Display options
Cite
Lemkens P, Boari G, Fazzi G, et al. Thrombospondin-1 in early flow-related remodeling of mesenteric arteries from young normotensive and spontaneously hypertensive rats. Open Cardiovasc Med J. 2012;6:50-9doi: 10.2174/1874192401206010050.
Lemkens, P., Boari, G., Fazzi, G., Janssen, G., Murphy-Ullrich, J., Schiffers, P., & De Mey, J. (2012). Thrombospondin-1 in early flow-related remodeling of mesenteric arteries from young normotensive and spontaneously hypertensive rats. The open cardiovascular medicine journal, 650-9. https://doi.org/10.2174/1874192401206010050
Lemkens, P, et al. "Thrombospondin-1 in early flow-related remodeling of mesenteric arteries from young normotensive and spontaneously hypertensive rats." The open cardiovascular medicine journal vol. 6 (2012): 50-9. doi: https://doi.org/10.2174/1874192401206010050
Lemkens P, Boari G, Fazzi G, Janssen G, Murphy-Ullrich J, Schiffers P, De Mey J. Thrombospondin-1 in early flow-related remodeling of mesenteric arteries from young normotensive and spontaneously hypertensive rats. Open Cardiovasc Med J. 2012;6:50-9. doi: 10.2174/1874192401206010050. Epub 2012 May 18. PMID: 22670160; PMCID: PMC3367304.
Copy Download .nbib Format: NLM
Share it on

Open Cardiovasc Med J. 2012;6:50-9. doi: 10.2174/1874192401206010050. Epub 2012 May 18.

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

The open cardiovascular medicine journal

P Lemkens, Gem Boari, Ge Fazzi, Gmj Janssen, Je Murphy-Ullrich, Pmh Schiffers, Jgr De Mey

Affiliations

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

PMID: 22670160 PMCID: PMC3367304 DOI: 10.2174/1874192401206010050

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.

Keywords: Arterial remodeling; eNOS; experimental hypertension; gene-expression; guanylyl cyclase; protein kinase G; resistance arteries; thrombospondin-1.

References

  1. J Cell Biol. 2003 Jun 23;161(6):1179-89 - PubMed
  2. Am J Physiol. 1989 Dec;257(6 Pt 2):H1958-65 - PubMed
  3. J Vasc Res. 2004 May-Jun;41(3):277-90 - PubMed
  4. Physiology (Bethesda). 2009 Feb;24:45-57 - PubMed
  5. J Biol Chem. 1993 Dec 15;268(35):26784-9 - PubMed
  6. Hypertension. 1996 Sep;28(3):505-6 - PubMed
  7. Circ Res. 2005 Jan 7;96(1):119-26 - PubMed
  8. Hypertension. 2005 Mar;45(3):432-7 - PubMed
  9. Am J Physiol Heart Circ Physiol. 2002 Jul;283(1):H146-55 - PubMed
  10. Am J Physiol. 1997 Oct;273(4):H1699-706 - PubMed
  11. J Cell Sci. 2003 Jul 15;116(Pt 14):2917-27 - PubMed
  12. Anal Biochem. 1985 Oct;150(1):76-85 - PubMed
  13. Am J Physiol Regul Integr Comp Physiol. 2003 Jan;284(1):R1-12 - PubMed
  14. J Clin Invest. 2006 May;116(5):1284-91 - PubMed
  15. Science. 1986 Jan 24;231(4736):405-7 - PubMed
  16. Front Biosci. 2006 Jan 01;11:356-67 - PubMed
  17. Physiol Rev. 1995 Jul;75(3):519-60 - PubMed
  18. Circ Res. 1998 Feb 9;82(2):139-46 - PubMed
  19. Microcirculation. 2002 Oct;9(5):343-51 - PubMed
  20. Nature. 1999 Jun 10;399(6736):601-5 - PubMed
  21. J Vasc Surg. 2003 Jul;38(1):147-54 - PubMed
  22. Annu Rev Pharmacol Toxicol. 1994;34:173-90 - PubMed
  23. J Cell Sci. 1996 Oct;109 ( Pt 10):2499-508 - PubMed
  24. Circulation. 2003 Nov 4;108(18):2230-5 - PubMed
  25. Microcirculation. 2001 Jun;8(3):195-206 - PubMed
  26. Arterioscler Thromb Vasc Biol. 2000 Sep;20(9):2057-63 - PubMed
  27. J Vasc Res. 2004 Mar-Apr;41(2):174-82 - PubMed
  28. Arterioscler Thromb Vasc Biol. 2007 Feb;27(2):317-24 - PubMed
  29. Am J Physiol Lung Cell Mol Physiol. 2001 Aug;281(2):L369-76 - PubMed
  30. FASEB J. 1991 Jun;5(9):2267-73 - PubMed
  31. J Biol Chem. 2004 Nov 5;279(45):46631-6 - PubMed
  32. Circ Res. 2001 Jul 20;89(2):180-6 - PubMed
  33. J Pharmacol Exp Ther. 2008 Mar;324(3):930-7 - PubMed
  34. Am J Physiol. 1994 Nov;267(5 Pt 1):C1405-13 - PubMed
  35. Circ Res. 1996 Nov;79(5):1015-23 - PubMed
  36. Circ Res. 2003 Jul 25;93(2):96-105 - PubMed
  37. Arterioscler Thromb Vasc Biol. 2003 Oct 1;23(10):1826-32 - PubMed
  38. Am J Physiol Heart Circ Physiol. 2000 Apr;278(4):H1233-40 - PubMed
  39. Arterioscler Thromb Vasc Biol. 1996 Oct;16(10):1256-62 - PubMed
  40. Hypertension. 2000 Jan;35(1 Pt 2):231-6 - PubMed
  41. Circ Res. 2003 Nov 28;93(11):1034-46 - PubMed
  42. Circ Res. 2003 Nov 14;93(10):907-16 - PubMed
  43. News Physiol Sci. 2002 Jun;17:105-9 - PubMed
  44. Am J Physiol Heart Circ Physiol. 2001 Sep;281(3):H1380-9 - PubMed
  45. Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1022-7 - PubMed
  46. J Clin Invest. 2001 Apr;107(7):785-90 - PubMed
  47. J Soc Gynecol Investig. 2004 Jul;11(5):304-10 - PubMed
  48. Arterioscler Thromb. 1992 Apr;12(4):519-28 - PubMed

Publication Types