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Anti-Inflammatory Effects of Exercise Training in a Rat Model of Heart Failure with Preserved Ejection Fraction

2016; Lippincott Williams & Wilkins; Volume: 48; Linguagem: Inglês

10.1249/01.mss.0000485608.04402.f5

1530-0315

Cristine Schmidt, Nádia Gonçalves, Ana Filipa Silva, Dulce Fontoura, Sara Leite, Inês Falcão‐Pires, André P. Lourenço, José Oliveira, Adelino Leite‐Moreira, Daniel Moreira‐Gonçalves,

Cardiovascular and exercise physiology

PURPOSE:To examine, in an animal model of heart failure with preserved ejection fraction (HFpEF), whether exercise training (ExT) would be able to improve exercise capacity, diastolic function and exert an anti-inflammatory effect. METHODS: The study involved nine-week old control Wistar-Kyoto rats (WKY, n=8), ZSF1 lean rats (Lean, n=8) and ZSF1 obese (Ob n=16). At the 15th week, Ob rats were randomly divided in Ob sedentary (ObSED, n=8) and Ob exercised (ObEX, n=8; treadmill exercise training during 5 weeks, 5 days/week, 60 min/day, at a speed of 20m/min). In the 19th week, all animals undergo echocardiographic evaluation. At the end of the protocol (20th week), all animals performed a maximal oxygen consumption (VO2max) test, were sacrificed and blood samples were collected for plasma protein analysis by ELISA [interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-alpha), intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), malondialdehyde (MDA), protein carbonyl content (PCC), tissue inhibitors of metalloproteinases-1 (TIMP1), matrix metalloproteinases-9 (MMP9) and N-terminal pro-brain natriuretic peptide (NT-proBNP)]. RESULTS: ExT improved VO2max (18,29±2.01 vs 13,88±2,13) and attenuated diastolic dysfunction in ObEX (E/E´ ratio 14,33±2,27 vs 16,53±1,47, p<0,05). Exercised animals, compared to ObSED, showed reduced levels of IL-6, TNF-alpha, CRP, ICAM, BNP and MMP9 (p<0.05). No differences were found for VCAM, MDA, PCC and TIMP-1. The ratio E/E´ was negatively correlated with VO2max (r=-0,55; p=0,03) and positively correlated with IL-6 (r=0,7552; p=0,001), CRP (r=0,69; p=0.01) and MMP9 (r=0,79; p=0.00). In addition, VO2max was negatively correlated with IL-6 (r=-0,52; p=0.02), ICAM (r=-0,46; p=0.04) and MMP9 (r=-0,64; p=0.003). CONCLUSIONS: Regular exercise training improved exercise capacity and diastolic function. This was associated with reduced circulating levels of inflammatory cytokines and markers of endothelial dysfunction, neurohumoral activation and matrix metalloproteinases. FUNDING: Grant from the European Commission FP7-Health-2010; MEDIA-261,409. CIAFEL is funded by European Regional Development Fund through the Operational Competitiveness Programme, and by FCT of Portugal (UID/DTP/00617/2013).