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      Atherosclerosis and the Capillary Network; Pathophysiology and Potential Therapeutic Strategies

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          Abstract

          Atherosclerosis and associated ischemic organ dysfunction represent the number one cause of mortality worldwide. While the key drivers of atherosclerosis, arterial hypertension, hypercholesterolemia and diabetes mellitus, are well known disease entities and their contribution to the formation of atherosclerotic plaques are intensively studied and well understood, less effort is put on the effect of these disease states on microvascular structure an integrity. In this review we summarize the pathological changes occurring in the vascular system in response to prolonged exposure to these major risk factors, with a particular focus on the differences between these pathological alterations of the vessel wall in larger arteries as compared to the microcirculation. Furthermore, we intend to highlight potential therapeutic strategies to improve microvascular function during atherosclerotic vessel disease.

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          Vascular endothelium, hemodynamics, and the pathobiology of atherosclerosis.

          The localization of atherosclerotic lesion formation to regions of disturbed blood flow associated with certain arterial geometries, in humans and experimental animals, suggests an important role for hemodynamic forces in the pathobiology of atherosclerosis. There is increasing evidence that the vascular endothelium, which is directly exposed to various fluid mechanical forces generated by pulsatile blood flow, can discriminate among these different biomechanical stimuli and transduce them into genetic regulatory programs that modulate endothelial function. In this brief review, we discuss how biomechanical stimuli generated by blood flow can influence endothelial functional phenotypes, and explore the working hypothesis of "atheroprone" hemodynamic environments as "local risk factors" in atherogenesis. In addition, we consider the therapeutic implications of the activation of "atheroprotective genes" and their role as "critical regulatory nodes" in vascular homeostasis. Copyright © 2013 Elsevier Inc. All rights reserved.
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            Metformin reduces endogenous reactive oxygen species and associated DNA damage.

            Pharmacoepidemiologic studies provide evidence that use of metformin, a drug commonly prescribed for type II diabetes, is associated with a substantial reduction in cancer risk. Experimental models show that metformin inhibits the growth of certain neoplasms by cell autonomous mechanisms such as activation of AMP kinase with secondary inhibition of protein synthesis or by an indirect mechanism involving reduction in gluconeogenesis leading to a decline in insulin levels and reduced proliferation of insulin-responsive cancers. Here, we show that metformin attenuates paraquat-induced elevations in reactive oxygen species (ROS), and related DNA damage and mutations, but has no effect on similar changes induced by H(2)0(2), indicating a reduction in endogenous ROS production. Importantly, metformin also inhibited Ras-induced ROS production and DNA damage. Our results reveal previously unrecognized inhibitory effects of metformin on ROS production and somatic cell mutation, providing a novel mechanism for the reduction in cancer risk reported to be associated with exposure to this drug. 2012 AACR
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              Incidence and predictors of restenosis after coronary stenting in 10 004 patients with surveillance angiography.

              Systematic investigation of restenosis after percutaneous coronary intervention (PCI) with bare metal stents (BMS) or first or second generation drug eluting stents (DES) in large scale, broadly inclusive patient populations undergoing follow-up angiography represents a gap in our scientific knowledge. We investigated the incidence of angiographically proven restenosis and its predictors in patients undergoing PCI with stents.
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                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                24 December 2019
                January 2020
                : 9
                : 1
                : 50
                Affiliations
                [1 ]Klinik & Poliklinik für Innere Medizin I, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; tilman.ziegler@ 123456tum.de (T.Z.); farah.abdel-rahman@ 123456tum.de (F.A.R.); victoria.jurisch@ 123456googlemail.com (V.J.)
                [2 ]DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, 80802 Munich, Germany
                Author notes
                [* ]Correspondence: christian.kupatt@ 123456tum.de ; Tel.: +49-89-4140-9410
                Author information
                https://orcid.org/0000-0002-3611-1218
                Article
                cells-09-00050
                10.3390/cells9010050
                7016600
                31878229
                72580198-e22c-4255-a7ae-d33b5f931767
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 November 2019
                : 21 December 2019
                Categories
                Review

                atherosclerosis,pericyte,raav,capillary,endothelial cells
                atherosclerosis, pericyte, raav, capillary, endothelial cells

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