title: The dynamic extracellular matrix: intervention strategies during heart failure and atherosclerosis.
abstract: The extracellular matrix is no longer seen as the static embedding in which cells reside; it has been shown to be involved in cell proliferation, migration and cell-cell interactions. Turnover of the different extracellular matrix components is an active process with multiple levels of regulation. Collagen, a major extracellular matrix constituent of the myocardium and the arterial vascular wall, is synthesized by (myo)fibroblasts in the myocardium and smooth muscle cells in the medial arterial vascular wall. Its degradation is controlled by proteinases, which include matrix metalloproteinases. This review will focus on the impact of fibrosis and especially collagen turnover on the progression of heart failure and atherosclerosis, two of the main cardiovascular pathologies. We will discuss data from human studies and animal models, with an emphasis on the effects of interventions on collagen synthesis and degradation. We conclude that there is a dynamic (dis)balance in the rate of collagen synthesis and degradation during heart failure and atherosclerosis, which makes the outcome of interventions not always predictable. Alternative approaches for intervening in collagen metabolism will be discussed as possible therapeutic intervention strategies.
authors.affiliation: Department of Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, 6200 MD Maastricht, The Netherlands.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Heeneman
authors.forename: Jack P
authors.initials: JP
authors.lastname: Cleutjens
authors.forename: Birgit C
authors.initials: BC
authors.lastname: Faber
authors.forename: Esther E
authors.initials: EE
authors.lastname: Creemers
authors.forename: Robert-Jan
authors.initials: RJ
authors.lastname: van Suylen
authors.forename: Esther
authors.initials: E
authors.lastname: Lutgens
authors.forename: Kitty B
authors.initials: KB
authors.lastname: Cleutjens
authors.forename: Mat J
authors.initials: MJ
authors.lastname: Daemen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D003094:Collagen / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000378:metabolism*; D003331:Coronary Vessels; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D016032:Randomized Controlled Trials as Topic; D011973:Receptors, LDL / Q000037:antagonists & inhibitors; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors
chemical_list: D000960:Hypolipidemic Agents; D011973:Receptors, LDL; D016212:Transforming Growth Factor beta; D003094:Collagen; D020782:Matrix Metalloproteinases