Helmholtz Gemeinschaft


VEGF-B hypertrophy predisposes to transition from diastolic to systolic heart failure in hypertensive rats

PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
[img] Other (Supplementary Data)

Item Type:Article
Title:VEGF-B hypertrophy predisposes to transition from diastolic to systolic heart failure in hypertensive rats
Creators Name:Samuelsson, A.M. and Bartolomaeus, T.U.P. and Anandakumar, H. and Thowsen, I. and Nikpey, E. and Han, J. and Marko, L. and Finne, K. and Tenstad, O. and Eckstein, J. and Berndt, N. and Kühne, T. and Kedziora, S. and Sultan, I. and Skogstrand, T. and Karlsen, T.V. and Nurmi, H. and Forslund, S.K. and Bollano, E. and Alitalo, K. and Muller, D.N. and Wiig, H.
Abstract:AIMS: Cardiac energy metabolism is centrally involved in heart failure (HF), although the direction of the metabolic alterations is complex and likely dependent on the particular stage of HF progression. 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. METHODS AND RESULTS: 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. CONCLUSIONS: This study shows that the VEGF-B TG accelerates metabolic maladaptation which precedes structural cardiomyopathy in experimental hypertension and ultimately leads to systolic HF.
Keywords:VEGF-B, Heart Failure, Cardiac Hypertrophy, Metabolism, Salt, Aldosterone, Animals, Rats
Source:Cardiovascular Research
Publisher:Oxford University Press
Page Range:1553-1567
Date:4 July 2023
Additional Information:Erratum in: Cardiovasc Res 2023: cvad040.
Official Publication:https://doi.org/10.1093/cvr/cvad040
PubMed:View item in PubMed

Repository Staff Only: item control page


Downloads per month over past year

Open Access
MDC Library