Pathogenesis of rheumatoid arthritis: a vascular hypothesis.
Past research into the pathogenesis of RA has generally concerned itself with established inflammation. The present review summarizes alterations in microvascular anatomy and function which occur during the hypoxic state, in various experimental and disease conditions. It further shows that tissue hypoxia is a common finding in RA and that the microvascular alterations of RA are similar to those produced by experimental hypoxia. The available data suggest that microcirculatory compromise, concomitant with an increase in metabolic needs of synovial tissue, may initiate tissue injury via anoxia and acidosis, resulting in hydrolytic enzyme release, increased vascular permeability and acceleration of inflammatory processes. It is further believed that the microcirculatory abnormality may be generalized, accounting for the systemic manifestations often seen in RA. Factors effecting arteriolar blood flow obstruction are reviewed to identify areas for future investigation in RA and other disorders involving microvasculopathy. The multitude of longknown and newly recognized factors predisposing to vasospasm and vasodilatation have been outlined as a guide to possible mechanisms which may be operative in RA. An attempt has been made to gather and synthesize the available data in the hope that it may stimulate other investigators to pursue more definitive research into specific areas which may show early microvascular abnormalities in the pathophysiology of RA. Identification of factors operative early in the pathogenesis of RA, before it becomes self-perpetuating, may well be a step in the direction of preventing the ravages of this disease, or providing insight to more effective control.
D001160:Arterioles; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000209:etiology*; D001808:Blood Vessels / Q000502:physiology*; D002196:Capillaries / Q000033:anatomy & histology; D003251:Constriction, Pathologic; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology; D007136:Immunoglobulins / Q000502:physiology; D012217:Rheumatoid Factor / Q000276:immunology; D014652:Vascular Diseases / Q000150:complications / Q000209:etiology; D014699:Venules
D007136:Immunoglobulins; D012217:Rheumatoid Factor