risk of mitochondrial dysfunction, calcium signalling disruption, reduced prenylation, atrogin-1 mediated atrophy and pro-apoptotic signalling. Rare variants in several metabolic myopathy genes including CACNA1S, CPT2, LPIN1, PYGM and RYR1 increase myopathy/rhabdomyolysis risk following statin exposure. The immune system is implicated in both conventional statin intolerance/myotoxicity via LILRB5 rs12975366, and a strong association exists between HLA-DRB1*11:01 and anti-HMGCR positive myopathy. Epigenetic factors (miR-499-5p, miR-145) have also been implicated in statin myotoxicity. SRM remains a challenge to the safe and effective use of statins, although consensus strategies to manage SRM have been proposed. Further research is required, including stringent phenotyping of mild SRM through N-of-1 trials coupled to systems pharmacology omics- approaches to identify novel risk factors and provide mechanistic insight.

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Atorvastatin inhibits pyroptosis through the lncRNA NEXN-AS1/NEXN pathway in human vascular endothelial cells

Cited by 65 publications

References 42 publications

Hypoxia-preconditioned olfactory mucosa mesenchymal stem cells abolish cerebral ischemia/reperfusion-induced pyroptosis and apoptotic death of microglial cells by activating HIF-1α

Hypoxia-preconditioned olfactory mucosa mesenchymal stem cells abolish cerebral ischemia/reperfusion-induced pyroptosis and apoptotic death of microglial cells by activating HIF-1α

Mechanisms and Therapeutic Regulation of Pyroptosis in Inflammatory Diseases and Cancer

Statin-Related Myotoxicity: A Comprehensive Review of Pharmacokinetic, Pharmacogenomic and Muscle Components

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