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Smooth muscle cell elastase, atherosclerosis, and abdominal aortic aneurysms
J R Cohen1, I Sarfati, D Danna
1Department of Surgery, Long Island Jewish Medical Center, New Hyde Park, New York 11042.
Abstract:
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.
Insights
Smooth muscle cells (SMCs) secrete elastase in response to elastin peptides. Abdominal aortic aneurysm (AAA) patient SMCs show a higher elastase response, suggesting a role in atherosclerosis progression.
Area of Science:
- Vascular Biology
- Biochemistry
- Cell Biology
Background:
- Smooth muscle cells (SMCs) play a critical role in vascular health.
- Atherosclerosis, including abdominal aortic aneurysm (AAA), involves complex cellular processes.
- Elastin degradation products are implicated in vascular disease.
Purpose of the Study:
- To investigate elastase secretion by human aortic SMCs.
- To determine the effect of elastin-derived peptides (EDP) and low-density lipoproteins (LDL) on SMC elastase activity.
- To compare elastase secretion in SMCs from patients with AAA, aortic occlusive disease (AOD), and healthy controls.
Main Methods:
- Human aortic explants from AAA patients, AOD patients, and controls were cultured.
- Specimens were treated with medium alone, EDP, or LDL.
- Elastase activity in 4-week-old cultures was measured.
Main Results:
- Younger control aortas showed higher baseline elastase secretion.
- EDP significantly increased elastase secretion in all groups.
- AAA patient SMCs exhibited a significantly higher increase in elastase secretion in response to EDP compared to AOD or controls.
- LDL had no significant effect on SMC elastase secretion.
Conclusions:
- Aortic SMCs secrete elastase in response to EDP.
- SMC elastase secretion is age-dependent.
- AAA SMCs secrete abnormally high amounts of elastase in response to elastin breakdown products, potentially contributing to atherosclerosis.