RHOQ is induced by DLL4 and regulates angiogenesis by determining the intracellular route of the Notch intracellular domain

Bridges, Esther; Sheldon, Helen; Kleibeuker, Esther A.; Ramberger, Evelyn; Zois, Christos E.; Barnard, Alun R.; Harjes, Ulrike; Li, Jiliang; Masiero, Massimo; MacLaren, Robert E.; Harris, Adrian L.

doi:10.1007/s10456-020-09726-w

Cited by 22 publications

(16 citation statements)

References 52 publications

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“…Thrombosis initiation can occur courtesy of perturbations in the dynamic balance between pro- and anti-thrombotic activities in the endothelium, independent of denuded or physically disrupted endothelium 57 . Under pathological conditions, dysfunctional ECs upregulate pro-coagulant factors such as platelet adhesion molecules, tissue factors, plasminogen activator inhibitor-1 and downregulate anti-coagulant factors such as thrombomodulin, PGI2, and t-PA 58 , creating a pro-thrombotic microenvironment. For example, damaged ECs produce TXA2, which turns on platelet activation, adhesion and aggregation onto the vascular walls 59 .…”

Section: Coagulationmentioning

confidence: 99%

Coronary microvascular injury in myocardial infarction: perception and knowledge for mitochondrial quality control

et al. 2021

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Endothelial cells (ECs) constitute the innermost layer in all blood vessels to maintain the structural integrity and microcirculation function for coronary microvasculature. Impaired endothelial function is demonstrated in various cardiovascular diseases including myocardial infarction (MI), which is featured by reduced myocardial blood flow as a result of epicardial coronary obstruction, thrombogenesis, and inflammation. In this context, understanding the cellular and molecular mechanisms governing the function of coronary ECs is essential for the early diagnosis and optimal treatment of MI. Although ECs contain relatively fewer mitochondria compared with cardiomyocytes, they function as key sensors of environmental and cellular stress, in the regulation of EC viability, structural integrity and function. Mitochondrial quality control (MQC) machineries respond to a broad array of stress stimuli to regulate fission, fusion, mitophagy and biogenesis in mitochondria. Impaired MQC is a cardinal feature of EC injury and dysfunction. Hence, medications modulating MQC mechanisms are considered as promising novel therapeutic options in MI. Here in this review, we provide updated insights into the key role of MQC mechanisms in coronary ECs and microvascular dysfunction in MI. We also discussed the option of MQC as a novel therapeutic target to delay, reverse or repair coronary microvascular damage in MI. Contemporary available MQC-targeted therapies with potential clinical benefits to alleviate coronary microvascular injury during MI are also summarized.

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Section: Coagulationmentioning

confidence: 99%

Coronary microvascular injury in myocardial infarction: perception and knowledge for mitochondrial quality control

et al. 2021

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“…Total RNA was isolated from RAW264.7 macrophages using RNAiso Plus (TaKaRa) [ 33 , 34 ]. RNA was converted into cDNA using PrimeScript RT Mix (TaKaRa).…”

Section: Methodsmentioning

confidence: 99%

BTK Promotes Atherosclerosis by Regulating Oxidative Stress, Mitochondrial Injury, and ER Stress of Macrophages

Qiu

Chen

et al. 2021

Oxidative Medicine and Cellular Longevity

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Atherosclerosis (AS) is a chronic metabolic disease in arterial walls, characterized by lipid deposition and persistent aseptic inflammation. AS is regarded as the basis of a variety of cardiovascular and cerebrovascular diseases. It is widely acknowledged that macrophages would become foam cells after internalizing lipoprotein particles, which is an initial factor in atherogenesis. Here, we showed the influences of Bruton’s tyrosine kinase (BTK) in macrophage-mediated AS and how BTK regulates the inflammatory responses of macrophages in AS. Our bioinformatic results suggested that BTK was a potential hub gene, which is closely related to oxidative stress, ER stress, and inflammation in macrophage-induced AS. Moreover, we found that BTK knockdown could restrain ox-LDL-induced NK-κB signaling activation in macrophages and repressed M1 polarization. The mechanistic studies revealed that oxidative stress, mitochondrial injury, and ER stress in macrophages were also suppressed by BTK knockdown. Furthermore, we found that sh-BTK adenovirus injection could alleviate the severity of AS in ApoE-/- mice induced by a high-fat diet in vivo. Our study suggested that BTK promoted ox-LDL-induced ER stress, oxidative stress, and inflammatory responses in macrophages, and it may be a potential therapeutic target in AS.

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“…After TUNEL labeling and DAPI counterstain, images were captured by fluorescence microscopy. Apoptosis was expressed as a percentage relative to the control group [ 44 , 45 ].…”

Section: Methodsmentioning

confidence: 99%

Protective Effect of Optic Atrophy 1 on Cardiomyocyte Oxidative Stress: Roles of Mitophagy, Mitochondrial Fission, and MAPK/ERK Signaling

Wang

Han

et al. 2021

Oxidative Medicine and Cellular Longevity

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Myocardial infarction is associated with oxidative stress and mitochondrial damage. However, the regulatory mechanisms underlying cardiomyocyte oxidative stress during myocardial infarction are not fully understood. In the present study, we explored the cardioprotective action of optic atrophy 1- (Opa1-) mediated mitochondrial autophagy (mitophagy) in oxidative stress-challenged cardiomyocytes, with a focus on mitochondrial homeostasis and the MAPK/ERK pathway. Our results demonstrated that overexpression of Opa1 in cultured rat H9C2 cardiomyocytes, a procedure that stimulates mitophagy, attenuates oxidative stress and increases cellular antioxidant capacity. Activation of Opa1-mediated mitophagy suppressed cardiomyocyte apoptosis by downregulating Bax, caspase-9, and caspase-12 and upregulating Bcl-2 and c-IAP. Using mitochondrial tracker staining and a reactive oxygen species indicator, our assays showed that Opa1-mediated mitophagy attenuated mitochondrial fission and reduced ROS production in cardiomyocytes. In addition, we found that inhibition of the MAPK/ERK pathway abolished the antioxidant action of Opa1-mediated mitophagy in these cells. Taken together, our data demonstrate that Opa1-mediated mitophagy protects cardiomyocytes against oxidative stress damage through inhibition of mitochondrial fission and activation of MAPK/ERK signaling. These findings reveal a critical role for Opa1 in the modulation of cardiomyocyte redox balance and suggest a potential target for the treatment of myocardial infarction.

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RHOQ is induced by DLL4 and regulates angiogenesis by determining the intracellular route of the Notch intracellular domain

Cited by 22 publications

References 52 publications

Coronary microvascular injury in myocardial infarction: perception and knowledge for mitochondrial quality control

Coronary microvascular injury in myocardial infarction: perception and knowledge for mitochondrial quality control

BTK Promotes Atherosclerosis by Regulating Oxidative Stress, Mitochondrial Injury, and ER Stress of Macrophages

Protective Effect of Optic Atrophy 1 on Cardiomyocyte Oxidative Stress: Roles of Mitophagy, Mitochondrial Fission, and MAPK/ERK Signaling

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