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DOI: 10.1055/s-0042-119649
Circulating Levels of LAMP2 in Coronary Artery Disease: Association with Serum Lipid Profile
Publication History
received 20 March 2016
accepted 17 October 2016
Publication Date:
06 December 2016 (online)
Abstract
Whereas several in vitro and in vivo studies have described the role of lysosomal associated membrane protein 2 (LAMP2) in lipid homeostasis, there is no study addressing LAMP2 serum concentration and its association with lipid profiles in the context of coronary artery disease (CAD). We aimed to determine the LAMP2 serum concentration and its association with serum lipid profiles as well as the gene expression of LAMP2 in peripheral blood mononuclear cells (PBMCs) of CAD patients and control group. Circulating levels of LAMP2 were quantified by enzyme-linked immunosorbent assay (ELISA) in CAD patients (n=85) and control group (n=65) and correlation to lipid parameters was assessed. Gene expression analysis was performed by quantitative real-time PCR. Mean LAMP2 serum concentration adjusted for drug consumption, age and gender was not significantly different between the CAD and control groups (p>0.05). However, LAMP2 serum concentration showed independent significant association with lipid profiles including triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) (all p<0.05). Furthermore, increased expression of LAMP2 has been observed in PBMCs of CAD patients compared to the control group (p<0.05). Our findings supported the previous observations showing the contribution of LAMP2 in lipid homeostasis and pathogenesis of CAD.
* These authors contributed equally to this work
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References
- 1 Schulz C, Massberg S. Atherosclerosis—multiple pathways to lesional macrophages. Sci Transl Med 2014; 6: (239):-239ps2
- 2 Galkina E, Ley K. Immune and inflammatory mechanisms of atherosclerosis. Ann Rev Immunol 2009; 27: 165
- 3 Libby P. Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol 2012; 32: 2045-2051
- 4 Falk E. Pathogenesis of atherosclerosis. J Am Coll Cardiol 2006; 47: C7-C12
- 5 Lusis AJ. Atherosclerosis. Nature 2000; 407: 233-241
- 6 Ghosh S. Macrophage cholesterol homeostasis and metabolic diseases: critical role of cholesteryl ester mobilization. Exp Rev Cardiovasc Ther 2011; 9: 329-340
- 7 Jerome WG. Lysosomes, cholesterol and atherosclerosis. Clin Lipidol 2010; 5: 853-865
- 8 Bobryshev YV, Shchelkunova TA, Morozov IA, Rubtsov PM, Sobenin IA, Orekhov AN, Smirnov AN. Changes of lysosomes in the earliest stages of the development of atherosclerosis. J Cell Mol Med 2013; 17: 626-635
- 9 Cazarin J, Andrade B, Carvalho D. AMP-Activated Protein Kinase Activation Leads to Lysome-Mediated NA+/Iˉ-Symporter Protein Degradation in Rat Thyroid Cells. Horm Metab Res 2014; 46: 313-317
- 10 Jerome WG, Cox BE, Griffin EE, Ullery JC. Lysosomal cholesterol accumulation inhibits subsequent hydrolysis of lipoprotein cholesteryl ester. Microscopy and Microanalysis 2008; 14: 138-149
- 11 Eskelinen E-L, Schmidt CK, Neu S, Willenborg M, Fuertes G, Salvador N, Tanaka Y, Lüllmann-Rauch R, Hartmann D, Heeren J. Disturbed cholesterol traffic but normal proteolytic function in LAMP-1/LAMP-2 double-deficient fibroblasts. Mol Biol Cell 2004; 15: 3132-3145
- 12 Schneede A, Schmidt CK, Hölttä-Vuori M, Heeren J, Willenborg M, Blanz J, Domanskyy M, Breiden B, Brodesser S, Landgrebe J. Role for LAMP-2 in endosomal cholesterol transport. J Cell Mol Med 2011; 15: 280-295
- 13 Huynh KK, Eskelinen EL, Scott CC, Malevanets A, Saftig P, Grinstein S. LAMP proteins are required for fusion of lysosomes with phagosomes. EMBO J 2007; 26: 313-324
- 14 Eskelinen E-L. Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy. Mol Aspect Med 2006; 27: 495-502
- 15 Mavrogeni S, Markousis-Mavrogenis G, Markussis V, Kolovou G. The Emerging Role of Cardiovascular Magnetic Resonance Imaging in the Evaluation of Metabolic Cardiomyopathies. Horm Metab Res 2015; 47: 623-632
- 16 Xia Y, Liu Y, Xia T, Li X, Huo C, Jia X, Wang L, Xu R, Wang N, Zhang M. Activation of volume-sensitive Cl-channel mediates autophagy-related cell death in myocardial ischaemia/reperfusion injury. Oncotarget 2016; DOI: 10.18632/oncotarget.10050. [Epub ahead of print]
- 17 Giegerich AK, Kuchler L, Sha LK, Knape T, Heide H, Wittig I, Behrends C, Brüne B, Knethen Av. Autophagy-dependent PELI3 degradation inhibits proinflammatory IL1B expression. Autophagy 2014; 10: 1937-1952
- 18 Sala G, Stefanoni G, Arosio A, Riva C, Melchionda L, Saracchi E, Fermi S, Brighina L, Ferrarese C. Reduced expression of the chaperone-mediated autophagy carrier hsc70 protein in lymphomonocytes of patients with Parkinson’s disease. Brain Res 2014; 1546: 46-52
- 19 Corrales J, Almeida M, Martín-Martín L, Miralles J, Orfao A. Testosterone replacement therapy in hypogonadal men is associated with increased expression of LAMP-2 (CD107b) by circulating monocytes and dendritic cells. Clin Endocrinol 2014; 80: 577-584
- 20 Kannan K, Stewart RM, Bounds W, Carlsson SR, Fukuda M, Betzing KW, Holcombe RF. Lysosome-associated membrane proteins h-LAMP1 (CD107a) and h-LAMP2 (CD107b) are activation-dependent cell surface glycoproteins in human peripheral blood mononuclear cells which mediate cell adhesion to vascular endothelium. Cell Immunol 1996; 171: 10-19
- 21 Wang L, Guo G-y, Wang J-b, Zhou X-m, Yang Q, Han Z-y, Li Q, Zhang J-w, Cai Y, Ren X-l. A decline of LAMP-2 predicts ursodeoxycholic acid response in primary biliary cirrhosis. Sci Rep 2015; 5: 9772
- 22 Blond E, Rieusset J, Alligier M, Lambert-Porcheron S, Bendridi N, Gabert L, Chetiveaux M, Debard C, Chauvin M-A, Normand S. Nicotinic acid effects on insulin sensitivity and hepatic lipid metabolism: an in vivo to in vitro study. Horm Metab Res 2014; 46: 390-396
- 23 Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science 1986; 232: 34-47
- 24 Wu G, Huang J, Wei G, Liu L, Pang S, Yan B. LAMP-2 Gene Expression in Peripheral Leukocytes Is Increased in Patients With Coronary Artery Disease. Clin Cardiol 2011; 34: 239-243
- 25 Yang S, Xia C, Li S, Du L, Zhang L, Hu Y. Mitochondrial dysfunction driven by the LRRK2-mediated pathway is associated with loss of Purkinje cells and motor coordination deficits in diabetic rat model. Cell Death Dis 2014; 5: e1217