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Soluble factors modulate changes in collagen gene expression in abdominal aortic aneurysms
D J Minion1, Y Wang, T G Lynch
1Department of Surgery, University of Nebraska Medical Center, Omaha 68198.
Surgery
|August 1, 1993
Summary
Abdominal aortic aneurysm (AAA) tissue shows increased procollagen gene expression compared to normal and atherosclerotic occlusive disease (AOD) tissues. Paracrine factors, not autocrine, likely drive this AAA procollagen increase.
Area of Science:
- Vascular Biology
- Molecular Biology
- Biochemistry
Background:
- Procollagen gene expression and synthesis are implicated in abdominal aortic aneurysm (AAA) progression.
- Factors modulating procollagen expression in AAA and its specificity compared to atherosclerotic occlusive disease (AOD) remain unknown.
- Investigating paracrine versus autocrine signaling is crucial for understanding AAA pathogenesis.
Purpose of the Study:
- To quantify 1 alpha (I) procollagen messenger RNA levels in normal, AOD, and AAA tissues.
- To determine if procollagen gene expression differences are transferable to smooth muscle cells (SMC) via conditioned media.
- To elucidate the role of paracrine factors in AAA-associated procollagen expression.
Main Methods:
- Tissue samples (normal, AOD, AAA) were used for RNA extraction.
- Tissues were incubated in serum-free media to create conditioned media.
- Conditioned media were applied to primary human aortic smooth muscle cells (SMC) for 36 hours.
- Northern and dot blot analyses quantified 1 alpha (I) procollagen mRNA levels in tissues and SMC.
Main Results:
- 1 alpha (I) procollagen levels were significantly increased in AAA tissue (0.53 +/- 0.07) compared to normal (0.17 +/- 0.03) and AOD (0.23 +/- 0.05) tissues.
- SMC exposed to conditioned media from AAA tissue showed increased 1 alpha (I) procollagen levels (1.73 +/- 0.15) compared to those exposed to AOD (1.10 +/- 0.12) or normal (1.16 +/- 0.16) conditioned media.
- AOD tissue did not exhibit increased procollagen gene expression compared to normal tissue.
Conclusions:
- Atherosclerotic occlusive disease (AOD) does not show increased procollagen gene expression.
- The transfer of gene expression patterns via conditioned media suggests paracrine factors modulate procollagen expression in AAA.
- These findings highlight the importance of paracrine signaling in the pathogenesis of abdominal aortic aneurysms.