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      The role of monocyte phenotype switching in peri-procedural myocardial injury and its involvement in statin therapy

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          Abstract

          Peri-procedural myocardial injury, which is associated with worse long-term clinical outcome, is a common complication related to inflammatory pathogenetic mechanisms. Monocytes and macrophages play key roles in the initiation and progression of atherosclerosis. Recent studies have demonstrated that monocytes in human peripheral blood are heterogeneous, including CD14 +CD16 monocytes and CD14 +CD16 + monocytes. Several lines of evidence suggested that CD14 +CD16 + monocytes might contribute to the accelerated atherosclerosis. In view of the heightened appreciation of the heterogeneity of circulating monocytes, we hypothesized that an up-shifting subset of CD14 +CD16 + monocytes might be induced by percutaneous coronary intervention (PCI), which subsequently leads to peri-procedural myocardial injury. Moreover, statins loading before PCI could exert anti-inflammatory effects partly by modulating monocyte phenotype and thus prevent peri-procedural myocardial injury.

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          Most cited references43

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          The CD14+ CD16+ blood monocytes: their role in infection and inflammation.

          Blood monocyte subpopulations have been defined in man initially, and the two major types of monocytes are the CD14++ CD16- and the CD14+ CD16+ monocytes. These cells have been shown to exhibit distinct phenotype and function, and the CD14+ CD16+ were labeled proinflammatory based on higher expression of proinflammatory cytokines and higher potency in antigen presentation. The current review describes these properties, including the relationship to dendritic cells, and summarizes the host of publications about CD14+ CD16+ monocytes in inflammation and infectious disease in man, all of which suggest a crucial role of these cells in the disease processes. The review also covers the more recent description of homologues of these cells in other model species, which is expected to better define the role of monocyte subsets in disease.
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            Therapeutic siRNA silencing in inflammatory monocytes

            Inflammatory monocytes -- but not the non-inflammatory subset -- depend on the chemokine receptor CCR2 for distribution to injured tissue and stimulate disease progression. Precise therapeutic targeting of this inflammatory monocyte subset could spare innate immunity's essential functions for maintenance of homeostasis and thus limit unwanted effects. Here we developed siRNA nanoparticles targeting CCR2 expression in inflammatory monocytes. We identified an optimized lipid nanoparticle and silencing siRNA sequence that when administered systemically, had rapid blood clearance, accumulated in spleen and bone marrow and showed high cellular localization of fluorescently tagged siRNA inside monocytes. Efficient degradation of CCR2 mRNA in monocytes prevented their accumulation in sites of inflammation. Specifically, the treatment attenuated their number in atherosclerotic plaques, reduced infarct size following coronary artery occlusion, prolonged normoglycemia in diabetic mice after pancreatic islet transplantation and resulted in reduced tumor volumes and lower numbers of tumor-associated macrophages. Taken together, siRNA nanoparticle-mediated CCR2 gene silencing in leukocytes selectively modulates functions of innate immune cell subtypes and may allow for the development of specific anti-inflammatory therapy.
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              Macrophage diversity and polarization in atherosclerosis: a question of balance.

              Diversity and plasticity are hallmarks of mononuclear phagocytes, which are reflected in plaque formation and evolution. Different monocyte subsets, which differentially contribute to plaque infiltration and to atherosclerosis complications, have been identified. Similarly, depending on different environmental signals plaque-associated macrophages can express polarized pro- and antiatherogenic programs by influencing lipid metabolism, inflammatory responses, and plaque stability. Thus, a "macrophage balance" plays a major role in the pathogenesis of atherosclerotic plaques and affects evolution and complications of atherosclerosis.
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                Author and article information

                Journal
                Med Sci Monit
                Med. Sci. Monit
                Medical Science Monitor
                Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                International Scientific Literature, Inc.
                1234-1010
                1643-3750
                2013
                17 November 2013
                : 19
                : 1006-1012
                Affiliations
                [1 ]Department of Cardiology, Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
                [2 ]Biological Engineering and Bindley Bioscience Center, Purdue University, West Lafayette, IN, U.S.A.
                Author notes
                Corresponding Author: Dao-Quan Peng, e mail: pengdq@ 123456hotmail.com
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Article
                889661
                10.12659/MSM.889661
                3843601
                24241246
                686a6099-d79f-42ec-b632-52122fb5a514
                © Med Sci Monit, 2013

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License

                History
                : 07 August 2013
                : 30 September 2013
                Categories
                Hypothesis

                monocyte subsets,inflammation,peri-procedural myocardial injury,statin

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