Immature surfactant protein-B impairs the antioxidant capacity of HDL

Published:February 27, 2019DOI:https://doi.org/10.1016/j.ijcard.2019.02.057

      Highlights

      • proSP-B is a potential diagnostic and prognostic circulating HF marker.
      • It binds to human HDL particles impairing their antioxidant capacity.
      • proSP-B might contribute to the reduction of defense against oxidative stress in HF.

      Abstract

      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.

      Graphical abstract

      Abbreviations:

      ACE (angiotensin-converting enzyme), ACM (alveolar-capillary membrane), apoA-I (apolipoprotein A-I), apoA-II (apolipoprotein A-II), apoM (apolipoprotein M), AT1 (angiotensin II subtype 1 receptor), BMI (body mass index), BNP (B-type natriuretic peptide), CHO (Chinese hamster ovary), COPD (chronic obstructive pulmonary disease), DCF (Dichlorofluorescein), DLCO (carbon monoxide lung diffusion), ESRD (end-stage renal disease), Hb (haemoglobin), HDL (high-density lipoprotein), HF (heart failure), HOI (HDL oxidant index), LCAT (lecithin: cholesterol acyl transferase), LC-MS (liquid chromatography-mass spectrometry), LDL (low-density lipoprotein), LVEF (left ventricular ejection fraction), NT-proBNP (N-terminal pro–B-type natriuretic peptide), NYHA (New York Heart Association), PLA2 (phospholipase A2), PON-1 (paraoxonase-1), proSP-B (immature surfactant protein B), SD (standard deviation), SDS-PAGE (sodium dodecyl sulphate-polyacrylamide gel electrophoresis), SP-A (surfactant protein A), SP-B (surfactant protein B), SP-C (surfactant protein C), SP-D (surfactant protein D), VCO2 (carbon dioxide production), VE (minute ventilation), VLDL (very low-density lipoprotein), VO2 (oxygen consumption)

      Keywords

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