Surfactant-Derived Proteins as Markers of Alveolar Membrane Damage in Heart Failure

Background In heart failure (HF) alveolar-capillary membrane is abnormal. Surfactant-derived proteins (SPs) and plasma receptor for advanced-glycation-end-products (RAGE) have been proposed as lung damage markers. Methods Eighty-nine chronic HF and 17 healthy subjects were evaluated by echocardiography, blood parameters, carbon monoxide lung diffusion (DLCO) and cardiopulmonary exercise test. We measured immature SP-B, mature SP-B, SP-A, SP-D and RAGE plasma levels. Results Immature SP-B (arbitrary units), mature SP-A (ng/ml) and SP-D (ng/ml), but not mature SP-B (ng/ml) and RAGE (pg/ml) levels, were higher in HF than in controls [immature SP-B: 15.6 (13.1, 75th–25th interquartile range) Vs. 11.1 (6.4), p<0.01; SP-A, 29.6 (20.1) Vs. 18.3 (13.5), p = 0.01; SP-D: 125 (90) Vs. 78 (58), p<0.01]. Immature SP-B, SP-A, SP-D and RAGE values were related to DLCO, peak oxygen consumption, ventilatory efficiency, and brain natriuretic peptide (BNP), whereas plasma mature SP-B was not. The DLCO Vs. immature SP-B correlation was the strongest one. At multivariate analysis, RAGE was associated to age and creatinine, SP-A to DLCO and BNP, SP-D to BNP, mature SP-B to DLCO and creatinine, and immature SP-B only but strongly to DLCO. Conclusions Immature SP-B is the most reliable biological marker of alveolar-capillary membrane function in HF.

[1]  A. Iorio,et al.  Multiparametric comparison of CARvedilol, vs. NEbivolol, vs. BIsoprolol in moderate heart failure: the CARNEBI trial. , 2013, International journal of cardiology.

[2]  L. Pisani,et al.  Opposite behavior of plasma levels surfactant protein type B and receptor for advanced glycation end products in pulmonary sarcoidosis. , 2013, Respiratory medicine.

[3]  G. Parati,et al.  Acute high-altitude exposure reduces lung diffusion: Data from the HIGHCARE Alps project , 2013, Respiratory Physiology & Neurobiology.

[4]  G. Ma,et al.  Serum surfactant protein D is associated with the prognosis in patients with chronic kidney disease , 2013, Journal of cardiovascular medicine.

[5]  R. Pellegrino,et al.  Role of Alveolar β2-Adrenergic Receptors on Lung Fluid Clearance and Exercise Ventilation in Healthy Humans , 2013, PloS one.

[6]  E. Tremoli,et al.  Kinetics of plasma SPB and RAGE during mechanical ventilation in patients undergoing major vascular surgery , 2011, Respiratory Physiology & Neurobiology.

[7]  N. Anthonisen,et al.  Circulating surfactant protein-D and the risk of cardiovascular morbidity and mortality. , 2011, European heart journal.

[8]  M. Elmlinger,et al.  Comprehensive characterisation of pulmonary and serum surfactant protein D in COPD , 2011, Respiratory research.

[9]  M. Brioschi,et al.  Surfactant protein B and RAGE increases in the plasma during cardiopulmonary bypass: a pilot study , 2010, European Respiratory Journal.

[10]  P. Agostoni,et al.  Effects of beta-blockers on ventilation efficiency in heart failure. , 2010, American heart journal.

[11]  E. Tremoli,et al.  Circulating Plasma Surfactant Protein Type B as Biological Marker of Alveolar-Capillary Barrier Damage in Chronic Heart Failure , 2009, Circulation. Heart failure.

[12]  T. Mukherjee,et al.  Implication of receptor for advanced glycation end product (RAGE) in pulmonary health and pathophysiology , 2008, Respiratory Physiology & Neurobiology.

[13]  P. Parsons,et al.  Plasma receptor for advanced glycation end products and clinical outcomes in acute lung injury , 2008, Thorax.

[14]  K. Motoyoshi,et al.  Serum surfactant protein-A, but not surfactant protein-D or KL-6, can predict preclinical lung damage induced by smoking , 2008, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[15]  P. Shekelle,et al.  Diagnosis and Management of Stable Chronic Obstructive Pulmonary Disease: A Clinical Practice Guideline from the American College of Physicians , 2007, Annals of Internal Medicine.

[16]  P. Agostoni,et al.  Lung function with carvedilol and bisoprolol in chronic heart failure: Is β selectivity relevant? , 2007, European journal of heart failure.

[17]  U. Holmskov,et al.  Surfactant protein A and surfactant protein D variation in pulmonary disease. , 2007, Immunobiology.

[18]  Manuela Muratori,et al.  Gas diffusion and alveolar-capillary unit in chronic heart failure. , 2006, European heart journal.

[19]  J. Pérez-Gil,et al.  Protein-lipid interactions and surface activity in the pulmonary surfactant system. , 2006, Chemistry and physics of lipids.

[20]  M. Kamran,et al.  Surfactant proteins SP-A and SP-D: structure, function and receptors. , 2006, Molecular immunology.

[21]  A. Bersten,et al.  CIRCULATING SURFACTANT PROTEIN‐B LEVELS INCREASE ACUTELY IN RESPONSE TO EXERCISE‐INDUCED LEFT VENTRICULAR DYSFUNCTION , 2005, Clinical and experimental pharmacology & physiology.

[22]  K. Wasserman,et al.  Work‐rate affects cardiopulmonary exercise test results in heart failure , 2005, European journal of heart failure.

[23]  P. Aylward,et al.  Plasma Surfactant Protein-B: A Novel Biomarker in Chronic Heart Failure , 2004, Circulation.

[24]  A. Bersten,et al.  Prolonged alveolocapillary barrier damage after acute cardiogenic pulmonary edema* , 2003, Critical care medicine.

[25]  J. Whitsett,et al.  Hydrophobic surfactant proteins in lung function and disease. , 2002, The New England journal of medicine.

[26]  E. Swenson,et al.  Pathogenesis of high-altitude pulmonary edema: inflammation is not an etiologic factor. , 2002, JAMA.

[27]  G. Pontone,et al.  Alveolar--capillary membrane gas conductance: a novel prognostic indicator in chronic heart failure. , 2002, European heart journal.

[28]  A. Schmidt,et al.  The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses. , 2001, The Journal of clinical investigation.

[29]  M. Guazzi,et al.  Lack of improvement of lung diffusing capacity following fluid withdrawal by ultrafiltration in chronic heart failure. , 2000, Journal of the American College of Cardiology.

[30]  J. Goerke,et al.  Pulmonary surfactant: functions and molecular composition. , 1998, Biochimica et biophysica acta.

[31]  A. Taylor,et al.  Evolution of resting lung function in the first year after cardiac transplantation. , 1995, The European respiratory journal.

[32]  Y. C. Huang,et al.  Normal values for single exhalation diffusing capacity and pulmonary capillary blood flow in sitting, supine positions, and during mild exercise. , 1994, Chest.

[33]  J E Cotes,et al.  Lung volumes and forced ventilatory flows , 1993, European Respiratory Journal.

[34]  J E Cotes,et al.  Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. , 1993, The European respiratory journal. Supplement.

[35]  P. Wollmer,et al.  Integrity of the alveolar-capillary barrier and alveolar surfactant system in smokers. , 1992, Thorax.

[36]  H. Schägger,et al.  Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. , 1987, Analytical biochemistry.

[37]  B. Whipp,et al.  A new method for detecting anaerobic threshold by gas exchange. , 1986, Journal of applied physiology.

[38]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[39]  J. Cotes,et al.  Iron-deficiency anaemia: its effect on transfer factor for the lung (diffusiong capacity) and ventilation and cardiac frequency during sub-maximal exercise. , 1972, Clinical science.

[40]  K. Motoyoshi,et al.  Serum surfactant protein-A, but not surfactant protein-D or KL-6, can predict preclinical lung damage induced by smoking. , 2008, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[41]  David Hinkley,et al.  Bootstrap Methods: Another Look at the Jackknife , 2008 .

[42]  J. Wright.  Immunoregulatory functions of surfactant proteins , 2005, Nature Reviews Immunology.

[43]  C. Stanford,et al.  Reproducibility of cardiopulmonary parameters during exercise in patients with chronic cardiac failure. The need for a preliminary test. , 1990, European heart journal.