title: Neutrophil proteolytic activation cascades: a possible mechanistic link between chronic periodontitis and coronary heart disease.
abstract: Cardiovascular diseases are chronic inflammatory diseases that affect a large segment of society. Coronary heart disease (CHD), the most common cardiovascular disease, progresses over several years and affects millions of people worldwide. Chronic infections may contribute to the systemic inflammation and enhance the risk for CHD. Periodontitis is one of the most common chronic infections that affects up to 50% of the adult population. Under inflammatory conditions the activation of endogenous degradation pathways mediated by immune responses leads to the release of destructive cellular molecules from both resident and immigrant cells. Matrix metalloproteinases (MMPs) and their regulators can activate each other and play an important role in immune response via degrading extracellular matrix components and modulating cytokines and chemokines. The action of MMPs is required for immigrant cell recruitment at the site of inflammation. Stimulated neutrophils represent the major pathogen-fighting immune cells that upregulate expression of several proteinases and oxidative enzymes, which can degrade extracellular matrix components (e.g. MMP-8, MMP-9 and neutrophil elastase). The activity of MMPs is regulated by endogenous inhibitors and/or candidate MMPs (e.g. MMP-7). The balance between MMPs and their inhibitors is thought to mirror the proteolytic burden. Thus, neutrophil-derived biomarkers, including myeloperoxidase, may activate proteolytic destructive cascades that are involved in subsequent immune-pathological events associated with both periodontitis and CHD. Here, we review the existing studies on the contribution of MMPs and their regulators to the infection-related pathology. Also, we discuss the possible proteolytic involvement and role of neutrophil-derived enzymes as an etiological link between chronic periodontitis and CHD.
authors.affiliation: Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Hatem
authors.initials: H
authors.lastname: Alfakry
authors.affiliation: Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.
authors.forename: Ernst
authors.initials: E
authors.lastname: Malle
authors.affiliation: Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.
authors.forename: Chintan N
authors.initials: CN
authors.lastname: Koyani
authors.affiliation: Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland pirkko.pussinen@helsinki.fi.
authors.forename: Pirkko J
authors.initials: PJ
authors.lastname: Pussinen
authors.affiliation: Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Timo
authors.initials: T
authors.lastname: Sorsa
mesh_terms: D000328:Adult; D000818:Animals; D002908:Chronic Disease; D055113:Chronic Periodontitis / Q000150:complications / Q000276:immunology*; D003327:Coronary Disease / Q000209:etiology / Q000276:immunology*; D006801:Humans; D007239:Infections / Q000150:complications / Q000276:immunology*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000502:physiology*; D059748:Proteolysis; D012306:Risk
chemical_list: D020782:Matrix Metalloproteinases
keywords: Aggregatibacter actinomycetemcomitans; Porphyromonas gingivalis; cardiovascular disease; coronary artery disease; gingival crevicular fluids; hypochlorous acid; lipopolysaccharide; matrix metalloproteinases; myeloperoxidase; neutrophils; oral infections; periodontal diseases; tissue inhibitor of matrix metalloproteinases