Association between coronary endothelial dysfunction and local inflammation of atherosclerotic coronary arteries

We have examined a possibility whether or not severity and extent of coronary atherosclerosis may associate with degree of local inflammation in relation to endothelial dysfunction as is indicated by reduced NO formation. Blood samples were obtained from aortic root (Ao) and coronary sinus (CS) of 39 patients who underwent coronary angiography. Plasma NOx levels (nitrite + nitrate, stable NO end-products) were evaluated by HPLC-Griess system, and markers of inflammation, C-reactive protein (CRP) and serum amyloid A protein (SAA), were measured by Latex Turbidimetric Immunoassay. To evaluate the changes of these substances through coronary circulation, the percentage changes of respective markers [(CS — Ao) x 100/Ao] were calculated. The extent and severity of atherosclerosis of left coronary arteries were evaluated with Gensini Score (GS). The GS correlated with the percentage changes of NOx (r = -0.35, p < 0.05) and that of SAA (r = 0.43, p < 0.05) across coronary circulation, but not with changes in CRP. Moreover, the percentage changes of NOx correlated with that of SAA (r = -0.36, p < 0.05). These results indicated that severity and extent of coronary atherosclerosis related to degree of local inflammation which has a possible association with coronary endothelial dysfunction. (Mol Cell Biochem 249: 67–73, 2003)

[1]  J. Beckman.  Oxidative damage and tyrosine nitration from peroxynitrite. , 1996, Chemical research in toxicology.

[2]  P. Mcgeer,et al.  Generation of C-reactive protein and complement components in atherosclerotic plaques. , 2001, The American journal of pathology.

[3]  Y. Aizawa,et al.  Negative NO3- difference in human coronary circulation with severe atherosclerotic stenosis. , 1999, Life sciences.

[4]  Y. Aizawa,et al.  Decrease In Plasma NOx Concentration by Isosorbide Dinitrate, an Organic Nitrate Ester , 2003, Journal of cardiovascular pharmacology.

[5]  Y. Aizawa,et al.  Decrease of nitric oxide end-products during coronary circulation reflects elevated basal coronary artery tone in patients with vasospastic angina. , 2000, Japanese heart journal.

[6]  P. Ridker,et al.  Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. , 1997, The New England journal of medicine.

[7]  D. Tate,et al.  Sites of interleukin-6 release in patients with acute coronary syndromes and in patients with congestive heart failure. , 2000, The American journal of cardiology.

[8]  E. Antman,et al.  Serum amyloid A predicts early mortality in acute coronary syndromes: A TIMI 11A substudy. , 2000, Journal of the American College of Cardiology.

[9]  W. Koenig,et al.  C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[10]  Y. Aizawa,et al.  Respiratory alkalosis does not alter NOx concentrations in human plasma and erythrocytes. , 2001, American journal of physiology. Heart and circulatory physiology.

[11]  P. Ridker,et al.  C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. , 2000, The New England journal of medicine.

[12]  G. Gensini,et al.  A more meaningful scoring system for determining the severity of coronary heart disease. , 1983, The American journal of cardiology.

[13]  U. Ikeda,et al.  Interleukin 6 expression in coronary circulation after coronary angioplasty as a risk factor for restenosis , 2000, Heart.

[14]  M. Hori,et al.  Reduced plasma concentrations of nitrogen oxide in individuals with essential hypertension. , 1997, Hypertension.

[15]  S. Urieli-Shoval,et al.  Expression of apolipoprotein serum amyloid A mRNA in human atherosclerotic lesions and cultured vascular cells: implications for serum amyloid A function. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[16]  M. Kuzuya,et al.  Expression of inducible nitric oxide synthase in T lymphocytes and macrophages of cholesterol-fed rabbits. , 1997, Atherosclerosis.

[17]  A. Rebuzzi,et al.  The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. , 1994, The New England journal of medicine.

[18]  A. Quyyumi,et al.  Nitric oxide activity in the atherosclerotic human coronary circulation. , 1997, Journal of the American College of Cardiology.

[19]  S. Lestavel,et al.  Role of serum amyloid A during metabolism of acute-phase HDL by macrophages. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[20]  S. Higano,et al.  Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. , 2000, Circulation.

[21]  D. Rothenbacher,et al.  Role of novel markers of inflammation in patients with stable coronary heart disease. , 2001, The American journal of cardiology.

[22]  J. Keaney,et al.  Atherosclerosis, oxidative stress, and antioxidant protection in endothelium-derived relaxing factor action. , 1995, Progress in cardiovascular diseases.

[23]  J. Umans,et al.  Nitric oxide in the regulation of blood flow and arterial pressure. , 1995, Annual review of physiology.

[24]  A M Zeiher,et al.  Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. , 2000, Circulation.

[25]  A. Rebuzzi,et al.  Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability. , 1999, Circulation.

[26]  N. Rifai,et al.  Inflammatory markers in men with angiographically documented coronary heart disease. , 1999, Clinical chemistry.

[27]  S. Nakano,et al.  PARADOXICAL DECREASE IN PLASMA NOx BY L-ARGININE LOAD IN DIABETIC AND NON-DIABETIC SUBJECTS , 2002, Clinical and experimental hypertension.