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We have previously demonstrated that metabolic impairment delineated the heightened vulnerability of both the perivascular (PVAT) and perirenal adipose tissue (PRAT) depots to hypoxia and inflammation, predisposing to cardioautonomic, vascular and renal deterioration. Interventions either addressing underlying metabolic disturbances or halting adipose tissue dysfunction rescued the observed pathological and functional manifestations. Several lines of evidence implicate adipose tissue thromboinflammation, which entails the activation of the proinflammatory properties of the blood clotting cascade, in the pathogenesis of metabolic and cardiovascular diseases. Despite offering valuable tools to interrupt the thromboinflammatory cycle, there exists a significant knowledge gap regarding the potential pleiotropic effects of anticoagulant drugs on adipose inflammation and cardiovascular function. As such, a systemic investigation of the consequences of PVAT and PRAT thromboinflammation and its interruption in the context of metabolic disease has not been attempted. Here, using an established prediabetic rat model, we demonstrate that metabolic disturbances are associated with PVAT and PRAT thromboinflammation in addition to cardioautonomic, vascular and renal functional decline. Administration of rivaroxaban, a FXa inhibitor, reduced PVAT and PRAT thromboinflammation and ameliorated the cardioautonomic, vascular and renal deterioration associated with prediabetes. Our present work outlines the involvement of PVAT and PRAT thromboinflammation during early metabolic derangement and offers novel perspectives into targeting adipose tissue thrombo-inflammatory pathways for the management its complications in future translational efforts.<\/jats:p>","DOI":"10.1042\/cs20231186","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T18:32:25Z","timestamp":1708540345000},"page":"289-308","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Interruption of perivascular and perirenal adipose tissue thromboinflammation rescues prediabetic cardioautonomic and renovascular deterioration"],"prefix":"10.1042","volume":"138","author":[{"given":"Aya","family":"Al-Saidi","sequence":"first","affiliation":[{"name":"1Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim\u00a0F.","family":"Alzaim","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon"},{"name":"2Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safaa\u00a0H.","family":"Hammoud","sequence":"additional","affiliation":[{"name":"3Department of Pharmacology and Therapeutics, Beirut Arab University, Beirut, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghida","family":"Al Arab","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samaya","family":"Abdalla","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahed","family":"Mougharbil","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali\u00a0H.","family":"Eid","sequence":"additional","affiliation":[{"name":"4Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3432-3038","authenticated-orcid":false,"given":"Ahmed\u00a0F.","family":"El-Yazbi","sequence":"additional","affiliation":[{"name":"5Faculty of Pharmacy, Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt"},{"name":"6Faculty of Pharmacy and Research and Innovation Hub, Alamein International University, Alamein, Matrouh, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2024,3,5]]},"reference":[{"key":"2024030507350717200_B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11906-018-0812-z","article-title":"The global epidemic of the metabolic syndrome","volume":"20","author":"Saklayen","year":"2018","journal-title":"Curr. 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