title: Inflammatory markers and circulating extracellular matrix proteins in patients with chronic obstructive pulmonary disease and left ventricular diastolic dysfunction.
abstract: BACKGROUND
  Left ventricular diastolic dysfunction (LVDD) is a frequent condition in chronic obstructive pulmonary disease (COPD). Tenascin-C (Tn-C) and matrix metalloproteinase-9 (MMP-9) are extracellular matrix proteins associated with myocardial fibrosis and wall remodeling because of inflammation.
  
  
  OBJECTIVE
  To determine whether the circulating levels of inflammatory markers, Tn-C and MMP-9 are associated with LVDD in COPD patients.
  
  
  METHODS
  Forty-two severe stable COPD patients (64 ± 8 years, 88% male, FEV1% 38 ± 5.7) and a control group (n = 11) were included. Pulmonary function tests and a Doppler echocardiography were performed on COPD patients. Baseline serum levels of C-reactive protein (CRP), leukocytes, fibrinogen, interleukins (IL) 6 and 8, Tn-C and MMP-9 were analyzed in all participants.
  
  
  RESULTS
  COPD patients were classified in two groups: LVDD (n = 35) and non-LVDD (n = 7). Serum levels of IL-6 and CRP were higher in the LVDD group compared to the non-LVDD group [median(IQR)] [3.46 pg/mL (2.36-4.74) vs 1.87 pg/mL (1.10-3.28), P = 0.045] and [6.0 mg/L (3.0-13.0) vs 1.0 mg/L (1.0-2.3), P = 0.001], respectively. The same trend was observed in the analysis adjusted by age and BMI, being significant for CRP (P = 0.04). Circulating IL-6 was associated with the type of LVDD, being higher in the type-II (P = 0.046). Obese patients with COPD-LVDD showed a higher level of inflammatory markers (P = 0.021). Tn-C were significantly higher in patients with LVDD type-II compared to type-I [1422 ng/mL (826-1948) vs 781 ng/mL (640-1139), P = 0.015], without differences in MMP-9.
  
  
  CONCLUSIONS
  Severe COPD patients with LVDD showed a different inflammatory pattern, suggesting a link between low-grade inflammation and the presence of LVDD. In COPD, high levels of Tn-C are related to LVDD type-II.
authors.affiliation: Department of Pulmonary Medicine, Bellvitge University Hospital, Barcelona, Spain.|Pneumology Research Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: López-Sánchez
authors.affiliation: Department of Pulmonary Medicine, Bellvitge University Hospital, Barcelona, Spain.|Pneumology Research Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Mariana
authors.initials: M
authors.lastname: Muñoz-Esquerre
authors.affiliation: Department of Pulmonary Medicine, Bellvitge University Hospital, Barcelona, Spain.|Pneumology Research Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Huertas
authors.affiliation: Pneumology Research Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.|CIBERES, Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Montes
authors.affiliation: Department of Pulmonary Medicine, Bellvitge University Hospital, Barcelona, Spain.|Pneumology Research Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.|CIBERES, Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Molina-Molina
authors.affiliation: Department of Pulmonary Medicine, Bellvitge University Hospital, Barcelona, Spain.|Pneumology Research Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Manresa
authors.affiliation: Department of Pulmonary Medicine, Bellvitge University Hospital, Barcelona, Spain.|Pneumology Research Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.|CIBERES, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Dorca
authors.affiliation: Department of Pulmonary Medicine, Bellvitge University Hospital, Barcelona, Spain.|Pneumology Research Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.|CIBERES, Barcelona, Spain.
authors.forename: Salud
authors.initials: S
authors.lastname: Santos
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003430:Cross-Sectional Studies; D015150:Echocardiography, Doppler / Q000379:methods; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D009765:Obesity / Q000097:blood; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology; D012129:Respiratory Function Tests / Q000379:methods; D019063:Tenascin / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D000070857:Walk Test / Q000379:methods
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D019063:Tenascin; D002097:C-Reactive Protein; D020780:Matrix Metalloproteinase 9
keywords: COPD; extracellular matrix proteins; inflammatory biomarkers; left ventricular diastolic function; tenascin-C