Abstract 1278: Protective Myocardial Effects of the Healing Promoting Factor Secretory Leucocyte Protease Inhibitor in the Heart
Background: SLPI (secretory leucocyte protease inhibitor) is a potent inhibitor of serine proteases with important functions in immunity and healing processes. SLPI knockout mice display impaired wound healing with increased inflammation, transforming growth factor β, and matrix metalloproteinase activity. In fact, SLPI is one of the first identified factors promoting healing so far. Since healing defects can contribute to left ventricular remodeling after myocardial infarction and to the development of heart failure, we determined the expression and function of SLPI in the heart.
Methods and results. In vitro SLPI expression was readily detected in neonatal rat ventricular myocytes by western and northern blots as well as immunohistochemistry. Survival after hydrogen peroxide challenge was significantly enhanced after pretreatment with SLPI. In parallel, SLPI significantly reduced oxidative stress, and increased glutathione content. In vivo, mice with targeted deletion of SLPI had decreased survival after coronary artery ligation when compared to wildtype animals. Levels of matrixmetalloproteinase 9 were increased after myocardial infarction indicating profound changes of extracellular matrix remodeling in KO mice. In line with the in vitro results, oxidative stress was increased in KO mice. To underline the importance of SLPI in patients with heart failure, SLPI serum levels were measured by ELISA and were significantly higher in patients with heart failure when compared to matched healthy volunteers (59.25±2.39 vs. 45.27±3.63 ng/ml, p=0.01).
Conclusion: SLPI is expressed in cardiac myocytes and protects against oxidative stress in vitro and in vivo. Elevated serum SLPI levels in human chronic heart failure, decreased survival and changes in extracellular matrix remodeling of SLPI knockout mice after myocardial infarction suggest an important pathophysiologic function of SLPI in heart failure.