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STATE-OF-ART PAPER

The clinical implications of endothelial dysfunction

^* Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts, USA

Manuscript received February 18, 2003; revised manuscript received April 27, 2003, accepted June 5, 2003.

^* Reprint requests and correspondence: Dr. Joseph A. Vita, Section of Cardiology, Boston Medical Center, 88 East Newton Street, Boston, Massachusetts 02118, USA.
jvita{at}bu.edu

Defining new approaches for the prevention and treatment of atherosclerosis is an important priority. Recently, measurement of endothelial function in patients has emerged as a useful tool for atherosclerosis research. Risk factors are associated with impaired endothelial function, and clinical syndromes relate, in part, to a loss of endothelial control of vascular homeostasis. Recent studies have shown that the severity of endothelial dysfunction relates to cardiovascular risk. A growing number of interventions known to reduce cardiovascular risk have been shown to improve endothelial function. This work suggests that studies of endothelial function could be used in the care of patients and as a surrogate marker for the evaluation of new therapeutic strategies. This article will review this growing literature in an effort to evaluate the current clinical utility of endothelial dysfunction.

Abbreviations and Acronyms   BP = blood pressure   CAD = coronary artery disease   CVD = cardiovascular disease   FMD = flow-mediated dilation   HRT = hormone replacement therapy   ICAM = intercellular adhesion molecule   NO = nitric oxide   VCAM-1 = vascular cell adhesion molecule-1

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				C. Cheng, C. Daskalakis, and B. Falkner Original Research: Capillary rarefaction in treated and untreated hypertensive subjects Therapeutic Advances in Cardiovascular Disease, April 1, 2008; 2(2): 79 - 88. [Abstract] [PDF]

				R. Rossi, A. Nuzzo, G. Origliani, and M. G. Modena Prognostic Role of Flow-Mediated Dilation and Cardiac Risk Factors in Post-Menopausal Women J. Am. Coll. Cardiol., March 11, 2008; 51(10): 997 - 1002. [Abstract] [Full Text] [PDF]

				E. V. Brauner, L. Forchhammer, P. Moller, L. Barregard, L. Gunnarsen, A. Afshari, P. Wahlin, M. Glasius, L. O. Dragsted, S. Basu, et al. Indoor Particles Affect Vascular Function in the Aged: An Air Filtration-based Intervention Study Am. J. Respir. Crit. Care Med., February 15, 2008; 177(4): 419 - 425. [Abstract] [Full Text] [PDF]

				M. Kooijman, D. H. J. Thijssen, P. C. E. de Groot, M. W. P. Bleeker, H. J. M. van Kuppevelt, D. J. Green, G. A. Rongen, P. Smits, and M. T. E. Hopman Flow-mediated dilatation in the superficial femoral artery is nitric oxide mediated in humans J. Physiol., February 15, 2008; 586(4): 1137 - 1145. [Abstract] [Full Text] [PDF]

				C. Heiss, R. E. Sievers, N. Amabile, T. Y. Momma, Q. Chen, S. Natarajan, Y. Yeghiazarians, and M. L. Springer In vivo measurement of flow-mediated vasodilation in living rats using high-resolution ultrasound Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H1086 - H1093. [Abstract] [Full Text] [PDF]

				T. B. Vaughan, F. Ovalle, and E. Moreland Vascular disease in paediatric type 2 diabetes: the state of the art Diabetes and Vascular Disease Research, December 1, 2007; 4(4): 297 - 304. [Abstract] [PDF]

				N. M. Hamburg, C. J. McMackin, A. L. Huang, S. M. Shenouda, M. E. Widlansky, E. Schulz, N. Gokce, N. B. Ruderman, J. F. Keaney Jr, and J. A. Vita Physical Inactivity Rapidly Induces Insulin Resistance and Microvascular Dysfunction in Healthy Volunteers Arterioscler Thromb Vasc Biol, December 1, 2007; 27(12): 2650 - 2656. [Abstract] [Full Text] [PDF]

				L. G. Spagnoli, E. Bonanno, G. Sangiorgi, and A. Mauriello Role of Inflammation in Atherosclerosis J. Nucl. Med., November 1, 2007; 48(11): 1800 - 1815. [Abstract] [Full Text] [PDF]

				S. M. Shenouda and J. A. Vita Effects of Flavonoid-Containing Beverages and EGCG on Endothelial Function J. Am. Coll. Nutr., August 1, 2007; 26(4): 366S - 372S. [Abstract] [Full Text] [PDF]

				G. Peluffo and R. Radi Biochemistry of protein tyrosine nitration in cardiovascular pathology Cardiovasc Res, July 15, 2007; 75(2): 291 - 302. [Abstract] [Full Text] [PDF]

				A. J. Donato, I. Eskurza, A. E. Silver, A. S. Levy, G. L. Pierce, P. E. Gates, and D. R. Seals Direct Evidence of Endothelial Oxidative Stress With Aging in Humans: Relation to Impaired Endothelium-Dependent Dilation and Upregulation of Nuclear Factor-{kappa}B Circ. Res., June 8, 2007; 100(11): 1659 - 1666. [Abstract] [Full Text] [PDF]

				S. J Hamilton, G. T Chew, and G. F Watts Therapeutic regulation of endothelial dysfunction in type 2 diabetes mellitus Diabetes and Vascular Disease Research, June 1, 2007; 4(2): 89 - 102. [Abstract] [PDF]

				S. C. Lim, N. G. Morgenthaler, T. Subramaniam, Y. S. Wu, S. K. Goh, and C. F. Sum The Relationship Between Adrenomedullin, Metabolic Factors, and Vascular Function in Individuals With Type 2 Diabetes Diabetes Care, June 1, 2007; 30(6): 1513 - 1519. [Abstract] [Full Text] [PDF]

				J. Yeboah, J. R. Crouse, F.-C. Hsu, G. L. Burke, and D. M. Herrington Brachial Flow-Mediated Dilation Predicts Incident Cardiovascular Events in Older Adults: The Cardiovascular Health Study Circulation, May 8, 2007; 115(18): 2390 - 2397. [Abstract] [Full Text] [PDF]

				E. Esteve, A. Castro, A. Lopez-Bermejo, J. Vendrell, W. Ricart, and J.-M. Fernandez-Real Serum Interleukin-6 Correlates With Endothelial Dysfunction in Healthy Men Independently of Insulin Sensitivity Diabetes Care, April 1, 2007; 30(4): 939 - 945. [Abstract] [Full Text] [PDF]

				M. E. Widlansky, N. M. Hamburg, E. Anter, M. Holbrook, D. F. Kahn, J. G. Elliott, J. F. Keaney Jr., and J. A. Vita Acute EGCG Supplementation Reverses Endothelial Dysfunction in Patients with Coronary Artery Disease J. Am. Coll. Nutr., April 1, 2007; 26(2): 95 - 102. [Abstract] [Full Text] [PDF]

				A. Barac, U. Campia, and J. A. Panza Methods for Evaluating Endothelial Function in Humans Hypertension, April 1, 2007; 49(4): 748 - 760. [Full Text] [PDF]