Atherosclerosis: current pathogenesis and therapeutic options

被引:1815
作者
Weber, Christian [1 ,2 ,3 ]
Noels, Heidi [4 ]
机构
[1] Univ Munich, Inst Cardiovas Prevent, Munich, Germany
[2] Munich Heart Alliance, Munich, Germany
[3] Maastricht Univ, Cardiovasc Res Inst Maastricht, Maastricht, Netherlands
[4] Rhein Westfal Tech Hsch Aachen Univ, Inst Mol Cardiovasc Res, Aachen, Germany
基金
欧洲研究理事会;
关键词
LOW-DENSITY-LIPOPROTEIN; CORONARY-ARTERY-DISEASE; ENDOPLASMIC-RETICULUM STRESS; DENDRITIC CELLS; REDUCES ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION; PROMOTES ATHEROSCLEROSIS; MONOCYTE RECRUITMENT; CHEMOKINE RECEPTORS; PLAQUE-FORMATION;
D O I
10.1038/nm.2538
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Coronary artery disease (CAD) arising from atherosclerosis is a leading cause of death and morbidity worldwide. The underlying pathogenesis involves an imbalanced lipid metabolism and a maladaptive immune response entailing a chronic inflammation of the arterial wall. The disturbed equilibrium of lipid accumulation, immune responses and their clearance is shaped by leukocyte trafficking and homeostasis governed by chemokines and their receptors. New pro- and anti-inflammatory pathways linking lipid and inflammation biology have been discovered, and genetic profiling studies have unveiled variations involved in human CAD. The growing understanding of the inflammatory processes and mediators has uncovered an intriguing diversity of targetable mechanisms that can be exploited to complement lipid-lowering therapies. Here we aim to systematically survey recently identified molecular mechanisms, translational developments and clinical strategies for targeting lipid-related inflammation in atherosclerosis and CAD.
引用
收藏
页码:1410 / 1422
页数:13
相关论文
共 135 条
[51]   CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival [J].
Landsman, Limor ;
Bar-On, Liat ;
Zernecke, Alma ;
Kim, Ki-Wook ;
Krauthgamer, Rita ;
Shagdarsuren, Erdenechimeg ;
Lira, Sergio A. ;
Weissman, Irving L. ;
Weber, Christian ;
Jung, Steffen .
BLOOD, 2009, 113 (04) :963-972
[52]   A New Monocyte Chemotactic Protein-1/Chemokine CC Motif Ligand-2 Competitor Limiting Neointima Formation and Myocardial Ischemia/Reperfusion Injury in Mice [J].
Liehn, Elisa A. ;
Piccinini, Anna-Maria ;
Koenen, Rory R. ;
Soehnlein, Oliver ;
Adage, Tiziana ;
Fatu, Roxana ;
Curaj, Adelina ;
Popescu, Alexandra ;
Zernecke, Alma ;
Kungl, Andreas J. ;
Weber, Christian .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2010, 56 (22) :1847-1857
[53]   Platelet CD40L mediates thrombotic and inflammatory processes in atherosclerosis [J].
Lievens, Dirk ;
Zernecke, Alma ;
Seijkens, Tom ;
Soehnlein, Oliver ;
Beckers, Linda ;
Munnix, Imke C. A. ;
Wijnands, Erwin ;
Goossens, Pieter ;
van Kruchten, Roger ;
Thevissen, Larissa ;
Boon, Louis ;
Flavell, Richard A. ;
Noelle, Randolph J. ;
Gerdes, Norbert ;
Biessen, Erik A. ;
Daemen, Mat J. A. P. ;
Heemskerk, JohanW. M. ;
Weber, Christian ;
Lutgens, Esther .
BLOOD, 2010, 116 (20) :4317-4327
[54]   The multi-functionality of CD40L and its receptor CD40 in atherosclerosis [J].
Lievens, Dirk ;
Eijgelaar, Wouter J. ;
Biessen, Erik A. L. ;
Daemen, Mat J. A. P. ;
Lutgens, Esther .
THROMBOSIS AND HAEMOSTASIS, 2009, 102 (02) :206-214
[55]   Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus - A meta-analysis of randomized trials [J].
Lincoff, A. Michael ;
Wolski, Kathy ;
Nicholls, Stephen J. ;
Nissen, Steven E. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2007, 298 (10) :1180-1188
[56]   Circulating Platelet-Activating Factor Is Primarily Cleared by Transport, Not Intravascular Hydrolysis by Lipoprotein-Associated Phospholipase A2/PAF Acetylhydrolase [J].
Liu, Jinbo ;
Chen, Rui ;
Marathe, Gopal K. ;
Febbraio, Maria ;
Zou, Weilin ;
McIntyre, Thomas M. .
CIRCULATION RESEARCH, 2011, 108 (04) :469-U155
[57]   CX3CR1 deficiency impairs dendritic cell accumulation in arterial intima and reduces atherosclerotic burden [J].
Liu, Peng ;
Yu, Yen-Rei A. ;
Spencer, Jessica A. ;
Johnson, Ashley E. ;
Vallanat, Christopher T. ;
Fong, Alan M. ;
Patterson, Cam ;
Patel, Dhavalkumar D. .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2008, 28 (02) :243-250
[58]   Chemokine Receptor 7 Knockout Attenuates Atherosclerotic Plaque Development [J].
Luchtefeld, Maren ;
Grothusen, Christina ;
Gagalick, Andreas ;
Jagavelu, Kumaravelu ;
Schuett, Harald ;
Tietge, Uwe J. F. ;
Pabst, Oliver ;
Grote, Karsten ;
Drexler, Helmut ;
Foerster, Reinhold ;
Schieffer, Bernhard .
CIRCULATION, 2010, 122 (16) :1621-U166
[59]   Linking immune-mediated arterial inflammation and cholesterol-induced atherosclerosis in a transgenic mouse model [J].
Ludewig, B ;
Freigang, S ;
Jäggi, M ;
Kurrer, MO ;
Pei, YC ;
Vlk, L ;
Odermatt, B ;
Zinkernagel, RM ;
Hengartner, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (23) :12752-12757
[60]   Nicotinic acid inhibits progression of atherosclerosis in mice through its receptor GPR109A expressed by immune cells [J].
Lukasova, Martina ;
Malaval, Camille ;
Gille, Andreas ;
Kero, Jukka ;
Offermanns, Stefan .
JOURNAL OF CLINICAL INVESTIGATION, 2011, 121 (03) :1163-1173