The pathogenesis of hyaline arteriolosclerosis.
Although hyaline arteriolosclerosis is very common and has been of interest to pathologists for well over 100 years, its pathogenesis has never been determined. This study demonstrates that iC3b bound via an ester linkage to hydroxyl groups on the repeating disaccharide units of hyaluronic acid is a major component of arteriolar hyaline. The deposition of iC3b within the walls of arterioles appears to be due to slow spontaneous activation of the alternative complement pathway and random binding of metastable C3b to proximate hyaluronic acid within the arteriolar wall. Since hyaluronic acid does not activate the alternative complement pathway, bound C3b is rapidly inactivated by factors I and H to iC3b, which, along with factor H, remains bound to hyaluronic acid. The hyaline in some hyalinized arterioles also contains IgM and early and late classical complement pathway components. Indirect evidence suggests that the IgM represents immunoconglutinin, an autoantibody to neoantigens on iC3b and that their interaction results in activation of the classical complement pathway. The gradual accumulation of iC3b, factor H, and, at times, IgM and classical complement pathway components within the walls of arterioles is considered to be a physiologic consequence of aging and probably cannot be prevented, because interruption of the initial binding of metastable C3b to hyaluronic acid would require abrogation of the critically important functions of the alternative complement pathway.
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Gamble
D000293:Adolescent; D000328:Adult; D000368:Aged; D001160:Arterioles / Q000378:metabolism; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D003180:Complement C3b Inactivator Proteins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D006818:Hyalin / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D013154:Spleen / Q000098:blood supply
D003180:Complement C3b Inactivator Proteins; D007075:Immunoglobulin M; D006820:Hyaluronic Acid