The complex link between oxidised low-density lipoprotein and unstable angina

Objective The role of oxidised low-density lipoprotein (ox-LDL) in plaque destabilisation is controversial; therefore we aimed at comparing plaque and plasma ox-LDL content in stable and unstable ischaemic syndromes. We also assessed the correlation between plaque or plasma ox-LDL and angiographic complex stenosis morphology. Methods Ten consecutive patients with chronic stable angina (SA) and 10 consecutive patients with unstable angina (UA) were studied. Plaque sections obtained by directional coronary atherectomy were immunostained with the monoclonal antibody mAb-4E6, which recognises several oxidation epitopes on LDL (mAb-4E6 ox-LDL), and with the monoclonal antibody mAb-1H11 (mAb-1H11 ox-LDL), which recognises malondialdehyde-modified LDL. An mAb-4E6-based competition ELISA was used for quantification of ox-LDL in plasma. C-reactive protein serum levels were measured by a high-sensitivity nephelometric assay. An angiographic analysis was performed to assess severity and extent of coronary atherosclerotic disease and stenosis morphology. Results Percent plaque area occupied by mAb-4E6 ox-LDL or mAb-1H11 ox-LDL was similar in patients with SA or UA (22.4 ± 13.1 vs. 21.1 ± 19.7%, P = 0.8 and 19.3 ± 10.4 vs. 16.8 ± 16.9%, P = 0.6, respectively), whereas ox-LDL plasma levels were significantly higher in patients with UA than in patients with SA (2.4 ± 1.1 vs. 0.9 ± 0.6 mg/dl; P = 0.03). Furthermore, a significant correlation was found between plasma levels of ox-LDL and the number of angiographically complex lesions (P = 0.03) or C-reactive protein serum levels (P = 0.04). Conclusions Neither plaque mAb-4E6 ox-LDL nor plaque mAb-1H11 ox-LDL seem to be a major trigger of coronary plaque instability. However, circulating ox-LDL might be involved in plaque vulnerability and coronary artery disease activity.

[1]  C. Vassanelli,et al.  Plasma levels of oxidized-low-density lipoproteins are higher in patients with unstable angina and correlated with angiographic coronary complex plaques. , 2006, Atherosclerosis.

[2]  Alexander Reinecke,et al.  Detection of Diverse Bacterial Signatures in Atherosclerotic Lesions of Patients With Coronary Heart Disease , 2006, Circulation.

[3]  J. Tijssen,et al.  Colocalisation of intraplaque C reactive protein, complement, oxidised low density lipoprotein, and macrophages in stable and unstable angina and acute myocardial infarction , 2006, Journal of Clinical Pathology.

[4]  T. Sawamura,et al.  Enhanced plasma levels of oxidized low-density lipoprotein increase circulating nuclear factor-kappa B activation in patients with unstable angina. , 2005, Journal of the American College of Cardiology.

[5]  E. Brilakis,et al.  Oxidized phospholipids, Lp(a) lipoprotein, and coronary artery disease. , 2005, The New England journal of medicine.

[6]  J. Kaski,et al.  C-reactive protein elevation and disease activity in patients with coronary artery disease. , 2004, European heart journal.

[7]  H. Horiguchi,et al.  Oxidized LDL in Carotid Plaques and Plasma Associates With Plaque Instability , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[8]  G Finet,et al.  Multiple Atherosclerotic Plaque Rupture in Acute Coronary Syndrome: A Three-Vessel Intravascular Ultrasound Study , 2002, Circulation.

[9]  P. Holvoet,et al.  Oxidized LDL and HDL: antagonists in atherothrombosis , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[10]  D. Stengel,et al.  Prevents Injury-induced Neointima Formation and Reduces Spontaneous Atherosclerosis in Acetylhydrolase − Adenovirus-mediated Gene Transfer of Human Platelet-activating Factor Adenovirus-mediated Gene Transfer of Human Platelet-activating Factor–acetylhydrolase Prevents Injury-induced Neointima Forma , 2022 .

[11]  T. Matsuo,et al.  Elevated Levels of Oxidized Low Density Lipoprotein Show a Positive Relationship With the Severity of Acute Coronary Syndromes , 2001, Circulation.

[12]  M. Hori,et al.  Extensive development of vulnerable plaques as a pan-coronary process in patients with myocardial infarction: an angioscopic study. , 2001, Journal of the American College of Cardiology.

[13]  F. Crea,et al.  Large, sustained cardiac lipid peroxidation and reduced antioxidant capacity in the coronary circulation after brief episodes of myocardial ischemia. , 2000, Journal of the American College of Cardiology.

[14]  K. Williams,et al.  Atherosclerosis--an inflammatory disease. , 1999, The New England journal of medicine.

[15]  F. Werf,et al.  Oxidized LDL and malondialdehyde-modified LDL in patients with acute coronary syndromes and stable coronary artery disease. , 1998, Circulation.

[16]  D. Jones,et al.  Oxidatively modified LDL contains phospholipids with platelet-activating factor-like activity and stimulates the growth of smooth muscle cells. , 1995, The Journal of clinical investigation.

[17]  J. Kaski,et al.  Rapid angiographic progression of coronary artery disease in patients with angina pectoris. The role of complex stenosis morphology. , 1995, Circulation.

[18]  P. Libby.  Molecular bases of the acute coronary syndromes. , 1995, Circulation.

[19]  T. Marwick,et al.  A new method of scoring coronary angiograms to reflect extent of coronary atherosclerosis and improve correlation with major risk factors. , 1990, American heart journal.

[20]  Gerrity Rg.  The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions. , 1981 .

[21]  R. Gerrity.  The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions. , 1981, The American journal of pathology.