6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Intimal hyperplasia induced by vascular intervention causes lipoprotein retention and accelerated atherosclerosis

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Accelerated atherosclerosis diminishes the long term patency of vascular interventions, such as percutaneous coronary intervention and implantation of saphenous vein grafts. However, the cause of this accelerated atherosclerosis is unclear. In this study, we tested the hypothesis that intimal hyperplasia formed following vascular intervention promotes retention of atherogenic lipoproteins. Intimal hyperplasia was surgically induced in the mouse common carotid artery. The surgery was combined with different mouse models of hypercholesterolemia to obtain different cholesterol levels and to control the onsets of hypercholesterolemia. Three weeks after surgery, samples were immunostained for apoB lipoproteins, smooth muscle cells and leukocytes. Already at mild hypercholesterolemia (193 mg/dL), pronounced apoB lipoprotein retention was found in the extracellular matrix in both intimal hyperplasia and the injured underlying media. In contrast, minimal retention was detected in the uninjured proximal region of the same vessel, or in vessels from mice with normal cholesterol levels (81 mg/dL). Induction of aggravated hypercholesterolemia 3 weeks after surgery, when a mature intimal hyperplasia had been formed, caused a very rapid development of atherosclerotic lesions. Mechanistically, we show that lipoprotein retention was almost exclusively dependent on electrostatic interactions to proteoglycan glycosaminoglycans, and the lipoprotein retention to intimal hyperplasia could be inhibited in vivo using glycosaminoglycan‐binding antibodies. Thus, formation of intimal hyperplasia following vascular intervention makes the vessel wall highly susceptible for lipoprotein retention and accelerated atherosclerosis. The increased lipoprotein retention in intimal hyperplasia can be targeted by blocking the interaction between apoB lipoproteins and glycosaminoglycans in the extracellular matrix.

          Related collections

          Most cited references29

          • Record: found
          • Abstract: not found
          • Article: not found

          The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum.

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Subendothelial retention of atherogenic lipoproteins in early atherosclerosis.

            Complications of atherosclerosis are the most common cause of death in Western societies. Among the many risk factors identified by epidemiological studies, only elevated levels of lipoproteins containing apolipoprotein (apo) B can drive the development of atherosclerosis in humans and experimental animals even in the absence of other risk factors. However, the mechanisms that lead to atherosclerosis are still poorly understood. We tested the hypothesis that the subendothelial retention of atherogenic apoB-containing lipoproteins is the initiating event in atherogenesis. The extracellular matrix of the subendothelium, particularly proteoglycans, is thought to play a major role in the retention of atherogenic lipoproteins. The interaction between atherogenic lipoproteins and proteoglycans involves an ionic interaction between basic amino acids in apoB100 and negatively charged sulphate groups on the proteoglycans. Here we present direct experimental evidence that the atherogenicity of apoB-containing low-density lipoproteins (LDL) is linked to their affinity for artery wall proteoglycans. Mice expressing proteoglycan-binding-defective LDL developed significantly less atherosclerosis than mice expressing wild-type control LDL. We conclude that subendothelial retention of apoB100-containing lipoprotein is an early step in atherogenesis.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Pathophysiology of native coronary, vein graft, and in-stent atherosclerosis.

              Plaque rupture, usually of a precursor lesion known as a 'vulnerable plaque' or 'thin-cap fibroatheroma', is the leading cause of thrombosis. Less-frequent aetiologies of coronary thrombosis are erosion, observed with greatest incidence in women aged <50 years, and eruptive calcified nodules, which are occasionally identified in older individuals. Various treatments for patients with coronary artery disease, such as CABG surgery and interventional therapies, have led to accelerated atherosclerosis. These processes occur within months to years, compared with the decades that it generally takes for native disease to develop. Morphological identifiers of accelerated atherosclerosis include macrophage-derived foam cells, intraplaque haemorrhage, and thin fibrous cap. Foam-cell infiltration can be observed within 1 year of a saphenous vein graft implantation, with subsequent necrotic core formation and rupture ensuing after 7 years in over one-third of patients. Neoatherosclerosis occurs early and with greater prevalence in drug-eluting stents than in bare-metal stents and, although rare, complications of late stent thrombosis from rupture are associated with high mortality. Comparison of lesion progression in native atherosclerotic disease, atherosclerosis in saphenous vein grafts, and in-stent neoatherosclerosis provides insight into the pathogenesis of atheroma formation in natural and iatrogenic settings.
                Bookmark

                Author and article information

                Contributors
                per.fogelstrand@wlab.gu.se
                Journal
                Physiol Rep
                Physiol Rep
                10.1002/(ISSN)2051-817X
                PHY2
                physreports
                Physiological Reports
                John Wiley and Sons Inc. (Hoboken )
                2051-817X
                17 July 2017
                July 2017
                : 5
                : 14 ( doiID: 10.1002/phy2.2017.5.issue-14 )
                : e13334
                Affiliations
                [ 1 ] Department of Molecular and Clinical Medicine Wallenberg Laboratory Institute of Medicine Sahlgrenska Academy at University of Gothenburg Gothenburg Sweden
                [ 2 ] Innovation Managing Direction Center of Molecular Immunology Havana Cuba
                Author notes
                [*] [* ] Correspondence

                Per Fogelstrand, Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, 413 45 Gothenburg, SWEDEN.

                Tel: +46 31 342 2210

                Fax: +46 31 823762

                E‐mail: per.fogelstrand@ 123456wlab.gu.se

                [†]

                Shared senior authorship.

                Article
                PHY213334
                10.14814/phy2.13334
                5532481
                28716818
                b0bae7c3-07d4-417f-a1c8-c204dabd676e
                © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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

                History
                : 30 May 2017
                : 02 June 2017
                Page count
                Figures: 5, Tables: 0, Pages: 12, Words: 6545
                Funding
                Funded by: Swedish Research Council
                Funded by: Swedish Society of Medicine
                Funded by: Swedish Heart‐Lung Foundation
                Funded by: Sahlgrenska University Hospital ALF
                Funded by: Emelle foundation
                Funded by: Magnus Bergvalls foundation
                Categories
                Cardiovascular Conditions, Disorders and Treatments
                Vasculature
                Original Research
                Original Research
                Custom metadata
                2.0
                phy213334
                July 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.1.4 mode:remove_FC converted:28.07.2017

                accelerated atherosclerosis,intimal hyperplasia,lipoprotein retention,vascular intervention

                Comments

                Comment on this article