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Endothelin‐1 Expression In Vascular Adventitia
Author(s) -
Di Wang Hui,
Rätsep Matthew,
Nguyen Huy,
Adams Michael
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb695
Subject(s) - adventitia , losartan , endothelin receptor , endothelin 1 , angiotensin ii , aorta , immunocytochemistry , angiotensin ii receptor type 1 , receptor , vascular tissue , messenger rna , pathology , chemistry , endocrinology , biology , medicine , gene , biochemistry , botany
Background and hypothesis Emerging evidence indicates that the vascular adventitia is a dynamic tissue and may play a critical role in the development and progression of vascular disorders. Endothelin‐1 (ET‐1) is a potent vasoactive peptide, mediating both vascular contractile and growth responses. Endothelial cells are a major source of ET‐1, but the possibility that vascular adventitial fibroblasts generate ET‐1 has not been explored. We hypothesized that aortic adventitial fibroblasts have the ability to produce ET‐1. Methods For studies in cultured cells, vascular adventitial fibroblasts were isolated from the mouse (15 weeks of age) thoracic aorta and incubated with various concentrations of angiotensin II (Ang II). mRNA levels of preproET‐1 were detected by RT‐PCR. ET‐1 levels in the culture medium were measured by ELISA. In another set of study, after being anesthetized and euthanized by exsanguinations, the aortas were isolated, formalin fixed, embedded in paraffin, and then serially sectioned. The expressions of ET‐1 were determined by immunofluorescence staining. Results and Conclusion Ang II induced an increase in preproET‐1 mRNA levels and the immunoreactive peptide ET‐1 levels. The increases in preproET‐1 mRNA expression and ET‐1 release were blocked by Losartan, an AT1‐receptor antagonist but not PD123319 , an AT2‐receptor antagonist. In the aorta sections, although staining of ET‐1 was present throughout the vascular wall, the majority of its expression was observed in both the adventitial and endothelial layers. In conclusion, these findings demonstrate that the adventitia contributes to ET‐1 production which suggests the possibility for the adventitia to contribute to regulate vascular functions. We would like to acknowledge our granting agency the Heart and Stroke Foundation of Canada.