Metalloproteinase-9 in circulating monocytes in pulmonary hypertension

The role of matrix metalloproteinases (MMPs) in pulmonary hypertension (PH) is complex as MMPs are involved in both the vascular and cardiac remodelling associated with PH. To gain insight into this problem, monocytes were isolated from pulmonary arterial blood in patients suffering from PH, related to chronic obstructive pulmonary disease (n = 6), chronic pulmonary thromboembolism (n = 3) or pulmonary arterial hypertension (n = 8). The severity of PH was associated with decreases in cardiac index (CI) and mixed venous blood oxygen saturation (SvO(2)), and an increase in right atrial pressure ((P) over bar (ra)). Monocyte pro-MMP-9 content (zymography) was positively correlated with SvO(2) (r = 0.73, P < 0.05) and CI (r = 0.66, P < 0.05), and negatively with (P) over bar (ra) (r = 0.54, P < 0.05); there was no significant correlation with pulmonary vascular resistance. In conclusion, the pro-MMP-9 content of circulating monocytes was lower in the more severe forms of PH which showed heart failure suggesting that such MMP enzymatic activity reflects heart failure following pulmonary vascular and myocardial remodelling in PH.