To test the hypothesis that elastin-derived peptides (EDP) from human aortic tissue may be chemotactic for inflammatory cells, we studied the chemotaxis of neutrophils and monocytes to EDP derived from abdominal aortic aneurysm (AAA), aortic occlusive disease (AOD), and control aortas. In addition, we determined if neutrophils deliver neutrophil elastase to the aorta in vivo by staining for neutrophil elastase (NE) throughout the course of abdominal aortic aneurysms with the monoclonal antibody to human NE. EDP from AAA, AOD, and control tissue demonstrated significant chemotactic activity for both neutrophils and monocytes. All neutrophils had a greater attraction to EDP from AAA tissue compared to AOD and control aorta. Neutrophils from AAA patients were more attracted to EDP of AAA tissue than were neutrophils of AOD or control patients attracted to their respective aortic EDP. Neutrophil elastase stained positive in the adventitia and thrombus throughout the course of the aneurysm, but was not found in the intima, media, or plaque of the aorta.
Smooth muscle cells (SMC) were obtained by outgrowth of human aortic explants from abdominal aortic aneurysm (AAA) patients, aortic occlusive disease (AOD) patients, and transplant donors (controls). Specimens were incubated with medium alone or medium with either elastin-derived peptides (EDP, 5 micrograms/mL) or low-density lipoproteins (LDL, 5 micrograms/mL). Elastase activity (ng/mg total protein) was assayed from 4-week-old cultures. Control aortas obtained from patients significantly younger secrete an increased amount of elastase at baseline compared with AOD and AAA patients (p less than 0.05). Elastin-derived peptides caused a significant increase in elastase secretion in all groups. The increase in elastase secretion in response to EDP in AAA patients was significantly higher compared with AOD or control. Low-density lipoprotein had no effect on SMC elastase secretion. These data suggest that (1) aortic SMCs secrete elastase in response to EDP, (2) SMC elastase is age dependent, and (3) AAA SMC secrete an abnormally high amount of elastase compared with AOD and control aortas in response to EDP. Like the neutrophil, the SMC is highly responsive to the degradation products of elastin and in AAA patients secrete significantly increased amounts of elastase in response to the breakdown products of atherosclerosis.
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