Thrombospondin-1 in Early Flow-Related Remodeling of Mesenteric Arteries from Young Normotensive and Spontaneously Hypertensive Rats
P Lemkens1, GEM Boari2, GE Fazzi1, GMJ Janssen1, JE Murphy-Ullrich3, PMH Schiffers1, JGR De Mey1, *
Identifiers and Pagination:Year: 2012
First Page: 50
Last Page: 59
Publisher Id: TOCMJ-6-50
Article History:Received Date: 22/2/2012
Revision Received Date: 28/3/2012
Acceptance Date: 9/4/2012
Electronic publication date: 18/5/2012
Collection year: 2012
open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
We tested the hypotheses that TSP-1 participates in the initiation of remodeling of small muscular arteries in response to altered blood flow and that the N-terminal domain of TSP-1 (hepI) can reverse the pathological inward remodeling of resistance arteries from SHR.
We measured (1) changes in gene/protein expression in MA of 6 week old WKY and SHR exposed to either increased (+ 100 %) or reduced blood flow (- 90 %) for 24-40 hours and (2) structural changes in MA of 12 week old SHR exposed for 3 days to hepI in organ culture.
In both HF and LF of WKY, mRNA expression of eNOS, sGCα1 and PKG1β were significantly reduced (p < 0.05), whereas mRNA of TSP1 was markedly increased (p < 0.05). In MA of young SHR, similar results were obtained except that eNOS mRNA was not reduced in LF. Expression of TSP1 protein was significantly increased in LF of young WKY and SHR (p < 0.05). Exposure of MA of 12 week old SHR to hepI (1 µmol/L) resulted in a rapid lumen diameter increase (+ 12 ± 2% after 3 days) without alteration in vascular reactivity, distensibility, media surface area or cell number.
These are the first observations of reduced gene expression of eNOS/sGC/PKG and increased expression of TSP1 at the initiation of arterial remodeling in young WKY and SHR, irrespective of its outward or inward outcome. Furthermore, a fragment of TSP-1 rapidly and directly reversed pathological inward arterial remodeling of SHR in vitro.