{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:29:10Z","timestamp":1792042150979,"version":"4.4.0"},"reference-count":271,"publisher":"Portland Press Ltd.","issue":"20","license":[{"start":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T00:00:00Z","timestamp":1698192000000},"content-version":"vor","delay-in-days":24,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,10,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In the vascular wall, the Na,K-ATPase plays an important role in the control of arterial tone. Through cSrc signaling, it contributes to the modulation of Ca2+ sensitivity in vascular smooth muscle cells. This review focuses on the potential implication of Na,K-ATPase-dependent intracellular signaling pathways in severe vascular disorders; ischemic stroke, familial migraine, and arterial hypertension. We propose similarity in the detrimental Na,K-ATPase-dependent signaling seen in these pathological conditions. The review includes a retrospective proteomics analysis investigating temporal changes after ischemic stroke. The analysis revealed that the expression of Na,K-ATPase \u03b1 isoforms is down-regulated in the days and weeks following reperfusion, while downstream Na,K-ATPase-dependent cSrc kinase is up-regulated. These results are important since previous studies have linked the Na,K-ATPase-dependent cSrc signaling to futile recanalization and vasospasm after stroke. The review also explores a link between the Na,K-ATPase and migraine with aura, as reduced expression or pharmacological inhibition of the Na,K-ATPase leads to cSrc kinase signaling up-regulation and cerebral hypoperfusion. The review discusses the role of an endogenous cardiotonic steroid-like compound, ouabain, which binds to the Na,K-ATPase and initiates the intracellular cSrc signaling, in the pathophysiology of arterial hypertension. Currently, our understanding of the precise control mechanisms governing the Na,K-ATPase\/cSrc kinase regulation in the vascular wall is limited. Understanding the role of vascular Na,K-ATPase signaling is essential for developing targeted treatments for cerebrovascular disorders and hypertension, as the Na,K-ATPase is implicated in the pathogenesis of these conditions and may contribute to their comorbidity.<\/jats:p>","DOI":"10.1042\/cs20220796","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T07:25:12Z","timestamp":1698218712000},"page":"1595-1618","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The vascular Na,K-ATPase: clinical implications in stroke, migraine, and hypertension"],"prefix":"10.1042","volume":"137","author":[{"given":"Christian","family":"Staehr","sequence":"first","affiliation":[{"name":"1Department of Biomedicine, Aarhus University, H\u00f8egh-Guldbergsgade 10, 8000 Aarhus, Denmark"},{"name":"2Department of Renal Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 35, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5431-4409","authenticated-orcid":false,"given":"Christian","family":"Aalkjaer","sequence":"additional","affiliation":[{"name":"1Department of Biomedicine, Aarhus University, H\u00f8egh-Guldbergsgade 10, 8000 Aarhus, Denmark"},{"name":"3Danish Cardiovascular Academy, H\u00f8egh-Guldbergsgade 10, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir\u00a0V.","family":"Matchkov","sequence":"additional","affiliation":[{"name":"1Department of Biomedicine, Aarhus University, H\u00f8egh-Guldbergsgade 10, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2023,10,25]]},"reference":[{"key":"2023102507250189200_B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fphys.2017.00371","article-title":"The structure and function of the Na,K-ATPase isoforms in health and disease","volume":"8","author":"Clausen","year":"2017","journal-title":"Front. 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