Septic cardiomyopathy affects up to 70% of patients with septic shock and the derangement of cardiac mitochondrial function contributes to the likelihood of death. However, at present, there is no specific therapeutic drug available. The peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α) and coactivator-1β (PGC-1β) modulate members of the PPARs, which regulate mitochondrial energy metabolism and the production of mitochondrial reactive oxygen species in the heart. This study investigated the potential of the newly developed synthetic antimicrobial peptide 19-2.5 (Pep2.5) to attenuate mitochondrial dysfunction in murine cardiomyocytes stimulated with serum from septic shock patients. Pep2.5 treatment attenuated the suppression of PPAR-α, PPAR-γ ( P = 0.0004 and P = 0.0001, respectively) and PGC-1α/β ( P = 0.0008 and P = 0.0147, respectively) in cardiomyocytes stimulated with serum from septic shock patients compared with untreated cells. Pep2.5 treatment enhanced the mitochondrial maximum respiration ( P < 0.0001), increased cellular ATP levels ( P < 0.0001) and reduced the production of mitochondrial reactive oxygen species. Thus, the administration of Pep2.5 may have the potential as a promising therapeutic approach in septic cardiomyopathy by attenuating mitochondrial dysfunction in the septic heart.
Keywords: HL-1 cells; Septic cardiomyopathy; antimicrobial peptide; mitochondrial reactive oxygen species.