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CLINICAL RESEARCH: ACUTE CORONARY SYNDROME

Enhanced Plasma Levels of Oxidized Low-Density Lipoprotein Increase Circulating Nuclear Factor-Kappa B Activation in Patients With Unstable Angina

Luciano Cominacini, MD^_*,_*, Maurizio Anselmi, MD, Ulisse Garbin, MD^_*, Anna Fratta Pasini, MD^_*, Chiara Stranieri, BSc, PhD^_*, Massimiliano Fusaro, MD, Cristina Nava, MD^_*, Pierfrancesco Agostoni, MD, Dritan Keta, MD, Pietro Zardini, MD, Tatsuya Sawamura, MD, PhD and Vincenzo Lo Cascio, MD^_*

^_* Department of Biomedical and Surgical Sciences, Section of Internal Medicine, University of Verona, Verona, Italy
Section of Cardiology, University of Verona, Verona, Italy
Department of Bioscience, National Cardiovascular Center Research Institute, Osaka, Japan

Manuscript received January 19, 2005; revised manuscript received March 7, 2005, accepted May 9, 2005.

^_* Reprint requests and correspondence: Dr. Luciano Cominacini, Dipartimento di Scienze Biomediche e Chirurgiche, Sezione di Medicina Interna D - Università di Verona, Policlinico G.B. Rossi - P.le L.A. Scuro 10, 37134 Verona, Italy (Email: luciano.cominacini{at}univr.it).

OBJECTIVES: The purpose of this study was to investigate the effect of circulating levels of oxidized low-density lipoprotein (ox-LDL) on nuclear factor-kappa B (NF-kB) activation in peripheral blood mononuclear cells (PBMC) of patients with unstable angina (UA) or stable angina (SA) and control subjects.

BACKGROUND: Nuclear factor-kB might be involved in atherosclerosis, as is suggested by the presence of activated NF-kB in human atherosclerotic lesions.

METHODS: Levels of plasma ox-LDL and circulating NF-kB in PBMC (and in separated lymphocytes and monocytes) were measured in 27 control subjects and 29 SA and 27 UA patients. In in vitro studies, the effect of ox-LDL and of the sera derived from a subgroup of UA patients and control subjects on monocytic NF-kB activation was also evaluated.

RESULTS: The UA and SA patients had higher levels of circulating ox-LDL and NF-kB in PBMC than control subjects (p < 0.001). The increase in circulating NF-kB was mainly due to the activation of monocytes. In the in vitro studies, ox-LDL dose-dependently increased the activation of NF-kB in monocytes, but not in lymphocytes derived from healthy volunteers. This increase was related to the expression of lectin-like ox-LDL receptor-1 on monocytes. The incubation of monocytes with the sera derived from the UA patients induced a significant increase in NF-kB activation compared with the sera derived from the control subjects.

CONCLUSIONS: The data suggest that the activation of NF-kB in monocytes of UA patients is, at least in part, induced by circulating molecules such as ox-LDL, which has been found to be particularly elevated in UA patients.

Abbreviations and Acronyms   ACS = acute coronary syndrome   CAD = coronary artery disease   HDL = high-density lipoprotein   IgG = immunoglobulin G   LOX-1 = lectin-like ox-LDL receptor-1   LPDS = lipoprotein-depleted serum   mAb = monoclonal antibody   mRNA = messenger ribonucleic acid   NF-kB = nuclear factor-kappa B   ox-LDL = oxidized low-density lipoprotein   PBMC = peripheral blood mononuclear cells   PCI = percutaneous coronary intervention   RT-PCR = reverse transcriptase-polymerase chain reaction   SA = stable angina   UA = unstable angina

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