BACKGROUND: Changes in the proteoglycan metabolism of the intima of arteries belong to the initial lesions of atherosclerosis (AS). The accumulation of proteoglycans, alterations of pericellular glycoproteins and modulations of collagen turnover also play a fundamental role in the progression of AS. They influence lipid retention, cell behavior and calcinosis. The decisive role played by the matrix metalloproteinases (MMPs) and their inhibiting factors (tissue inhibitors of metalloproteinases [TIMPs]) in these processes is not yet fully understood and therefore the subject of this overview. The causes of the abrupt change of a long-term existing stabile AS to a vulnerable plaque as well as the participation of age-related vascular wall remodeling in the progression of AS also remain open questions. DISCUSSION: Apart from the well-known risk factors for AS, less well-known influences like the disturbances of gene expression in vascular smooth muscle cells affect an MMP/TIMP imbalance. The various consequences of this imbalance range from intima cell proliferation as an early change in AS as well as accelerated progression to the destabilization of fibrous plaques by increased collagenolysis as well as the formation of aneurysms. Infectious or toxic influences may trigger these mechanisms; an involvement of age-related vessel wall changes should also be considered. The prognostic significance of circulating MMP concentrations for the existence of instabile plaques are of great interest, as is the plaque stabilizing effect of statins by suppression of MMPs. CONCLUSIONS: MMPs navigate the behavior of vascular wall cells in different AS stages, in adaptive remodeling, in normal aging and in non-atherosclerotic vessel disease. The clinical relevance of a disturbance in the MMP/TIMP balance is demonstrated firstly by the initiation of AS due to migration and proliferation of intima cells and secondly in the collagenolysis, necrotic transformation and apoptosis of existing fibrous lesions resulting in instabile rupture proned plaques. Investigations into the genetic typing of MMPs and the results of experimental gene deficiency models have significantly contributed to the clarification of these facts. Copyright (c) 2007 S. Karger AG, Basel.
BACKGROUND: Changes in the proteoglycan metabolism of the intima of arteries belong to the initial lesions of atherosclerosis (AS). The accumulation of proteoglycans, alterations of pericellular glycoproteins and modulations of collagen turnover also play a fundamental role in the progression of AS. They influence lipid retention, cell behavior and calcinosis. The decisive role played by the matrix metalloproteinases (MMPs) and their inhibiting factors (tissue inhibitors of metalloproteinases [TIMPs]) in these processes is not yet fully understood and therefore the subject of this overview. The causes of the abrupt change of a long-term existing stabile AS to a vulnerable plaque as well as the participation of age-related vascular wall remodeling in the progression of AS also remain open questions. DISCUSSION: Apart from the well-known risk factors for AS, less well-known influences like the disturbances of gene expression in vascular smooth muscle cells affect an MMP/TIMP imbalance. The various consequences of this imbalance range from intima cell proliferation as an early change in AS as well as accelerated progression to the destabilization of fibrous plaques by increased collagenolysis as well as the formation of aneurysms. Infectious or toxic influences may trigger these mechanisms; an involvement of age-related vessel wall changes should also be considered. The prognostic significance of circulating MMP concentrations for the existence of instabile plaques are of great interest, as is the plaque stabilizing effect of statins by suppression of MMPs. CONCLUSIONS: MMPs navigate the behavior of vascular wall cells in different AS stages, in adaptive remodeling, in normal aging and in non-atherosclerotic vessel disease. The clinical relevance of a disturbance in the MMP/TIMP balance is demonstrated firstly by the initiation of AS due to migration and proliferation of intima cells and secondly in the collagenolysis, necrotic transformation and apoptosis of existing fibrous lesions resulting in instabile rupture proned plaques. Investigations into the genetic typing of MMPs and the results of experimental gene deficiency models have significantly contributed to the clarification of these facts. Copyright (c) 2007 S. Karger AG, Basel.