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Thrombospondin-1 in early flow-related remodeling of mesenteric arteries from young normotensive and spontaneously hypertensive rats.

Lemkens P, Boari G, Fazzi G, Janssen G, Murphy-Ullrich J, Schiffers P, De Mey J - Open Cardiovasc Med J (2012)

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Changes in protein expression of eNOS (A), sGCα1 (B), PKG1β (C), MMP2 (pro/act, D/E) and TSP1 (F), in mesenteric smallarteries exposed for 32 and 40 hours to normal (black bars), increased (hatched bars) or reduced (crosshatched bars) blood flow in 6 week oldWKY and SHR rats in vivo. Means ± SEM (n = 6). *p<0.05 versus NF.
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Figure 3: Changes in protein expression of eNOS (A), sGCα1 (B), PKG1β (C), MMP2 (pro/act, D/E) and TSP1 (F), in mesenteric smallarteries exposed for 32 and 40 hours to normal (black bars), increased (hatched bars) or reduced (crosshatched bars) blood flow in 6 week oldWKY and SHR rats in vivo. Means ± SEM (n = 6). *p<0.05 versus NF.

Mentions: Fig. (3) summarizes changes in protein expression in MA exposed for 32 (left panel) and 40 hours (right panel) to altered blood flow in vivo. These time-points were chosen to allow protein synthesis to occur and are based on the 24 hour gene expression experiments and the earlier observation that in low flow conditions specifically, the inward remodeling response manifests within 2 days [14]. In both HF and LF arteries of WKY and SHR rats, the protein levels of eNOS, sGCα1, PKG1β and MMP2 (pro/act) were not significantly altered after 32 and 40 hours of flow modifying surgery (Fig. 3A-E). Protein expression for TSP1 was significantly increased in LF arteries of both WKY and SHR (Fig. 3F). After 40 hours of exposure to LF, protein expression of TSP1 was below threshold in NF, HF and LF arteries.


Thrombospondin-1 in early flow-related remodeling of mesenteric arteries from young normotensive and spontaneously hypertensive rats.

Lemkens P, Boari G, Fazzi G, Janssen G, Murphy-Ullrich J, Schiffers P, De Mey J - Open Cardiovasc Med J (2012)

Changes in protein expression of eNOS (A), sGCα1 (B), PKG1β (C), MMP2 (pro/act, D/E) and TSP1 (F), in mesenteric smallarteries exposed for 32 and 40 hours to normal (black bars), increased (hatched bars) or reduced (crosshatched bars) blood flow in 6 week oldWKY and SHR rats in vivo. Means ± SEM (n = 6). *p<0.05 versus NF.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3367304&req=5

Figure 3: Changes in protein expression of eNOS (A), sGCα1 (B), PKG1β (C), MMP2 (pro/act, D/E) and TSP1 (F), in mesenteric smallarteries exposed for 32 and 40 hours to normal (black bars), increased (hatched bars) or reduced (crosshatched bars) blood flow in 6 week oldWKY and SHR rats in vivo. Means ± SEM (n = 6). *p<0.05 versus NF.
Mentions: Fig. (3) summarizes changes in protein expression in MA exposed for 32 (left panel) and 40 hours (right panel) to altered blood flow in vivo. These time-points were chosen to allow protein synthesis to occur and are based on the 24 hour gene expression experiments and the earlier observation that in low flow conditions specifically, the inward remodeling response manifests within 2 days [14]. In both HF and LF arteries of WKY and SHR rats, the protein levels of eNOS, sGCα1, PKG1β and MMP2 (pro/act) were not significantly altered after 32 and 40 hours of flow modifying surgery (Fig. 3A-E). Protein expression for TSP1 was significantly increased in LF arteries of both WKY and SHR (Fig. 3F). After 40 hours of exposure to LF, protein expression of TSP1 was below threshold in NF, HF and LF arteries.

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus