Extracellular matrix turnover, angiogenesis and endothelial function in acute lung injury: relationship to pulmonary dysfunction and outcome

Acute lung injury (ALI) is a syndrome with a diagnostic criteria based on hypoxemia and a classical radiological appearance, with acute respiratory distress syndrome at the severe end of the disease. Facts recommended the occurrence of rupture of the basement membranes and interstitial matrix remodeling during ALI. Matrix metalloproteinases (MMPs) participate in tissue remodeling related with pathological conditions such as ALI. We hypothesized the interrelationships between extracellular matrix (ECM) turnover as MMP-9 and indicator of angiogenesis such as angiopoietin-2 (Ang-2) as well as plasma von Willebrand factor (vWF) and their correlation with arterial partial pressure of oxygen (PaO₂), oxygen saturation (SaO₂) and mortality in ALI/ARDS.

Eighty-eight mechanically ventilated patients (68 male, mean (SD) age 61 (10) years) were compared with 40 healthy controls (36 male, mean (SD) age 57 (10)). All biomarkers were measured by ELISA. Oxygenation, body temperature, leucocytes, and platelet counts were noted.

Plasma levels of all biomarkers were significantly different among ALI/ARDS subjects (P < 0.001) and they inversely related to PaO₂ and SaO₂ and positively related to mortality. Plasma levels of MMP-9 were negatively correlated with PaO₂ and SaO₂% in ALI/ARDS patients (r = - 0.75, P < 0.0001 and r = - 0.81, P < 0.0001) respectively. Plasma level of Ang-2 was negatively correlated with PaO₂ and SaO₂% in ALI/ARDS patients (r = - 0.68, P < 0.0001 and r = - 0.63, P < 0.0001) respectively. Plasma levels of vWF were negatively correlated with PaO₂ and SaO₂% in ALI/ARDS patients (r = - 0.76, P < 0.0001 and r = - 0.69, P < 0.001) respectively. Elevated plasma levels of all indices were interrelated at the first day of admission.