A venous-specific purinergic signaling cascade initiated by Pannexin 1 regulates TNFα-induced increases in endothelial permeability
Daniela Maier-Begandt,Daniela Maier-Begandt,Heather Skye Comstra,Samuel A. Molina,Nenja Krüger,Nenja Krüger,Claire A. Ruddiman,Yen Lin Chen,Xiaobin Chen,Lauren A Biwer,Scott R. Johnstone,Alexander W. Lohman,Miranda E. Good,Leon J. DeLalio,Kwangseok Hong,Hannah M. Bacon,Zhen Yan,Swapnil K. Sonkusare,Michael Koval,Brant E. Isakson +19 more
TLDR
In this article, the effects of the proinflammatory cytokine TNFα on transendothelial permeability and electrophysiology in ex vivo murine veins and arteries were studied.Abstract:
The endothelial cell barrier regulates the passage of fluid between the bloodstream and underlying tissues, and barrier function impairment exacerbates the severity of inflammatory insults. To understand how inflammation alters vessel permeability, we studied the effects of the proinflammatory cytokine TNFα on transendothelial permeability and electrophysiology in ex vivo murine veins and arteries. We found that TNFα specifically decreased the barrier function of venous endothelium without affecting that of arterial endothelium. On the basis of RNA expression profiling and protein analysis, we found that claudin-11 (CLDN11) was the predominant claudin in venous endothelial cells and that there was little, if any, CLDN11 in arterial endothelial cells. Consistent with a difference in claudin composition, TNFα increased the permselectivity of Cl- over Na+ in venous but not arterial endothelium. The vein-specific effects of TNFα also required the activation of Pannexin 1 (Panx1) channels and the CD39-mediated hydrolysis of ATP to adenosine, which subsequently stimulated A2A adenosine receptors. Moreover, the increase in vein permeability required the activation of the Ca2+ channel TRPV4 downstream of Panx1 activation. Panx1-deficient mice resisted the pathologic effects of sepsis induced by cecal ligation and puncture on life span and lung vascular permeability. These data provide a targetable pathway with the potential to promote vein barrier function and prevent the deleterious effects of vascular leak in response to inflammation.read more
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Empagliflozin attenuates cardiac microvascular ischemia/reperfusion through activating the AMPKα1/ULK1/FUNDC1/mitophagy pathway
C Cai,Zhongzhou Guo,Xing Chang,Ziying Li,Feng Wu,Jing He,Tiantian Cao,Kangrong Wang,Nengxian Shi,Hao Zhou,Sam Toan,David Muid,Yi-Peng Tan +12 more
TL;DR: In this paper , empagliflozin could reduce cardiac microvascular ischemia/reperfusion (I/R) injury by enhancing mitophagy in mice.
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Role of Transient Receptor Potential Vanilloid 4 in Vascular Function
Liangliang Liu,Mengting Guo,Xiaowang Lv,Zhiwei Wang,Jigang Yang,Yanting Li,Fan Yu,Xin Wen,Lei Feng,Tingting Zhou +9 more
TL;DR: Transient receptor potential vanilloid 4 (TRPV4) channels are widely expressed in systemic tissues and can be activated by many stimuli as mentioned in this paper, which can play an important role in the vasculature and is implicated in the regulation of cardiovascular homeostasis processes such as blood pressure, vascular remodeling, and pulmonary hypertension and edema.
Journal ArticleDOI
Pannexin 1 as a driver of inflammation and ischemia–reperfusion injury
Michael Koval,Aleksandra Cwiek,Thomas Carr,Miranda E. Good,Alexander W. Lohman,Alexander W. Lohman,Brant E. Isakson +6 more
TL;DR: Pannexin 1 (Panx1) is a ubiquitously expressed protein forming large conductance channels that are central to many distinct inflammation and injury responses as mentioned in this paper, and the ability of Panx1 to serve as a central component of many diverse physiologic responses has proven to be critically dependent on the context of expression, post-translational modification, interacting partners, and the mode of stimulation.
Journal ArticleDOI
Generation and Export of Red Blood Cell ATP in Health and Disease.
TL;DR: The ability of RBCs to adapt to the metabolic environment via differential control of these metabolites is impaired in the face of enzymopathies [pyruvate kinase deficiency; glucose-6-phosphate dehydrogenase (G6PD) deficiency], blood banking, diabetes mellitus, COVID-19 or sepsis, and sickle cell disease.
Journal ArticleDOI
Mitochondria regulate TRPV4-mediated release of ATP
TL;DR: Depolarised mitochondria switch TRPV4 signalling from relying on Ca-induced Ca release at IP receptors, to being independent of Ca influx and instead mediated by ATP release via pannexins, highlighting a previously unknown role of mitochondria in shaping TRpV4 mediated Ca signalling by facilitating ATP release.
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