Immature surfactant protein-B impairs the antioxidant capacity of HDL

Circulating immature surfactant protein B (proSP-B) forms emerged as the most reliable lung-specific circulating marker for alveolar-capillary membrane (ACM) dysfunction and for the overall clinical status of heart failure (HF). Notably, in terms of HF hospitalization, immature SP-B overwhelms the prognostic role of other most frequently used clinical parameters such as those related to lung dysfunction. The strong prognostic value of circulating proSP-B in HF suggests more widespread and possible systemic effects. Thus, we assessed the plasma distribution of proSP-B evaluating whether it exists in a lipoprotein-bound form and its impact on lipoprotein structure and function. ProSP-B forms were detectable in high-density lipoprotein (HDL) only. To assess the impact of proSP-B on HDL, HDL from healthy subjects were enriched with proSP-B produced by a stably transfected CHO cell line that specifically expresses and releases the human proSP-B. After enrichment, HDL size and lipoprotein electrophoretic mobility, and protein composition did not show apparent differences. HDL antioxidant capacity (HOI), assessed as their ability to inhibit air-induced LDL oxidation, was impaired after proSP-B enrichment. HOI was also higher in HF patients with respect to age-matched control healthy subjects (p = 0.013). Circulating proSP-B, besides its potential role as a specific marker for ACM dysfunction in HF patients with diagnostic and prognostic value, binds to human HDL impairing their antioxidant capacity. These findings shed light on proSP-B as a molecule that contributes to the reduction of the defense against oxidative stress, a key mediator in the pathogenesis of HF. (C) 2019 Elsevier B.V. All rights reserved.