A new serum proteolytic enzyme in aneurysm pathogenesis.
Despite significant progress in elucidating the pathogenesis of aneurysmal disease, the precise etiology of arterial wall degradation remains unclear. Numerous etiologies have been implicated, including stress-strain factors, structural wall abnormalities, and enzyme imbalance. We have previously shown that collagenase and elastase are increased in aortic aneurysm tissue. Herein we report and characterize a newly described serum compound that is able to hydrolyze an artificial elastase substrate but is not elastase. This substance is elevated in patients with atherosclerotic disease and, following aneurysmectomy, its concentration increases by threefold. Examination of the substance reveals that it is bound to lipid and consists of four subunits of molecular weights: 310,000, 62,000, 40,000, and 10,000 daltons. It has characteristics of thiol, carboxyl, and metalloenzymes and is most active at a pH of 7.0 to 8.0. A relationship between this serum compound and aneurysm tissue enzymatic activity is noted. We postulate that this serum compound may be produced by mononuclear cells and released into the serum. Furthermore, monocytes may enter the arterial wall intima and release this substance, resulting in proteolytic arterial wall degradation and subsequent aneurysm formation.
D001014:Aortic Aneurysm / Q000201:enzymology* / Q000209:etiology; D001018:Aortic Diseases / Q000201:enzymology; D001157:Arterial Occlusive Diseases / Q000201:enzymology*; D001798:Blood Proteins / Q000302:isolation & purification; D002340:Carotid Artery Diseases / Q000201:enzymology; D004549:Elastin / Q000378:metabolism; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007962:Leukocytes / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009000:Monocytes / Q000201:enzymology; D009504:Neutrophils / Q000201:enzymology; D010196:Pancreatic Elastase / Q000378:metabolism; D010447:Peptide Hydrolases / Q000097:blood* / Q000302:isolation & purification; D011509:Proteoglycans
D001798:Blood Proteins; D011509:Proteoglycans; C042057:proteolysis-inducing peptide; D004549:Elastin; D010447:Peptide Hydrolases; D010196:Pancreatic Elastase