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      Interaction between dyslipidaemia, oxidative stress and inflammatory response in patients with angiographically proven coronary artery disease

      research-article
      , MBBS, MD , MBBS, MD, DNB , MBBS , MBBS, MD, , MBBS, MD, DM
      Cardiovascular Journal of Africa
      Clinics Cardive Publishing
      nitric oxide, ferritin, apolipoprotein B, coronary artery disease

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          Abstract

          Introduction

          Coronary artery disease (CAD) is emerging as the biggest killer of the 21st century. A number of theories have been postulated to explain the aetiology of atherosclerosis. The present study attempts to elucidate the interaction, if any, between inflammation, oxidative stress and dyslipidaemia in CAD.

          Methods

          A total of 753 patients undergoing angiography were evaluated and 476 were included in the study. The parameters studied included complete lipid profile, and apolipoprotein B, ferritin and nitric oxide (NO) levels. Statistical analysis was carried out to determine the interrelationship between these parameters and the best predictor of CAD risk. Cut-off points were determined from the receiver operating characteristics curves, and the specificity, sensitivity, positive predictive value, negative predictive value, odds ratio and confidence intervals were calculated.

          Results

          The levels of the parameters studied increased with the stenotic state and a positive correlation was observed between ferritin, NO and apolipoprotein B. NO emerged as the most reliable predictor of CAD, with an area under the curve of 0.992 and sensitivity and specificity of 97 and 98%, respectively.

          Conclusion

          Environmental and genetic risk factors for CAD interact in a highly complex manner to initiate the atherosclerotic process. These risk factors should be considered mutually inclusive, not exclusive when devising pharmacological interventions, as multi-factorial risk management is the cornerstone of CAD management

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          Most cited references33

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          Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study

          The Lancet, 349(9064), 1498-1504
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            Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly.

            Nitric oxide contrasts with most intercellular messengers because it diffuses rapidly and isotropically through most tissues with little reaction but cannot be transported through the vasculature due to rapid destruction by oxyhemoglobin. The rapid diffusion of nitric oxide between cells allows it to locally integrate the responses of blood vessels to turbulence, modulate synaptic plasticity in neurons, and control the oscillatory behavior of neuronal networks. Nitric oxide is not necessarily short lived and is intrinsically no more reactive than oxygen. The reactivity of nitric oxide per se has been greatly overestimated in vitro because no drain is provided to remove nitric oxide. Nitric oxide persists in solution for several minutes in micromolar concentrations before it reacts with oxygen to form much stronger oxidants like nitrogen dioxide. Nitric oxide is removed within seconds in vivo by diffusion over 100 microns through tissues to enter red blood cells and react with oxyhemoglobin. The direct toxicity of nitric oxide is modest but is greatly enhanced by reacting with superoxide to form peroxynitrite (ONOO-). Nitric oxide is the only biological molecule produced in high enough concentrations to out-compete superoxide dismutase for superoxide. Peroxynitrite reacts relatively slowly with most biological molecules, making peroxynitrite a selective oxidant. Peroxynitrite modifies tyrosine in proteins to create nitrotyrosines, leaving a footprint detectable in vivo. Nitration of structural proteins, including neurofilaments and actin, can disrupt filament assembly with major pathological consequences. Antibodies to nitrotyrosine have revealed nitration in human atherosclerosis, myocardial ischemia, septic and distressed lung, inflammatory bowel disease, and amyotrophic lateral sclerosis.
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              Myeloperoxidase-generated reactive nitrogen species convert LDL into an atherogenic form in vitro.

              Oxidized LDL is implicated in atherosclerosis; however, the pathways that convert LDL into an atherogenic form in vivo are not established. Production of reactive nitrogen species may be one important pathway, since LDL recovered from human atherosclerotic aorta is enriched in nitrotyrosine. We now report that reactive nitrogen species generated by the MPO-H2O2-NO2- system of monocytes convert LDL into a form (NO2-LDL) that is avidly taken up and degraded by macrophages, leading to massive cholesterol deposition and foam cell formation, essential steps in lesion development. Incubation of LDL with isolated MPO, an H2O2-generating system, and nitrite (NO2-)-- a major end-product of NO metabolism--resulted in nitration of apolipoprotein B 100 tyrosyl residues and initiation of LDL lipid peroxidation. The time course of LDL protein nitration and lipid peroxidation paralleled the acquisition of high-affinity, concentration-dependent, and saturable binding of NO2-LDL to human monocyte-derived macrophages and mouse peritoneal macrophages. LDL modification and conversion into a high-uptake form occurred in the absence of free metal ions, required NO2-, occurred at physiological levels of Cl-, and was inhibited by heme poisons, catalase, and BHT. Macrophage binding of NO2-LDL was specific and mediated by neither the LDL receptor nor the scavenger receptor class A type I. Exposure of macrophages to NO2-LDL promoted cholesteryl ester synthesis, intracellular cholesterol and cholesteryl ester accumulation, and foam cell formation. Collectively, these results identify MPO-generated reactive nitrogen species as a physiologically plausible pathway for converting LDL into an atherogenic form.
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                Author and article information

                Contributors
                Journal
                Cardiovasc J Afr
                Cardiovasc J Afr
                TBC
                Cardiovascular Journal of Africa
                Clinics Cardive Publishing
                1995-1892
                1680-0745
                February 2012
                : 23
                : 1
                : 23-27
                Affiliations
                Department of Biochemistry, GB Pant Hospital, New Delhi, India
                Department of Biochemistry, GB Pant Hospital, New Delhi, India
                Department of Biochemistry, GB Pant Hospital, New Delhi, India
                Department of Biochemistry, GB Pant Hospital, New Delhi, India
                Department of Cardiology, GB Pant Hospital, New Delhi, India
                Article
                10.5830/CVJA-2010-092
                3721930
                22331247
                b90edbfa-3f05-4a25-9104-17ba0ac8a710
                Copyright © 2010 Clinics Cardive Publishing

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 March 2010
                : 26 November 2010
                Categories
                Cardiovascular Topics

                nitric oxide,ferritin,apolipoprotein b,coronary artery disease

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