본문 바로가기
KERD
논문KCI 등재

Laminar Shear Stress Protects Against Premature Endothelial Senescence by SIRT1-Dependent Mechanisms

0

조회

0

다운로드

0

인용

0

참고문헌

키워드

초록

PURPOSE:Accumulation of senescent endothelial cells (ECs) and development of vascular aging have been implicated in the etiology of vascular dysfunction and disease. Aerobic exercise has been recognized as the single most effective non-pharmacological anti-aging intervention via increased laminar shear stress (LSS). This study aimed to determine the protective effects of LSS against premature senescence and the underlying mechanism. METHODS: Carotid artery partial ligation surgery was performed on the left carotid arteries (LCAs) of C57BL/6J male mice to determine the effect of disturbed flow on the development of endothelial senescence. Senescence-associated β-galactosidase (SA-β-gal) staining was performed to measure cellular senescence. Expression levels of protein markers for cell senescence including p21, p16, and p53 were measured by western blotting. RESULTS: En face SA-β-gal staining was identified only in the partially ligated LCAs of voluntary wheel-running mice, suggesting a direct relevance of LSS on the prevention of vascular senescence. In the in vitro H2O2-induced premature senescence model, preconditioning of high-flow LSS (20 dyne/cm2 , 36 hours) induced significant reduction in the percentage of SA-β-gal positive ECs. Expression of the molecular markers of cellular senescence such as p21, p16, and p53 was significantly decreased by LSS pretreatment. However, the protective effects of LSS against premature senescence were completely abolished by SIRT1 inhibition. CONCLUSIONS: The results suggest that high-flow LSS has protective effects against oxidative stress-induced premature endothelial senescence through a SIRT1-dependent mechanism

Abstract

PURPOSE:Accumulation of senescent endothelial cells (ECs) and development of vascular aging have been implicated in the etiology of vascular dysfunction and disease. Aerobic exercise has been recognized as the single most effective non-pharmacological anti-aging intervention via increased laminar shear stress (LSS). This study aimed to determine the protective effects of LSS against premature senescence and the underlying mechanism. METHODS: Carotid artery partial ligation surgery was performed on the left carotid arteries (LCAs) of C57BL/6J male mice to determine the effect of disturbed flow on the development of endothelial senescence. Senescence-associated β-galactosidase (SA-β-gal) staining was performed to measure cellular senescence. Expression levels of protein markers for cell senescence including p21, p16, and p53 were measured by western blotting. RESULTS: En face SA-β-gal staining was identified only in the partially ligated LCAs of voluntary wheel-running mice, suggesting a direct relevance of LSS on the prevention of vascular senescence. In the in vitro H2O2-induced premature senescence model, preconditioning of high-flow LSS (20 dyne/cm2 , 36 hours) induced significant reduction in the percentage of SA-β-gal positive ECs. Expression of the molecular markers of cellular senescence such as p21, p16, and p53 was significantly decreased by LSS pretreatment. However, the protective effects of LSS against premature senescence were completely abolished by SIRT1 inhibition. CONCLUSIONS: The results suggest that high-flow LSS has protective effects against oxidative stress-induced premature endothelial senescence through a SIRT1-dependent mechanism

참고문헌 (34)

  1. Erusalimsky JD, "Vascular endothelial senescence : from mechanisms to pathophysiology", J Appl Physiol(1985), 106(1), pp.326~332 (2009)
  2. Lakatta EG, "Arterial and cardiac aging : major shareholders in cardiovascular disease enterprises : Part III : cellular and molecular clues to heart and arterial aging", Circulation, 107(3), pp.490~497 (2003)
  3. Minamino T, "Endothelial cell senescence in human atherosclerosis : role of telomere in endothelial dysfunction", Circulation, 105(13), pp.1541~1544 (2002)
  4. Erusalimsky JD, "Cellular senescence in vivo : its relevance in ageing and cardiovascular disease", Exp Gerontol, 40(8-9), pp.634~642 (2005)
  5. Wang JC, "Aging and atherosclerosis : mechanisms, functional consequences, and potential therapeutics for cellular senescence", Circ Res, 111(2), pp.245~259 (2012)
  6. Marin C, "Endothelial aging associated with oxidative stress can be modulated by a healthy mediterranean diet", Int J Mol Sci, 14(5), pp.8869~8889 (2013)
  7. Liu H, "Redox-dependent transcriptional regulation", Circ Res, 97(10), pp.967~974 (2005)
  8. Okabe TA, "Swimming reduces the severity of atherosclerosis in apolipoprotein E deficient mice by antioxidant effects", Cardiovasc Res, 74(3), pp.537~545 (2007)
  9. Malek AM, "Hemodynamic shear stress and its role in atherosclerosis", JAMA, 282(21), pp.2035~2042 (1999)
  10. Taylor CA, "Effect of exercise on hemodynamic conditions in the abdominal aorta", J Vasc Surg, 29(6), pp.1077~1089 (1999)
  11. Cheng C, "Abdominal aortic hemodynamic conditions in healthy subjects aged 50–70 at rest and during lower limb exercise : in vivo quantification using MRI", Atherosclerosis, 168(2), pp.323~331 (2003)
  12. Kim JS, "Shear stress-in-duced mitochondrial biogenesis decreases the release of microparticles from endothelial cells", Am J Physiol Heart Circ Physiol, 309(3), pp.H425~H433 (2015)
  13. Ando J, "Shear stress inhibits adhesion of cultured mouse endothelial cells to lymphocytes by downregulating VCAM-1 expression", Am J Physiol, 267(3 Pt 1), pp.C679~C687 (1994)
  14. Dimmeler S, "Shear stress inhibits apoptosis of human endothelial cells", FEBS Lett, 399(1-2), pp.71~74 (1996)
  15. Haigis MC, "Mammalian sirtuins : biological insights and disease relevance", Annu Rev Pathol, 5, pp.253~295 (2010)
  16. Braunstein M, "Transcriptional silencing in yeast is associated with reduced nucleosome acetylation", Genes Dev, 7(4), pp.592~604 (1993)
  17. Borradaile NM, "NAD(+), sirtuins, and cardiovascular disease", Curr Pharm Des, 15(1), pp.110~117 (2009)
  18. Potente M, "SIRT1 controls endothelial angiogenic functions during vascular growth", Genes Dev, 21(20), pp.2644~2658 (2007)
  19. Ota H, "Induction of endothelial nitric oxide synthase, SIRT1, and catalase by statins inhibits endothelial senescence through the Akt pathway", Arterioscler Thromb Vasc Biol, 30(11), pp.2205~2211 (2010)
  20. Chen Z, "Shear stress, SIRT1, and vascular homeostasis", Proc Natl Acad Sci U S A, 107(22), pp.10268~10273 (2010)
  21. Kim B, "Exercise-mediated wall shear stress increases mitochondrial biogenesis in vascular endothelium", PLoS One, 9(11), pp.e111409~ (2014)
  22. Nam D, "Partial carotid ligation is a model of acutely induced disturbed flow, leading to rapid endothelial dysfunction and atherosclerosis", Am J Physiol Heart Circ Physiol, 297(4), pp.H1535~H1543 (2009)
  23. Nam D, "A model of disturbed flow-induced atherosclerosis in mouse carotid artery by partial ligation and a simple method of RNA isolation from carotid endothelium", J Vis Exp (2010)[DOI]
  24. Park JY, "NFKB1promoter variation implicates shear-induced NOS3 gene expression and endothelial function in prehypertensives and stage I hypertensives", Am J Physiol Heart Circ Physiol, 293(4), pp.H2320~H2327 (2007)
  25. Dimri GP, "A biomarker that identifies senescent human cells in culture and in aging skin in vivo", Proc Natl Acad Sci U S A, 92(20), pp.9363~9367 (1995)
  26. Brown MD, "Racial differences in tumor necrosis factor-alpha-induced endothelial microparticles and interleukin-6 production", Vasc Health Risk Manag, 7, pp.541~550 (2011)
  27. Warboys CM, "Disturbed Flow Promotes Endothelial Senescence via a p53-Dependent Pathway", Arterioscler Thromb Vasc Biol (2014)[DOI]
  28. Ota H, "Sirt1 modulates premature senescence-like phenotype in human endothelial cells", J Mol Cell Cardiol, 43(5), pp.571~579 (2007)
  29. Kao CL, "Resveratrol protects human endothelium from H2O2-induced oxidative stress and senescence via SirT1 activation", J Atheroscler Thromb, 17(9), pp.970~979 (2010)
  30. Botden IP, "Red wine extract protects against oxidative-stress-induced endothelial senescence", Clin Sci(Lond), 123(8), pp.499~507 (2012)
  31. Feletou M, "Endothelial dysfunction : a multifaceted disorder(The Wiggers Award Lecture)", Am J Physiol Heart Circ Physiol, 291(3), pp.H985~H1002 (2006)
  32. Lin JR, "Downregulation of dynamin-related protein 1 contributes to impaired autophagic flux and angiogenic function in senescent endothelial cells", Arterioscler Thromb Vasc Biol, 35(6), pp.1413~1422 (2015)
  33. Ungvari Z, "Resveratrol increases vascular oxidative stress resistance", Am J Physiol Heart Circ Physiol, 292(5), pp.H2417~H2424 (2007)
  34. Ungvari Z, "Resveratrol confers endothelial protection via activation of the antioxidant transcription factor Nrf2", Am J Physiol Heart Circ Physiol, 299(1), pp.H18~H24 (2010)

관련 논문AI추천

이 간행물의 다른 논문 (15건)