Knockdown of circHECTD1 inhibits oxygen-glucose deprivation and reperfusion induced endothelial-mesenchymal transition

He, Guohua; Wang, Zhen; Xu, Wei; Song, Kangping; Xi, Hui

doi:10.1007/s11011-021-00891-5

Cited by 9 publications

(5 citation statements)

References 48 publications

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“…Although EndoMT mainly occurs during embryonic development and was described for the first time during the differentiation of endocardium cells during the morphogenesis of the heart cushion. EndoMT also participates in the wound healing and inflammation process in adult organisms, contributing to the development of various cardiovascular diseases, including atherosclerosis and stroke [22–24]. This experimental evidence suggests that EndoMT may be a therapeutic target for treating vascular-related lesions.…”

Section: Discussionmentioning

confidence: 99%

NDUFC2 deficiency exacerbates endothelial mesenchymal transformation during ischemia-reperfusion via NLRP3

Chen¹,

Liu²,

Bi³

et al. 2023

NeuroReport

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Ischemic stroke is the main type of cerebrovascular disease. Emergency thrombectomy combined with medication therapy is currently the primary treatment for stroke. Inflammation and oxidative stress induced by ischemia-reperfusion cause secondary damage to blood vessels, especially endothelial mesenchymal transformation (EndoMT). However, much is still unclear about the role of EndoMT in ischemia-reperfusion. In this study, an in vivo ischemia-reperfusion model was established by transient middle cerebral artery occlusion (tMCAO) in wild-type (WT) C57BL/6 mice and NLRP3 (NOD-like receptor thermal protein domain associated protein 3) knockout (KO) C57BL/6 mice. An in vitro ischemia-reperfusion model was established by oxygen glucose deprivation and reoxygenation (OGD/R) of human brain microvascular endothelial cells (HBMECs). α-SMA (alpha smooth muscle actin), CD31 (platelet endothelial cell adhesion molecule-1, PECAM-1/CD31), NDUFC2 (NADH: ubiquinone oxidoreductase subunit C2), and NLRP3 were used to evaluate EndoMT and inflammation. Real-time PCR measured superoxide dismutase 1 (SOD1) and catalase (CAT) mRNA expression to evaluate oxidative stress levels. NLRP3 was activated by ischemia-reperfusion injury and NLRP3 inactivation inhibited the EndoMT in tMCAO mice. Further experiments demonstrated that OGD/R treatment induced NLRP3 activation and EndoMT in HBMECs, which resulted in NDUFC2 deficiency. NDUFC2 overexpression suppressed NLRP3 activation and EndoMT in HBMECs induced by OGD/R. Moreover, NDUFC2 overexpression rescued SOD1 and CAT mRNA expression. These results demonstrated that NDUFC2 deficiency decreased the antioxidant levels, leading to NLRP3 activation and EndoMT during ischemia-reperfusion injury and suggesting that NDUFC2 is a potential drug target for the treatment of ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

NDUFC2 deficiency exacerbates endothelial mesenchymal transformation during ischemia-reperfusion via NLRP3

Chen¹,

Liu²,

Bi³

et al. 2023

NeuroReport

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“…CircHECTD1 was upregulated in the MCAO model of mice and in the OGD/R model of HBMECs. As a miR-335 sponge, it negatively regulated the expression of miR-335 [ 61 ]. Recent reports revealed that miR-335 can repress EndoMT and promote cell migration and tube formation via regulation of NOTCH2.…”

Section: Circrnas and Strokementioning

confidence: 99%

“…Recent reports revealed that miR-335 can repress EndoMT and promote cell migration and tube formation via regulation of NOTCH2. Knockdown of circHECTD1 in both mouse MCAO model and HBMECs OGD model decreased NOTCH2 expression and promoted HBMECs migration and tube formation, while suppressing the EndoMT process [ 61 ].…”

Section: Circrnas and Strokementioning

confidence: 99%

Circular RNAs: Promising Treatment Targets and Biomarkers of Ischemic Stroke

Xu,

Liu,

Wang

et al. 2023

IJMS

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Ischemic stroke is one of the most significant causes of morbidity and mortality worldwide. However, there is a dearth of effective drugs and treatment methods for ischemic stroke. Significant numbers of circular RNAs (circRNAs) exhibit abnormal expression following ischemic stroke and are considered potential therapeutic targets. CircRNAs have emerged as promising biomarkers due to their stable expression in peripheral blood and their potential significance in ischemic stroke diagnosis and prognosis. This review provides a summary of 31 circRNAs involved in the pathophysiological processes of apoptosis, autophagy, inflammation, oxidative stress, and angiogenesis following ischemic stroke. Furthermore, we discuss the mechanisms of action of said circRNAs and their potential clinical applications. Ultimately, circRNAs exhibit promise as both therapeutic targets and biomarkers for ischemic stroke.

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“…Vascular brain damages due to EndMT were reversed by overexpression of the miRNA Let-7i ( 116 ). Additional miRNAs were found to regulate EndMT in the context of ischemic brain injuries, including the CircHECTD1 miRNA discussed above ( 117 ). In addition, it has been suggested that the endothelial dysfunction induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might initiate pulmonary fibrosis and vascular remodeling through EndMT ( 118 , 119 ).…”

Section: Other Factors Influencing Endmtmentioning

confidence: 99%

Endothelial Cell Phenotype, a Major Determinant of Venous Thrombo-Inflammation

Pilard

Gourdou-Latyszenok

Couturaud

et al. 2022

Front. Cardiovasc. Med.

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Reduced blood flow velocity in the vein triggers inflammation and is associated with the release into the extracellular space of alarmins or damage-associated molecular patterns (DAMPs). These molecules include extracellular nucleic acids, extracellular purinergic nucleotides (ATP, ADP), cytokines and extracellular HMGB1. They are recognized as a danger signal by immune cells, platelets and endothelial cells. Hence, endothelial cells are capable of sensing environmental cues through a wide variety of receptors expressed at the plasma membrane. The endothelium is then responding by expressing pro-coagulant proteins, including tissue factor, and inflammatory molecules such as cytokines and chemokines involved in the recruitment and activation of platelets and leukocytes. This ultimately leads to thrombosis, which is an active pro-inflammatory process, tightly regulated, that needs to be properly resolved to avoid further vascular damages. These mechanisms are often dysregulated, which promote fibrinolysis defects, activation of the immune system and irreversible vascular damages further contributing to thrombotic and inflammatory processes. The concept of thrombo-inflammation is now widely used to describe the complex interactions between the coagulation and inflammation in various cardiovascular diseases. In endothelial cells, activating signals converge to multiple intracellular pathways leading to phenotypical changes turning them into inflammatory-like cells. Accumulating evidence suggest that endothelial to mesenchymal transition (EndMT) may be a major mechanism of endothelial dysfunction induced during inflammation and thrombosis. EndMT is a biological process where endothelial cells lose their endothelial characteristics and acquire mesenchymal markers and functions. Endothelial dysfunction might play a central role in orchestrating and amplifying thrombo-inflammation thought induction of EndMT processes. Mechanisms regulating endothelial dysfunction have been only partially uncovered in the context of thrombotic diseases. In the present review, we focus on the importance of the endothelial phenotype and discuss how endothelial plasticity may regulate the interplay between thrombosis and inflammation. We discuss how the endothelial cells are sensing and responding to environmental cues and contribute to thrombo-inflammation with a particular focus on venous thromboembolism (VTE). A better understanding of the precise mechanisms involved and the specific role of endothelial cells is needed to characterize VTE incidence and address the risk of recurrent VTE and its sequelae.

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Knockdown of circHECTD1 inhibits oxygen-glucose deprivation and reperfusion induced endothelial-mesenchymal transition

Cited by 9 publications

References 48 publications

NDUFC2 deficiency exacerbates endothelial mesenchymal transformation during ischemia-reperfusion via NLRP3

NDUFC2 deficiency exacerbates endothelial mesenchymal transformation during ischemia-reperfusion via NLRP3

Circular RNAs: Promising Treatment Targets and Biomarkers of Ischemic Stroke

Endothelial Cell Phenotype, a Major Determinant of Venous Thrombo-Inflammation

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