Abstract
Chronic inflammatory disorders constitute a heterogenous group of complex and multifactorial diseases, which are often associated with increased cardiovascular morbidity and mortality, independent of the established cardiovascular risk factors. In keeping with this observation, hypercoagulability is frequently observed in patients suffering from atherosclerosis, chronic obstructive pulmonary disease and rheumatoid arthritis although the physiological significance of activated coagulation remained elusive. However, the identification of protease activated receptors (PAR) seems to provide a link between coagulation activation and disease progression as their activation by coagulation factors triggers a broad range of signaling pathways relevant for chronic inflammatory disorders. In experimental animal models, anticoagulation and/or genetic ablation of PAR signaling affords protection against the perpetuation of atherosclerosis, chronic obstructive pulmonary disease and rheumatoid arthritis. It is thus tempting to speculate that targeting the coagulation-PAR axis might have clinical relevance in the setting of chronic inflammatory disorders. In the current review, we discuss the current knowledge on coagulation activation in inflammatory disorders, we discuss the relationship between atherosclerosis, chronic obstructive pulmonary disease and rheumatoid arthritis and we review the current knowledge on PAR signaling in these disorders.
Keywords: Chronic inflammatory disorders, coagulation, inflammation, protease-activated receptors, atherosclerosis, chronic obstructive pulmonary diseas, rheumatoid arthritis, maresins, inter alia, eicosapen-taenoic acid, n-3, ApoE4 genotype, rotoxins, methylmercury, microcephaly, cerebral palsy, institutional boilers, chlo-rine production, waste incineration, oceans - bio-concentrate, sporadic, vitro nitrosamine, neurodegeneration, cadaverine, biogenic amine, amyloid, beta amyloid, amy-loidosis, DHA-oxygenation pathways, ASA-generated, acetylating COX-2, COX, arachidonic acid (ARA), resolvins, protect-ins, neuroprotectin D1 (NPD1, neurite growth, A pep-tide, brain-derived neurotrophic factor, superoxide dismutase-1, catalase, Reactive oxygen species, catecholamine synthesis, n-3 family, PUFAs, glial cells, astro-cytes, BDNF protein
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