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Endothelin-1 system activity in adults with borderline high ldl-cholesterol

Artery Research volume 8, pages 115–118 (2014)Cite this article

Abstract

Background

Modest elevations in plasma low-density lipoprotein (LDL)-cholesterol have been shown to confer a significant increase in cardiovascular risk. Endothelin (ET)-1 is a vasoconstrictor peptide with proatherogenic properties. The experimental aim of this study was to determine whether ET-1 system activity is elevated in adults with borderline high LDL-cholesterol, independent of other cardiometabolic abnormalities.

Methods

Forearm blood flow (FBF; plethysmography) responses to intra-arterial infusion of ET-1, selective ETA receptor blockade (BQ-123), and non-selective ETA/B blockade (BQ-123 + BQ-788) were determined in 40 middle-aged and older adults (45–70 years): 20 with optimal/near optimal LDL-cholesterol (<3.4 mmol/L) and 20 with borderline-high LDL-cholesterol (3.4–4.1 mmol/L).

Results

Both groups demonstrated a similar, non-significant (~10%) reduction in FBF to ET-1. BQ-123 and BQ-123 + 788 elicited a modest, but significant, increase in FBF (~15–20%) in each group. However, there were no group differences in the FBF responses to either selective ETA or non-selective ETA/B receptor antagonism.

Conclusion

Borderline-high LDL-C is not associated with increased ET-1 mediated vasoconstrictor tone. Disrupted ET-1 system activity may not contribute to the increased cardiovascular risk burden with borderline-high LDL-cholesterol.

References

  1. Grundy SM, Cleeman JI, Merz CN, Brewer Jr HB, Clark LT, Hunninghake DB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. J Am Coll Cardiol 2004;44:720–32.

    Google Scholar 

  2. Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837–47.

    Google Scholar 

  3. Cremer P, Nagel D, Labrot B, Mann H, Muche R, Elster H, et al. Lipoprotein Lp(a) as predictor of myocardial infarction in comparison to fibrinogen, LDL cholesterol and other risk factors: results from the prospective Gottingen Risk Incidence and Prevalence Study (GRIPS). Eur J Clin Invest 1994;24:444–53.

    Google Scholar 

  4. Miyauchi T, Masaki T. Pathophysiology of endothelin in the cardiovascular system. Annu Rev Physiol 1999;61:391–415.

    Google Scholar 

  5. Luscher T, Barton M. Endothelins and endothelin receptor antagonists: therapeutic considerations for a novel class of cardiovascular drugs. Circulation 2000;102:2434–40.

    Google Scholar 

  6. Ihling C, Szombathy T, Bohrmann B, Brockhaus M, Schaefer HE, Loeffler BM. Coexpression of endothelin-converting enzyme-1 and endothelin-1 in different stages of human atherosclerosis. Circulation 2001;104:864–9.

    Google Scholar 

  7. Ravalli S, Szabolcs M, Albala A, Michler RE, Cannon PJ. Increased immunoreactive endothelin-1 in human transplant coronary artery disease. Circulation 1996;94:2096–102.

    Google Scholar 

  8. Guarda E, Katwa L, Myers P, Tyagi S, Weber K. Effects of endothelins on coloogen turnover in cardiac fibroblasts. Cardiovasc Res 1993;27:2130–4.

    Google Scholar 

  9. Lavallee M, Takamura M, Parent P, Thorin E. Crosstalk between endothelin and nitric oxide in the control of vascular tone. Heart Fail Rev 2001;6:265–76.

    Google Scholar 

  10. Dashwood M, Tsui J. Endothelin-1 and atherosclerossis: potential complications associated with endothelin-receptor blockade. Atherosclerosis 2002;160:297–304.

    Google Scholar 

  11. Kelly J, Whitworth J. Endothelin-1 as a mediator in cardiovascular disease. Clin Exp Pharmacol Physiol 1999;26:158–61.

    Google Scholar 

  12. Weil BR, Westby CM, Greiner JJ, Stauffer BL, DeSouza CA. Elevated endothelin-1 vasoconstrictor tone in prehypertensive adults. Can J Cardiol 2012;28:347–53.

    Google Scholar 

  13. Cardillo C, Kilcoyne C, Cannon R, Panza J. Increased activity of endougenous endothelin in patients with hypercholesterolemia. J Am Coll Cardiol 2000;36:1483–8.

    Google Scholar 

  14. Third Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel iii) final report. Circulation 2002;106:3143–421.

  15. Weil BR, Westby CM, Van Guilder GP, Greiner JJ, Stauffer BL, DeSouza CA. Enhanced endothelin-1 system activity with overweight and obesity. Am J Physiol Heart Circ Physiol 2011; 301:H689–95.

    Google Scholar 

  16. Diehl KJ, Templeton DL, Ma J, Weil BR, Greiner JJ, Stauffer BL, et al. Impaired fasting blood glucose is associated with increased endothelin-1 vasoconstrictor tone. Atherosclerosis 2013;229:130–3.

    Google Scholar 

  17. Cardillo C, Kilcoyne C, Waclawiw M, Cannon R, Panza J. Role of endothelin in the increased vascular tone of patients with essential hypertension. Hypertension 1999;33:753–8.

    Google Scholar 

  18. Cardillo C, Campia U, Bryant MB, Panza JA. Increased activity of endogenous endothelin in patients with type II diabetes mellitus. Circulation 2002;106:1783–7.

    Google Scholar 

  19. Diehl KJ, Stauffer BL, Greiner JJ, Weil BR, DeSouza CA. Nitric oxide-mediated endothlium-dependent vasodilation is impaired with borderline high-LDL cholesterol. Clin Transl Sci 2012;5:21–6.

    Google Scholar 

  20. Iglarz M, Clozel M. Mechanisms of ET-1-induced endothelial dysfunction. J Cardiovasc Pharmacol 2007;50:621–8.

    Google Scholar 

  21. Wagner OF, Christ G, Wojta J, Vierhapper H, Parzer S, Nowotny PJ, et al. Polar secretion of endothelin-1 by cultured endothelial cells. J Biol Chem 1992;267:16066–8.

    Google Scholar 

  22. Schiffrin EL. Vascular endothelin in hypertension. Vasc Pharmacol 2005;43:19–29. doi:S1537–1891.

  23. Walker AE, Eskurza I, Pierce GL, Gates PE, Seals DR. Modulation of vascular endothelial function by low-density lipoprotein cholesterol with aging: influence of habitual exercise. 2009;22:250–6.

    Google Scholar 

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Authors and Affiliations

  1. Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, 354 UCB, 80309, Boulder, CO, USA

    Kyle J. Diehl, Brian L. Stauffer, Jared J. Greiner & Christopher A. DeSouza

  2. Department of Medicine, University of Colorado Denver and the Health Sciences Center, 80045, Aurora, CO, USA

    Brian L. Stauffer & Christopher A. DeSouza

  3. Denver Health Medical Center, 80204, Denver, CO, USA

    Brian L. Stauffer

Authors
  1. Kyle J. Diehl
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  2. Brian L. Stauffer
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  3. Jared J. Greiner
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  4. Christopher A. DeSouza
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Correspondence to Christopher A. DeSouza.

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Diehl, K.J., Stauffer, B.L., Greiner, J.J. et al. Endothelin-1 system activity in adults with borderline high ldl-cholesterol. Artery Res 8, 115–118 (2014). https://doi.org/10.1016/j.artres.2014.03.002

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Keywords

Artery Research

ISSN: 1876-4401

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