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Vascular endothelial growth factor B (VEGF-B) has been shown to modulate metabolic processes and to induce physiological cardiac hypertrophy; thus, it could be cardioprotective in the failing myocardium. This study investigates the role of VEGF-B in cardiac proteomic and metabolic adaptation in HF during aldosterone and high-salt hypertensive challenges.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Male rats overexpressing the cardiac-specific VEGF-B transgene (VEGF-B TG) were treated for 3 or 6 weeks with deoxycorticosterone-acetate combined with a high-salt (HS) diet (DOCA + HS) to induce hypertension and cardiac damage. Extensive longitudinal echocardiographic studies of HF progression were conducted, starting at baseline. Sham-treated rats served as controls. To evaluate the metabolic alterations associated with HF, cardiac proteomics by mass spectrometry was performed. Hypertrophic non-treated VEGF-B TG hearts demonstrated high oxygen and adenosine triphosphate (ATP) demand with early onset of diastolic dysfunction. Administration of DOCA + HS to VEGF-B TG rats for 6 weeks amplified the progression from cardiac hypertrophy to HF, with a drastic drop in heart ATP concentration. Dobutamine stress echocardiographic analyses uncovered a significantly impaired systolic reserve. Mechanistically, the hallmark of the failing TG heart was an abnormal energy metabolism with decreased mitochondrial ATP, preceding the attenuated cardiac performance and leading to systolic HF.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study shows that the VEGF-B TG accelerates metabolic maladaptation which precedes structural cardiomyopathy in experimental hypertension and ultimately leads to systolic HF.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvad040","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T15:23:41Z","timestamp":1679585021000},"page":"1553-1567","source":"Crossref","is-referenced-by-count":7,"title":["VEGF-B hypertrophy predisposes to transition from diastolic to systolic heart failure in hypertensive rats"],"prefix":"10.1093","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6317-2016","authenticated-orcid":false,"given":"Anne-Maj","family":"Samuelsson","sequence":"first","affiliation":[{"name":"Department of Biomedicine, University of Bergen , Jonas Leis vei 91, 5020 Bergen , Norway"},{"name":"Department of Medicine, Haukeland University Hospital , Jonas Leis vei 65, 5021 Bergen , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5156-7184","authenticated-orcid":false,"given":"Theda Ulrike Patricia","family":"Bartolomaeus","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center (ECRC), a joint cooperation between Charit\u00e9 Universit\u00e4tsmedizin Berlin and Max-Delbr\u00fcck-Center for Molecular Medicine , Lindenberger Weg 80, 13125 Berlin , Germany"},{"name":"Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association (MDC) , Robert-R\u00f6ssle-Stra\u00dfe 10, 13125 Berlin , Germany"},{"name":"Charit\u00e9 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt Universit\u00e4t zu Berlin, and Berlin Institute of Health , Charit\u00e9 platz 1, 10117 Berlin , Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin , Potsdamer Stra\u00dfe 58, 10785 Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harithaa","family":"Anandakumar","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center (ECRC), a joint cooperation between Charit\u00e9 Universit\u00e4tsmedizin Berlin and Max-Delbr\u00fcck-Center for Molecular Medicine , Lindenberger Weg 80, 13125 Berlin , Germany"},{"name":"Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association (MDC) , Robert-R\u00f6ssle-Stra\u00dfe 10, 13125 Berlin , Germany"},{"name":"Charit\u00e9 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie 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