title: Proteolysis of the pericellular matrix: a novel element determining cell survival and death in the pathogenesis of plaque erosion and rupture.
abstract: The 2 major general concepts about the cell biology of atherogenesis, growth of smooth muscle cells, and lipid accumulation in macrophages, ie, foam cell formation, have not been able to satisfactorily explain the genesis of acute coronary syndromes. Rather, the basic pathology behind the acute atherothrombotic events relates to erosion and rupture of unstable coronary plaques. At the cellular level, we now understand that a switch from cellular growth to cellular death, notably apoptosis, could be involved in turning at least some types of atherosclerotic plaques unstable. Because intimal cells require a proper matrix environment for normal function and survival, the vulnerability of an atherosclerotic plaque may critically depend on the integrity of the pericellular matrix of the plaque cells. In vitro studies have revealed that plaque-infiltrating inflammatory cells, such as macrophages, T-lymphocytes, and mast cells, by secreting a variety of proteases capable of degrading pericellular matrix components, induce death of endothelial cells and smooth muscle cells, and so provide a mechanistic explanation for inflammation-dependent plaque erosion and rupture. Thus, a novel link between inflammation and acute coronary syndromes is emerging. For a more explicit understanding of the role of proteases released by inflammatory cells in the conversion of a clinically silent plaque into a dangerous and potentially killing plaque, animal models of plaque erosion and rupture need to be established.
authors.affiliation: Wihuri Research Institute, Helsinki, Finland.
authors.forename: Ken A
authors.initials: KA
authors.lastname: Lindstedt
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Leskinen
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
mesh_terms: D000818:Animals; D017209:Apoptosis; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D001808:Blood Vessels / Q000293:injuries; D002448:Cell Adhesion; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005355:Fibrosis; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications; D007694:Killer Cells, Natural / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D008407:Mast Cells / Q000502:physiology; D008955:Models, Cardiovascular; D009504:Neutrophils / Q000502:physiology; D010447:Peptide Hydrolases / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D011817:Rabbits; D012422:Rupture, Spontaneous; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology
chemical_list: D016326:Extracellular Matrix Proteins; D010982:Platelet-Derived Growth Factor; D010447:Peptide Hydrolases