Influence of homocysteine on matrix metalloproteinase-2: activation and activity.

Increased levels of the physiological amino acid homocysteine (Hcy) are considered a risk factor for vascular disease. Hyperhomocysteinemia causes an intense remodelling of the extracellular matrix in arterial walls, particularly an elastolysis involving metalloproteinases. We investigated the activation of the latent elastolytic metalloproteinase proMMP-2 (72 kDa) by Hcy.

Hyperhomocysteinemia induces elastolysis in minipig arteries: structural consequences, arterial site specificity and effect of captopril-hydrochlorothiazide.

Hyperhomocysteinemia is a risk factor for arterial diseases, and the deterioration of the arterial elastic structures is one of the possible mechanisms underlying this epidemiological association. The aim of this paper is to quantitatively characterize such structural alterations and to explore their causes in a previous model of dietary induced mild hyperhomocysteinemia in minipigs. After four months, both a morphodensitometrical analysis of the elastic structure and a biochemical analysis of elastin and elastase activities were performed on the infrarenal abdominal aorta (IRAA) and the proximal left interventricular coronary artery (LIVCA) of control (C), hyperhomocysteinemic (H) and captopril-hydrochlorothiazide (Cp-Htz, 25 + 12.

Medial elastic structure alterations in atherosclerotic arteries in minipigs: plaque proximity and arterial site specificity.

Using a model of atherosclerosis in minipigs, we analyzed changes in elastic structure within the medial sections of the abdominal aorta and left interventricular coronary artery both in the vicinity of and distal to atheromatous plaques. Twenty-four animals, divided into three groups, were fed either a control diet or a hypercholesterolemic and hyperhomocysteinic atherogenic diet, alone or in association with an antihypertensor, namely isosorbide dinitrate (Risordan). The atherogenic diet, administered for a period of four months, induced in the minipig advanced noncalcified atherosclerotic lesions that were histologically similar to those found in humans.

Therapeutic effects of nitric oxide-donor isosorbide dinitrate on atherosclerosis-induced alterations in hemodynamics and arterial viscoelasticity are independent of the wall elastic component.

Whether the arterial elastic structures are involved in the beneficial effects of long-term treatment with organic nitrates on atherosclerosis-induced changes in hemodynamics and arterial wall viscoelastic properties, are case for angiotensin-converting enzyme (ACE) inhibitors, is not known. In the present study, atherogenic (A) diet, and isosorbide dinitrate (ISDN) (I) (60 mg Risordan LP, daily dose) were given concomitantly for 4 months to adult Pitman-Moore minipigs (A + I animals, n = 8), which were compared with A (n = 8) or control (C, n = 8) animals. Blood flow was investigated by hemodynamics in the hindlimb arterial bed; and wall rheology, histomorphometry and elastin; and desmosine (DES) and isodesmosine (IDE) contents in the abdominal aorta.