A new serum proteolytic enzyme in aneurysm pathogenesis

Abstract

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. (J VAsc SugG 1985; 2:393-9.

Response of plasma matrix metalloproteinase-9 to conventional abdominal aortic aneurysm repair or endovascular exclusion: Implications for endoleak

“…Investigations of aneurysms have sought to identify a biologically relevant marker of the disease process. 8,[12][13][14] Since Busuttil et al 15 described the role of elastase in aneurysm formation and later characterized a soluble metalloelastase, 3 significant progress has been made in isolating and describing matrix metalloproteinases and in elucidating their role in the development of arterial aneurysms. [16][17][18] MMP-9 has been shown to be the principle elastase within the aneurysmal aortic wall and is expressed by macrophages in excess when compared with other metalloproteinases.…”

“…2 Matrix metalloproteinases are soluble, zinc-dependent enzymes produced by macrophages and smooth muscle cells that are capable of breaking down components of the extracellular matrix and have been implicated by many investigators in the development of aneurysm formation. [3][4][5][6] Matrix metalloproteinase-9 (MMP-9) has elastolytic activity that may act in concert with proteases and other metalloproteinases to affect structural arterial changes in aneurysmal disease. 7 Elevated MMP-9 levels in aortic aneurysmal tissue, and in that patient plasma, have been shown.…”

Surgery of the Thoracic Aorta

“…Abnormal proteolysis, the presence of elastolytic serum enzymes, and deficiencies of collagen and elastin have been implicated as factors contributing to the development of these aneurysms. [23][24][25][26][27] Although atheromatous changes are frequently present in and around such aneurysms, the causative role of atherosclerosis in their development is not clearly established. 20,28 Aneurysms resulting from blunt trauma most frequently involve the proximal descending thoracic aorta.…”