Oncostatin M mediates cardioprotection via angiogenesis in ischemic heart disease.

Objective: Oncostatin M (OSM) is an inflammatory cytokine belonging to the interleukin-6 family member, which plays an important role in various cardiovascular diseases. We recently reported increased serum OSM levels in patients with coronary artery disease. However, the specific role in HF with ischemic heart disease (IHD) remains unclear. Methods and results: A total of 120 patients with HF and 48 control subjects were enrolled in this study. Serum OSM levels were measured using a sandwich technique immunoassay during the compensated state. The results revealed significantly higher serum OSM levels in HF patients compared to controls. Importantly, HF patients with IHD had higher OSM levels, and those with collateral flow showed the even higher levels, indicating a potential involvement in angiogenesis. Furthermore, a positive correlation was found between serum OSM levels and levels of vascular endothelial growth factor (VEGF). In vitro experiments demonstrated that recombinant OSM upregulated VEGF production in cultured human coronary artery endothelial cells. We additionally observed that endogenous OSM levels were enhanced through exercise. Lastly, we identified the potential of SGLT2 inhibitors to enhance OSM production. Conclusions: Serum OSM levels were elevated in HF patients, particularly in those with IHD Our data indicated that endogenous OSM induces VEGF production in the heart, suggesting the activation of angiogenesis, which can be further enhanced by exercise or SGLT2 inhibitors.