P-198: Circulating monocyte metalloproteinase-9 content and severity of pulmonary hypertension

Arterial remodeling is known to be a major element in the etiology and severity of pulmonary hypertension (PH) and matrix metalloproteinases (MMP) are thought to be one of the determinant factors in such remodeling. A main source of MMPs is the circulating monocyte. We hypothesized, therefore, that circulating monocyte MMP-9 content could be used as a marker of the severity of PH. Hemodynamic severity is characterized by a decrease in cardiac index and in venous oxygen saturation, and an increase in right atrial pressure. A blood sample was taken during routine pulmonary artery catherisation. Monocytes were isolated by panning and cultured in cell culture medium. They were then lysed with acid buffer and MMP-9 content (expressed as pg.monocyte-1) determined by zymography on gelatin, using commercially available MMP-9 as standard. A group of fifteen patients with PH of varying severity were studied (7 cases of primary PH, 4 chronic pulmonary thrombo-embolism and 4 chronic obstructive pulmonary disease). There were no significant relationships between MMP-9 content and pulmonary arterial pressure or pulmonary vascular resistance. There were positive correlations between MMP-9 content and venous saturation in oxygen (slope = 0.029±0.008 %.pg-1.monocyte, P < 0.05, n = 15), and cardiac index (slope = 0.52±0.14 L.min-1.m-2.pg-1.monocyte, P < 0.05, n = 15). There was a negative correlation between MMP-9 content and right auricular pressure (slope = -0.038±0.014 mmHg.pg-1.monocyte, P < 0.05, n = 15). In conclusion, a decrease in circulating monocyte MMP-9 content may be a marker for the progression of PH. This may be explained by the role played by MMPs in pulmonary arterial remodeling.