In vivo low density lipoprotein oxidation relates to coronary reactivity in young men

Department of Clinical Physiology, University of Turku, Finland. olli.raitakari@utu.fi

OBJECTIVES: This study was undertaken to examine the relation of in vivo low density lipoprotein (LDL) oxidation and other lipid risk factors to coronary reactivity in normal subjects. BACKGROUND: Experimental studies have shown that oxidized LDL (ox-LDL) particles are injurious to the vascular wall by impairing its normal vasodilator function. METHODS: We used noninvasive positron emission tomographic (PET) imaging with intravenous dipyridamole to measure coronary flow reserve, a marker of coronary endothelial and smooth muscle function, in 30 healthy men (mean [+/-SD] age 34.4 +/- 3.2 years). As a marker of in vivo LDL oxidation, the autoantibody titer against ox-LDL was measured by the enzyme-linked immunosorbent assay method. RESULTS: Plasma levels of autoantibody titer against ox-LDL were inversely associated with coronary flow reserve (r = -0.42, p = 0.023). High LDL cholesterol levels (above median > 3.0 mmol/liter) were associated with a low coronary flow reserve only in subjects expressing simultaneously high levels of ox-LDL titer (above median). Subjects with simultaneously high levels of LDL cholesterol and ox-LDL titer had lower coronary flow reserve values than subjects in other groups (3.89 vs. > 5.0 in other groups, p = 0.066). CONCLUSIONS: These data provide evidence for the role of ox-LDL in affecting the coronary reactivity in vivo and support the concept that oxidative modification of LDL particles provides a mechanism by which high LDL concentrations exhibit injurious effects on the coronary vascular bed.

This article has been cited by other articles:

				M. J. Haller, M. Samyn, W. W. Nichols, T. Brusko, C. Wasserfall, R. F. Schwartz, M. Atkinson, J. J. Shuster, G. L. Pierce, and J. H. Silverstein Radial Artery Tonometry Demonstrates Arterial Stiffness in Children With Type 1 Diabetes Diabetes Care, December 1, 2004; 27(12): 2911 - 2917. [Abstract] [Full Text] [PDF]

				Y. Shoenfeld, R. Wu, L. D. Dearing, and E. Matsuura Are Anti-Oxidized Low-Density Lipoprotein Antibodies Pathogenic or Protective? Circulation, October 26, 2004; 110(17): 2552 - 2558. [Full Text] [PDF]

				T. Janatuinen, J. Knuuti, J. O. Toikka, M. Ahotupa, P. Nuutila, T. Ronnemaa, and O. T. Raitakari Effect of Pravastatin on Low-Density Lipoprotein Oxidation and Myocardial Perfusion in Young Adults With Type 1 Diabetes Arterioscler Thromb Vasc Biol, July 1, 2004; 24(7): 1303 - 1308. [Abstract] [Full Text] [PDF]

				M. J. Jarvisalo, M. Raitakari, J. O. Toikka, A. Putto-Laurila, R. Rontu, S. Laine, T. Lehtimaki, T. Ronnemaa, J. Viikari, and O. T. Raitakari Endothelial Dysfunction and Increased Arterial Intima-Media Thickness in Children With Type 1 Diabetes Circulation, April 13, 2004; 109(14): 1750 - 1755. [Abstract] [Full Text] [PDF]

				T. O. Kiviniemi, M. Saraste, J. W. Koskenvuo, K. E. J. Airaksinen, J. O. Toikka, A. Saraste, J. P. Parkka, and J. J. Hartiala Coronary artery diameter can be assessed reliably with transthoracic echocardiography Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1515 - H1520. [Abstract] [Full Text] [PDF]

				M. Raitakari, T. Ilvonen, M. Ahotupa, T. Lehtimaki, A. Harmoinen, P. Suominen, J. Elo, J. Hartiala, and O. T. Raitakari Weight Reduction With Very-Low-Caloric Diet and Endothelial Function in Overweight Adults: Role of Plasma Glucose Arterioscler Thromb Vasc Biol, January 1, 2004; 24(1): 124 - 128. [Abstract] [Full Text] [PDF]

				H. Jokela, P. Dastidar, R. Rontu, A. Salomaki, K. Teisala, T. Lehtimaki, and R. Punnonen Effects of Long-Term Estrogen Replacement Therapy Versus Combined Hormone Replacement Therapy on Nitric Oxide-Dependent Vasomotor Function J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4348 - 4354. [Abstract] [Full Text] [PDF]

				H. Paiva, J. Laakso, H. Laine, R. Laaksonen, J. Knuuti, and O. T. Raitakari Plasma asymmetric dimethylarginine and hyperemic myocardial blood flow in young subjects with borderline hypertension or familial hypercholesterolemia J. Am. Coll. Cardiol., October 2, 2002; 40(7): 1241 - 1247. [Abstract] [Full Text] [PDF]

				J. T. Cvetkovic, S. Wallberg-Jonsson, E. Ahmed, S. Rantapaa-Dahlqvist, and A. K. Lefvert Increased levels of autoantibodies against copper-oxidized low density lipoprotein, malondialdehyde-modified low density lipoprotein and cardiolipin in patients with rheumatoid arthritis Rheumatology, September 1, 2002; 41(9): 988 - 995. [Abstract] [Full Text] [PDF]

				G. Theilmeier, P. Verhamme, S. Dymarkowski, H. Beck, H. Bernar, M. Lox, S. Janssens, M.-C. Herregods, E. Verbeken, D. Collen, et al. Hypercholesterolemia in Minipigs Impairs Left Ventricular Response to Stress: Association With Decreased Coronary Flow Reserve and Reduced Capillary Density Circulation, August 27, 2002; 106(9): 1140 - 1146. [Abstract] [Full Text] [PDF]

				M Fujiwara, T Tamura, K Yoshida, K Nakagawa, M Nakao, M Yamanouchi, N Shikama, T Himi, and Y Masuda Coronary flow reserve in angiographically normal coronary arteries with one-vessel coronary artery disease without traditional risk factors Eur. Heart J., March 2, 2001; 22(6): 479 - 487. [Abstract] [PDF]

				W. F. Penny, O. Ben-Yehuda, K. Kuroe, J. Long, A. Bond, V. Bhargava, J. F. Peterson, M. McDaniel, J. Juliano, J. L. Witztum, et al. Improvement of coronary artery endothelial dysfunction with lipid-lowering therapy: heterogeneity of segmental response and correlation with plasma-oxidized low density lipoprotein J. Am. Coll. Cardiol., March 1, 2001; 37(3): 766 - 774. [Abstract] [Full Text] [PDF]

				O. T. Raitakari, M. R. Adams, R. J. McCredie, K. A. Griffiths, R. Stocker, and D. S. Celermajer Oral vitamin C and endothelial function in smokers: short-term improvement, but no sustained beneficial effect J. Am. Coll. Cardiol., May 1, 2000; 35(6): 1616 - 1621. [Abstract] [Full Text] [PDF]

				A. T. Erkkila, O. Narvanen, S. Lehto, M. I. J. Uusitupa, and S. Yla-Herttuala Autoantibodies Against Oxidized Low-Density Lipoprotein and Cardiolipin in Patients With Coronary Heart Disease Arterioscler Thromb Vasc Biol, January 1, 2000; 20(1): 204 - 209. [Abstract] [Full Text] [PDF]

				E. Ahmed, J. Trifunovic, B. Stegmayr, G. Hallmans, and A. K. Lefvert Autoantibodies Against Oxidatively Modified LDL Do Not Constitute a Risk Factor for Stroke : A Nested Case-Control Study Stroke, December 1, 1999; 30(12): 2541 - 2546. [Abstract] [Full Text] [PDF]

				I. Yokoyama, S.-i. Momomura, T. Ohtake, K. Yonekura, W. Yang, N. Kobayakawa, T. Aoyagi, S. Sugiura, N. Yamada, K. Ohtomo, et al. Improvement of Impaired Myocardial Vasodilatation Due to Diffuse Coronary Atherosclerosis in Hypercholesterolemics After Lipid-Lowering Therapy Circulation, July 13, 1999; 100(2): 117 - 122. [Abstract] [Full Text] [PDF]

				O.-P. Pitkanen, P. Nuutila, O. T. Raitakari, K. Porkka, H. Iida, I. Nuotio, T. Ronnemaa, J. Viikari, M.-R. Taskinen, C. Ehnholm, et al. Coronary Flow Reserve in Young Men With Familial Combined Hyperlipidemia Circulation, April 6, 1999; 99(13): 1678 - 1684. [Abstract] [Full Text] [PDF]

				O. T. Raitakari, M. R. Adams, and D. S. Celermajer Effect of Lp(a) on the Early Functional and Structural Changes of Atherosclerosis Arterioscler Thromb Vasc Biol, April 1, 1999; 19(4): 990 - 995. [Abstract] [Full Text] [PDF]

				J. O. Toikka, P. Niemi, M. Ahotupa, H. Niinikoski, J. S. A. Viikari, T. Ronnemaa, J. J. Hartiala, and O. T. Raitakari Large-Artery Elastic Properties in Young Men : Relationships to Serum Lipoproteins and Oxidized Low-Density Lipoproteins Arterioscler Thromb Vasc Biol, February 1, 1999; 19(2): 436 - 441. [Abstract] [Full Text] [PDF]

				T. Lehtimaki, S. Lehtinen, T. Solakivi, M. Nikkila, O. Jaakkola, H. Jokela, S. Yla-Herttuala, J. S. Luoma, T. Koivula, and T. Nikkari Autoantibodies Against Oxidized Low Density Lipoprotein in Patients With Angiographically Verified Coronary Artery Disease Arterioscler Thromb Vasc Biol, January 1, 1999; 19(1): 23 - 27. [Abstract] [Full Text] [PDF]