Repetitive worsening of chronic heart failure promotes myocardial fibrosis through enhanced oxidant stress in vivo

Abstract Background: Progression of myocardial fibrosis (MF) is vital for prognosis of patients with chronic heart failure (CHF). Oxidant stress (OS) has been suggested to regulate collagen metabolism at the level of cellular experiments. In this study we clarified a possible link between enhancement of OS in vivo and progression of MF in patients with CHF. Methods: Nineteen patients with CHF were enrolled at admission because of its acute worsening. After conventional treatment (20 ± 12days later), serum level of brain-type natriuretic peptide was decreased from 965.5 ± 704.8 (acute phase) to 311.5 ± 271.4pg/ml (chronic phase). At these two phases, we monitored: 1) urinary excretion of immunoreactive 8-iso-prostaglandin F 2α (8-isoPGF 2α) , a marker for OS in vivo ; 2) serum total anti-oxidant status (TAS); and 3) serum levels of procollagen type I carboxyterminal peptide (PIP) and carboxyterminal collagen type I telopeptide (CITP), biochemical markers for collagen synthesis and degradation, respectively. Results: We found that 8-isoPGF 2α and PIP levels were enhanced at acute versus chronic phase (353.9 ± 329.8 vs. 221.2 ± 131.2pg/mg creatinine, P = 0.01; 150.7 ± 55.8 vs. 99.7 ± 39.1ng/ml, P = 0.001; respectively). TAS did not change throughout the observation (0.95 ± 0.15 vs. 0.96 ± 0.16mM). CITP was increased from acute to chronic phase (7.4 ± 4.1 to 13.0 ± 8.2ng/ml, P = 0.0001). Conclusions: OS and collagen synthesis were enhanced at the acute worsening of CHF, suggesting that repetitive worsening of CHF promotes MF through OS.