Increased TIMP/MMP ratio in varicose veins: a possible explanation for extracellular matrix accumulation

Primary varicose veins are functionally characterized by venous back‐flow and blood stagnation in the upright position. Dilatation and tortuosity provide evidence for progressive venous wall remodelling, with disturbance of smooth muscle cell/extracellular matrix organization. Affected areas are not uniformly distributed, some areas being hypertrophic, whereas others are atrophic or unaffected. In 12 varicose veins and ten control veins, the proteolytic enzyme/inhibitor balance which may participate in the remodelling of the venous wall was investigated. For this purpose, the presence and enzymatic activity of matrix metalloproteinases (MMP‐2, MMP‐9), tissue inhibitors of MMPs (TIMP‐1, TIMP‐2), urokinase‐type (uPA) and tissue‐type (tPA) plasminogen activators (PAs), and plasminogen activator inhibitor‐1 (PAI‐1) were quantified by western blot and gelatin or plasminogen–casein zymography. In addition, MMP‐2, TIMP‐1, TIMP‐2, and PAI‐1 levels were measured by ELISA. A high TIMP‐1 level and a low MMP‐2 level/activity were found in varicose veins (p