Exogenous galectin-1 mitigates inflammation and lipopolysaccharide-induced myocardial injury in experimental sepsis

Myocardial injury is common in sepsis and may be attributed to overwhelming inflammation and mitochondrial dysfunction. Galectin-1 (Gal1) is an immunomodulatory protein, but its role in sepsis-associated cardiac dysfunction remains unclear. We enrolled 125 septic ICU patients, including 34 (27.2%) with initially low cardiac output (CO < 4.0 L/min). Patients with low CO had impaired cardiac contractility, greater disease severity, higher mortality, and higher circulating Gal1 and NT-proBNP concentrations. Experimental sepsis was induced by lipopolysaccharide in male mice. Septic mice developed transient reductions in CO and left ventricular ejection fraction during the first 24 h after LPS injection. Treatment with recombinant Gal1 (rGal1) was associated with attenuated cardiac dysfunction and improved survival in the murine model. In vitro, pre-treatment with rGal1 showed a trend toward reduced inflammatory cytokine production in cultured macrophages and attenuated mitochondrial membrane depolarization in cultured cardiomyocytes. Overall, circulating Gal1 was associated with greater disease severity and mortality in septic patients; whereas rGal1 treatment was associated with improved cardiac function and survival in experimental sepsis. These findings support further investigation of the biological role of Gal1 in sepsis but require validation in additional experimental models and independent clinical studies before any prognostic or therapeutic application can be established.