{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:32:37Z","timestamp":1793151157057,"version":"4.5.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>Excess sodium intake induces vascular dysfunction. Molecular mechanisms underlying this are unclear. Here we investigated the role of reactive oxygen species (ROS), Ca2+ signaling and inflammation in salt-induced vascular injury, focusing on the interplay between redox-sensitive Poly(ADP-ribose) polymerase (PARP), which activates transient receptor potential melastatin 2 (TRPM2) Ca2+ channel, and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome. Specifically, we sought to determine if salt excess induces a pro-oxidant environment, leading to PARP-induced TRPM2 activation and increased Ca2+ influx, inflammasome assembly, and consequent vascular damage.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>Vascular smooth muscle cells (VSMCs) from rats and humans were exposed to normal NaCl (140 mM) and high-salt conditions (180 mM).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>High salt increased ROS generation, PARP activation, and TRPM2-mediated Ca2+ transients. Osmotic controls had no effect on these processes. High-salt medium promoted the release of pro-inflammatory cytokines interleukin-18 and interleukin-1\u03b2 and increased phosphorylation of myosin light chain (MLC) in VSMCs. These effects were attenuated by inhibitors of PARP (Olaparib), TRPM2 (8-Br-cADPR), and NLRP3 inflammasome (MCC950). To validate these findings in in vivo, mice were subjected to a high-salt diet (4% NaCl, 5 weeks), resulting in elevated blood pressure and vascular remodeling and dysfunction. Exposure of vessels to olaparib and MCC950 attenuated the hypercontractility associated with a high-salt diet.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Salt-induced vascular injury in hypertension involves ROS generation in VSMCs leading to activation of the PARP\/TRPM2 axis, increased Ca2+ influx, NLRP3 activation, and vascular injury. Our study provides new insights into molecular pathways involved in high-salt diet-induced vascular dysfunction, important in hypertension.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ajh\/hpaf071","type":"journal-article","created":{"date-parts":[[2025,4,27]],"date-time":"2025-04-27T07:58:18Z","timestamp":1745740698000},"page":"788-796","source":"Crossref","is-referenced-by-count":8,"title":["Salt-Induced Vascular Damage in Hypertension Involves Redox Activation of PARP\/TRPM2 Signaling and Inflammasome Assembly"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4885-6647","authenticated-orcid":false,"given":"Rheure","family":"Alves-Lopes","sequence":"first","affiliation":[{"name":"School of Medicine, Medical Sciences and Nutrition, University of Aberdeen , Aberdeen ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5158-9263","authenticated-orcid":false,"given":"Karla B","family":"Neves","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy & Biomedical Sciences, University of Strathclyde , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9392-3020","authenticated-orcid":false,"given":"Sheon","family":"Mary","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Health, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7328-4708","authenticated-orcid":false,"given":"Delyth","family":"Graham","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Health, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto C","family":"Montezano","sequence":"additional","affiliation":[{"name":"Research Institute of the McGill University Health 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