This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Stanley, A. G Articles by Williams, B. Search for Related Content PubMed PubMed Citation Articles by Stanley, A. G Articles by Williams, B. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB LOSARTAN POTASSIUM Social Bookmarking                         What's this?

Mechanical strain-induced human vascular matrix synthesis: The role of angiotensin II

Cardiovascular Research Institute University of Leicester Leicester, UK, as90{at}le.ac.uk

Hash Patel

Cardiovascular Research Institute University of Leicester Leicester, UK

Abigail L Knight

Cardiovascular Research Institute University of Leicester Leicester, UK

Bryan Williams

Cardiovascular Research Institute University of Leicester Leicester, UK

Introduction: Reduced vascular compliance in patients with hypertension results from an increase in extra-cellular matrix (ECM) protein deposition in blood vessels. At least two key factors, namely mechanical strain and neurohumoral mediators, for example Angiotensin II (Ang II), promote fibrogenesis within vessel walls; however potential interactions between these have not been clearly defined. This work examined the direct effect of mechanical strain on matrix mRNA expression and protein synthesis by human vascular smooth muscle (VSM) cells and identified the importance of renin-angiotensin system (RAS) activation in stretch-induced matrix production.

Methods: Human VSM cells were exposed either to a cyclical mechanical strain regimen or to Ang II in the presence or absence of the Ang II receptor (AT₁ R) antagonist losartan or its more potent metabolite EXP3174. Analysis of matrix mRNA expression (Northerns) and protein synthesis (ELISA) and cellular AT₁-receptor protein expression (Westerns) were determined.

Results: Ang II increased both collagen 1 (92%, SEM +/-20%) mRNA expression and fibronectin (21% +/- 6%) protein synthesis in static VSM cells compared with unstimulated controls.The effect of Ang II was attenuated by antagonism of the AT ₁-receptor (AT₁ R). Similarly, mechanical strain induced an increase in both collagen 1 (102% +/- 30%) mRNA expression and fibronectin (50% +/-21%) protein synthesis. Surprisingly, in the absence of exogenous Ang II, AT₁-receptor blockade attenuated this stretch-induced increase in matrix synthesis. Mechanical strain also induced an increase in total cellular AT₁-receptor protein (30.7% +/- 3.5%) compared with static cells.

Conclusion: Both mechanical strain and Ang II increased matrix gene expression and protein synthesis by human VSM cells. The effect of strain was attenuated by AT ₁-receptor antagonism. Our results further suggest that mechanical strain may sensitise human VSM cells to the fibrogenic actions of Ang II, perhaps via upregulation of the AT₁-receptor.

Key Words: angiotensin II • mechanical strain • vascular smooth muscle cells • angiotensin receptors • vascular matrix

References

• Folkow B., Grimby G.,Thulesius O. Adaptive structural changes of the vascular wall in hypertension and their relationship to control of peripheral resistance. Acta Physiol Scand 1958; 44:255-72.[Web of Science][Medline] [Order article via Infotrieve]
• Folkow B. The structural factor in hypertension. In Hypertension: Pathophysiology, Diagnosis and Management. Edited by Laragh JH, Brenner BM. Raven Press Ltd. New York 1990; 565-81.
• Pang SC, Scott TM Stereological analysis of the tunica media of the aorta and renal artery during the development of hypertension in the spontaneously hypertensive rat. Journal of Anatomy 1981;133(Pt 4):513-26.[Web of Science][Medline] [Order article via Infotrieve]
• Roach MR, Burton AC The reason for the shape of the distensibility curves of arteries. Can J Biochem Physiol 1957;35:681-90.[Medline] [Order article via Infotrieve]
• O'Rouke M. Arterial function in health and disease. Edinburgh: Churchill-Livingstone 1982:170-82.
• Burke JM, Ross R. Synthesis of connective tissue macromolecules by smooth muscle. International Review of Connective Tissue Research 1979;8:119-57.[Medline] [Order article via Infotrieve]
• Mayne R. Vascular connective tissue: Normal biology and derangement in human diseases. In: Uitto J, Perejda Z, eds. Diseases of Connective Tissue: The Molecular Pathology of the Extracellular Matrix. New York: Marcel Dekker Inc.1984:271-308.
• Ford CM, Li S., Pickering JG Angiotensin II stimulates collagen synthesis in human vascular smooth muscle cells. Involvement of the AT 1-receptor, transforming growth factor b and tyrosine phosphorylation. ATV&B 1999; 19(8): 1843-53.3.
• O'Callaghan CO, Williams B. Mechanical strain increases matrix synthesis by human vascular smooth muscle cells: The role of TGFb. J Hypertension 1998; 16(suppl 2):S16.
• Stanley AG, Patel H., Williams B. Mechanical strain increases matrix synthesis in cultured Human Vascular Smooth Muscle Cells via an Angiotensin II-Dependent Pathway. Journal of Hypertension 1999; 17 (S3), S18.
• Stanley A., Patel H., Williams B. Evidence for the role of Angiotensin II and Mechanical Strain in vascular matrix production by human vascular smooth muscle cells. J Human Hypertens 1999;13:4.
• O'Callaghan CO,Williams B. Mechanical strain induced extracellular matrix production by human vascular smooth muscle cells: The role of TGFb1. Hypertension, in press.
• Sudhir K.,Wilson E., Chatterjee K., Ives HE Mechanical strain and collagen potentiate mitogenic activity of angiotensin II in rat vascular smooth muscle cells. J Clin Invest 1993; 92: 3003-07.[Web of Science][Medline] [Order article via Infotrieve]
• Sadoshima J-I.,Xu Y., Slayter HS, Izumo S.Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 1993; 75: 977-84[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Kojima M., Shiojima I.,Yamazaki T., Komuro I. et al. Angiotensin II receptor antagonist TCV-116 induces regression of hypertensive left ventricular in vivo and inhibits the intracellular signalling pathway of stretch-mediated cardiomyocyte hypertrophy in vitro. Circ 1994; 89:2204-211.1.[Abstract/Free Full Text]
• van Kesteren CAM, Saris JJ, Dekkers DHW et al. Cultured neonatal rat cardiac myocytes and fibroblasts do not synthesize renin or angiotensinogen: evidence for stretch-induced cardiomyocyte hypertrophy independent of angiotensin II. Circ Res 1999; 43:148-56.
• Kijima K., Matsibara H., Murasawa S. et al. Mechanical stretch induces enhanced expression of angiotensin II receptor subtypes in neonatal rat cardiac myocytes. Circ Res 1996; 79: 887-897.[Abstract/Free Full Text]
• Bardy N., Merval R., Benessiano J., Samuel J.-L,Tedgui A. Pressure and Angiotensin II synergistically induce aortic fibronectin expression in organ culture model of rat aorta. Circ Res 1996; 79:70-8.[Abstract/Free Full Text]
• Li Q., Muragaki Y., Ueno H., Ooshima A. Stretch-induced proliferation of cultured vascular smooth muscle cells and a possible involvement of local renin-angiotensin system and platelet derived growth factor. Hypertension Res 1997; 20: 217-23.[Medline] [Order article via Infotrieve]
• Yamazaki T., Komuro I., Kudoh, S. et al.Angiotensin II partly mediates mechanical stress-induced cardiac hypertrophy. Circ Res 1995; 77:258-65.[Abstract/Free Full Text]
• Williams B. Mechanical influences on vascular smooth muscle cell function. J Hypertens 1998;16:1921-9.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Williams B., Quinn-BakerA, Gallacher B., Lodwick D. Angiotensin II increases vascular permeability factor gene expression by human vascular smooth muscle cells. Hypertension 1995; 25:913-7.[Abstract/Free Full Text]
• Banes AJ, Link GW, Gilbert JW, Tay RTS, Monbureau O. Culturing cells in a mechanically active environment. Am Biotechnol Lab 1989; 8: 12-22.

Journal of Renin-Angiotensin-Aldosterone System, Vol. 1, No. 1, 32-35 (2000)
DOI: 10.3317/jraas.2000.007


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. A.A. Ewies, M. Elshafie, J. Li, A. Stanley, J. Thompson, J. Styles, I. White, and F. Al-Azzawi Changes in transcription profile and cytoskeleton morphology in pelvic ligament fibroblasts in response to stretch: the effects of estradiol and levormeloxifene Mol. Hum. Reprod., February 1, 2008; 14(2): 127 - 135. [Abstract] [Full Text] [PDF]

				S. Heeneman, J. C. Sluimer, and M. J.A.P. Daemen Angiotensin-Converting Enzyme and Vascular Remodeling Circ. Res., August 31, 2007; 101(5): 441 - 454. [Abstract] [Full Text] [PDF]

				A. M. Briones, M. Salaices, and E. Vila Mechanisms Underlying Hypertrophic Remodeling and Increased Stiffness of Mesenteric Resistance Arteries From Aged Rats J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2007; 62(7): 696 - 706. [Abstract] [Full Text] [PDF]

				B. C. Isenberg, C. Williams, and R. T. Tranquillo Small-Diameter Artificial Arteries Engineered In Vitro Circ. Res., January 6, 2006; 98(1): 25 - 35. [Abstract] [Full Text] [PDF]

This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Stanley, A. G Articles by Williams, B. Search for Related Content PubMed PubMed Citation Articles by Stanley, A. G Articles by Williams, B. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB LOSARTAN POTASSIUM Social Bookmarking                         What's this?