Endothelial cell metabolism in normal and diseased vasculature

Circulation Research

Volumn 116, Issue 7, 2015, Pages 1231-1244

  Eelen, Guy ^a,b   De Zeeuw, Pauline ^a,b   Simons, Michael ^c   Carmeliet, Peter ^a,b  

^a UNIVERSITY OF LEUVEN   (Belgium)

^b DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^c YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Angiogenesis; Atherosclerosis; Cancer; Diabetes mellitus; Endothelial metabolism

Indexed keywords

ANGIOGENESIS; ATHEROSCLEROSIS; CELL METABOLISM; CELLS BY BODY ANATOMY; CYTOLOGY; DIABETES MELLITUS; ENDOTHELIUM CELL; HUMAN; NERVE SPROUTING; NONHUMAN; PRIORITY JOURNAL; REVIEW; SHEAR STRESS; TUMOR VASCULARIZATION; VASCULAR DISEASE; VASCULAR TUMOR; CELL MOTION; CLASSIFICATION; DIABETIC ANGIOPATHY; ENERGY METABOLISM; METABOLISM; MORPHOGENESIS; NEOPLASM; NEOVASCULARIZATION (PATHOLOGY); OXIDATIVE STRESS; PATHOLOGY; PHYSIOLOGY; STROMA CELL; TRANSLATIONAL RESEARCH; TUMOR MICROENVIRONMENT; VASCULAR ENDOTHELIUM; VASCULARIZATION;

ADVANCED GLYCATION END PRODUCT; AMINO ACID; FATTY ACID; GLUCOSE; NITRIC OXIDE; REACTIVE OXYGEN METABOLITE;

AMINO ACIDS; ATHEROSCLEROSIS; CELL MOVEMENT; DIABETIC ANGIOPATHIES; ENDOTHELIAL CELLS; ENDOTHELIUM, VASCULAR; ENERGY METABOLISM; FATTY ACIDS; GLUCOSE; GLYCOSYLATION END PRODUCTS, ADVANCED; HUMANS; MORPHOGENESIS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; NEOVASCULARIZATION, PHYSIOLOGIC; NITRIC OXIDE; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES; STROMAL CELLS; TRANSLATIONAL MEDICAL RESEARCH; TUMOR MICROENVIRONMENT; VASCULAR DISEASES;

EID: 84935082524     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.116.302855     Document Type: Review

References (144)

1. Carmeliet P, Jain RK, Molecular mechanisms and clinical applications of angiogenesis. Nature 2011; 473: 298-307. doi: 10.1038/nature10144.
2. Tammela T, Alitalo K, Lymphangiogenesis: molecular mechanisms and future promise. Cell 2010; 140: 460-476. doi: 10.1016/j.cell.2010.01.045.
3. Potente M, Gerhardt H, Carmeliet P, Basic and therapeutic aspects of angiogenesis. Cell 2011; 146: 873-887. doi: 10.1016/j.cell.2011.08.039.
4. Mazzone M, Dettori D, Leite de Oliveira R, Heterozygous deficiency of phd2 restores tumor oxygenation and inhibits metastasis via endothelial normalization. Cell 2009; 136: 839-851. doi: 10.1016/j.cell.2009.01.020.
5. Phng LK, Gerhardt H, Angiogenesis: a team effort coordinated by notch. Dev Cell 2009; 16: 196-208. doi: 10.1016/j.devcel.2009.01.015.
6. Jakobsson L, Franco CA, Bentley K, Collins RT, Ponsioen B, Aspalter IM, Rosewell I, Busse M, Thurston G, Medvinsky A, Schulte-Merker S, Gerhardt H, Endothelial cells dynamically compete for the tip cell position during angiogenic sprouting. Nat Cell Biol 2010; 12: 943-953. doi: 10.1038/ncb2103.
7. Gaengel K, Genové G, Armulik A, Betsholtz C, Endothelial-mural cell signaling in vascular development and angiogenesis. Arterioscler Thromb Vasc Biol 2009; 29: 630-638. doi: 10.1161/ATVBAHA.107.161521.
8. Groschner LN, Waldeck-Weiermair M, Malli R, Graier WF, Endothelial mitochondria-less respiration, more integration. Pflugers Arch 2012; 464: 63-76. doi: 10.1007/s00424-012-1085-z.
9. Dagher Z, Ruderman N, Tornheim K, Ido Y, Acute regulation of fatty acid oxidation and amp-activated protein kinase in human umbilical vein endothelial cells. Circ Res 2001 88 1276 1282
10. De Bock K, Georgiadou M, Schoors S, Role of pfkfb3-driven glycolysis in vessel sprouting. Cell 2013; 154: 651-663. doi: 10.1016/j.cell.2013.06.037.
11. Mertens S, Noll T, Spahr R, Krützfeldt A, Piper HM, Energetic response of coronary endothelial cells to hypoxia. Am J Physiol 1990 258 H689 H694
12. Ghesquière B, Wong BW, Kuchnio A, Carmeliet P, Metabolism of stromal and immune cells in health and disease. Nature 2014; 511: 167-176. doi: 10.1038/nature13312.
13. Schoors S, De Bock K, Cantelmo AR, Partial and transient reduction of glycolysis by pfkfb3 blockade reduces pathological angiogenesis. Cell metabolism 2014; 19: 37-48. doi: 10.1016/j.cmet.2013.11.008.
14. Doddaballapur A, Michalik KM, Manavski Y, Lucas T, Houtkooper RH, You X, Chen W, Zeiher AM, Potente M, Dimmeler S, Boon RA, Laminar shear stress inhibits endothelial cell metabolism via KLF2-mediated repression of PFKFB3. Arterioscler Thromb Vasc Biol 2015; 35: 137-145. doi: 10.1161/ATVBAHA.114.304277.
15. Slawson C, Copeland RJ, Hart GW, O-GlcNAc signaling: a metabolic link between diabetes and cancer? Trends Biochem Sci 2010; 35: 547-555. doi: 10.1016/j.tibs.2010.04.005.
16. Benedito R, Roca C, Sörensen I, Adams S, Gossler A, Fruttiger M, Adams RH, The notch ligands Dll4 and Jagged1 have opposing effects on angiogenesis. Cell 2009; 137: 1124-1135. doi: 10.1016/j.cell.2009.03.025.
17. Vaisman N, Gospodarowicz D, Neufeld G, Characterization of the receptors for vascular endothelial growth factor. J Biol Chem 1990 265 19461 19466
18. Merchan JR, Kovács K, Railsback JW, Kurtoglu M, Jing Y, Piña Y, Gao N, Murray TG, Lehrman MA, Lampidis TJ, Antiangiogenic activity of 2-deoxy-D-glucose. PLoS One 2010 5 e13699. doi: 10.1371/journal.pone.0013699.
19. Riganti C, Gazzano E, Polimeni M, Aldieri E, Ghigo D, The pentose phosphate pathway: an antioxidant defense and a crossroad in tumor cell fate. Free Radic Biol Med 2012; 53: 421-436. doi: 10.1016/j.freeradbiomed.2012.05.006.
20. Vizán P, Sánchez-Tena S, Alcarraz-Vizán G, Soler M, Messeguer R, Pujol MD, Lee WN, Cascante M, Characterization of the metabolic changes underlying growth factor angiogenic activation: identification of new potential therapeutic targets. Carcinogenesis 2009; 30: 946-952. doi: 10.1093/carcin/bgp083.
21. Zhang Z, Apse K, Pang J, Stanton RC, High glucose inhibits glucose-6-phosphate dehydrogenase via cAMP in aortic endothelial cells. J Biol Chem 2000; 275: 40042-40047. doi: 10.1074/jbc.M007505200.
22. Elmasri H, Karaaslan C, Teper Y, Ghelfi E, Weng M, Ince TA, Kozakewich H, Bischoff J, Cataltepe S, Fatty acid binding protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells. FASEB J 2009; 23: 3865-3873. doi: 10.1096/fj.09-134882.
23. Carracedo A, Cantley LC, Pandolfi PP, Cancer metabolism: fatty acid oxidation in the limelight. Nat Rev Cancer 2013; 13: 227-232. doi: 10.1038/nrc3483.
24. Jeon SM, Chandel NS, Hay N, AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature 2012; 485: 661-665. doi: 10.1038/nature11066.
25. Iso T, Maeda K, Hanaoka H, Capillary endothelial fatty acid binding proteins 4 and 5 play a critical role in fatty acid uptake in heart and skeletal muscle. Arterioscler Thromb Vasc Biol 2013; 33: 2549-2557. doi: 10.1161/ATVBAHA.113.301588.
26. Hagberg CE, Falkevall A, Wang X, Vascular endothelial growth factor b controls endothelial fatty acid uptake. Nature 2010; 464: 917-921. doi: 10.1038/nature08945.
27. Kivela R, Bry M, Robciuc MR, Vegf-b-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart. EMBO Mol Med 2014; 6: 307-321. doi: 10.1002/emmm.201303147.
28. Davies BS, Beigneux AP, Barnes RH II, Tu Y, Gin P, Weinstein MM, Nobumori C, Nyrén R, Goldberg I, Olivecrona G, Bensadoun A, Young SG, Fong LG, GPIHBP1 is responsible for the entry of lipoprotein lipase into capillaries. Cell Metab 2010; 12: 42-52. doi: 10.1016/j.cmet.2010.04.016.
29. Tousoulis D, Kampoli AM, Tentolouris C, Papageorgiou N, Stefanadis C, The role of nitric oxide on endothelial function. Curr Vasc Pharmacol 2012 10 4 18
30. DeBerardinis RJ, Cheng T, Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene 2010; 29: 313-324. doi: 10.1038/onc.2009.358.
31. Lohmann R, Souba WW, Bode BP, Rat liver endothelial cell glutamine transporter and glutaminase expression contrast with parenchymal cells. Am J Physiol 1999 276 G743 G750
32. Wu G, Haynes TE, Yan W, Meininger CJ, Presence of glutamine:fructose-6-phosphate amidotransferase for glucosamine-6-phosphate synthesis in endothelial cells: effects of hyperglycaemia and glutamine. Diabetologia 2001; 44: 196-202. doi: 10.1007/s001250051599.
33. Unterluggauer H, Mazurek S, Lener B, Hütter E, Eigenbrodt E, Zwerschke W, Jansen-Dürr P, Premature senescence of human endothelial cells induced by inhibition of glutaminase. Biogerontology 2008; 9: 247-259. doi: 10.1007/s10522-008-9134-x.
34. Gao P, Tchernyshyov I, Chang TC, Lee YS, Kita K, Ochi T, Zeller KI, De Marzo AM, Van Eyk JE, Mendell JT, Dang CV, c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 2009; 458: 762-765. doi: 10.1038/nature07823.
35. Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK, Nissim I, Daikhin E, Yudkoff M, McMahon SB, Thompson CB, Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci U S A 2008; 105: 18782-18787. doi: 10.1073/pnas.0810199105.
36. Hu W, Zhang C, Wu R, Sun Y, Levine A, Feng Z, Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. Proc Natl Acad Sci U S A 2010; 107: 7455-7460. doi: 10.1073/pnas.1001006107.
37. Strasser GA, Kaminker JS, Tessier-Lavigne M, Microarray analysis of retinal endothelial tip cells identifies CXCR4 as a mediator of tip cell morphology and branching. Blood 2010; 115: 5102-5110. doi: 10.1182/blood-2009-07-230284.
38. Amelio I, Cutruzzolá F, Antonov A, Agostini M, Melino G, Serine and glycine metabolism in cancer. Trends Biochem Sci 2014; 39: 191-198. doi: 10.1016/j.tibs.2014.02.004.
39. Mishra RC, Tripathy S, Desai KM, Quest D, Lu Y, Akhtar J, Gopalakrishnan V, Nitric oxide synthase inhibition promotes endothelium-dependent vasodilatation and the antihypertensive effect of L-serine. Hypertension 2008; 51: 791-796. doi: 10.1161/HYPERTENSIONAHA.107.099598.
40. Mishra RC, Tripathy S, Quest D, Desai KM, Akhtar J, Dattani ID, Gopalakrishnan V, L-Serine lowers while glycine increases blood pressure in chronic L-NAME-treated and spontaneously hypertensive rats. J Hypertens 2008 26 2339 2348
41. Tibbetts AS, Appling DR, Compartmentalization of mammalian folate-mediated one-carbon metabolism. Annu Rev Nutr 2010; 30: 57-81. doi: 10.1146/annurev.nutr.012809.104810.
42. Fisslthaler B, Fleming I, Activation and signaling by the AMP-activated protein kinase in endothelial cells. Circ Res 2009; 105: 114-127. doi: 10.1161/CIRCRESAHA.109.201590.
43. Li J, McCullough LD, Effects of AMP-activated protein kinase in cerebral ischemia. J Cereb Blood Flow Metab 2010; 30: 480-492. doi: 10.1038/jcbfm.2009.255.
44. Eijkelenboom A, Burgering BM, FOXOs: signalling integrators for homeostasis maintenance. Nat Rev Mol Cell Biol 2013; 14: 83-97. doi: 10.1038/nrm3507.
45. Mihaylova MM, Shaw RJ, The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat Cell Biol 2011; 13: 1016-1023. doi: 10.1038/ncb2329.
46. Pollizzi KN, Powell JD, Integrating canonical and metabolic signalling programmes in the regulation of T cell responses. Nat Rev Immunol 2014; 14: 435-446. doi: 10.1038/nri3701.
47. Parra-Bonilla G, Alvarez DF, Al-Mehdi AB, Alexeyev M, Stevens T, Critical role for lactate dehydrogenase A in aerobic glycolysis that sustains pulmonary microvascular endothelial cell proliferation. Am J Physiol Lung Cell Mol Physiol 2010 299 L513 L522. doi: 10.1152/ajplung.00274.2009.
48. Tang X, Luo YX, Chen HZ, Liu DP, Mitochondria, endothelial cell function, and vascular diseases. Front Physiol 2014 5 175. doi: 10.3389/fphys.2014.00175.
49. Ohga N, Ishikawa S, Maishi N, Akiyama K, Hida Y, Kawamoto T, Sadamoto Y, Osawa T, Yamamoto K, Kondoh M, Ohmura H, Shinohara N, Nonomura K, Shindoh M, Hida K, Heterogeneity of tumor endothelial cells: comparison between tumor endothelial cells isolated from high- and low-metastatic tumors. Am J Pathol 2012; 180: 1294-1307. doi: 10.1016/j.ajpath.2011.11.035.
50. Aird WC, Endothelial cell heterogeneity. Cold Spring Harb Perspect Med 2012 2 a006429. doi: 10.1101/cshperspect.a006429.
51. Drummond GR, Sobey CG, Endothelial NADPH oxidases: which NOX to target in vascular disease? Trends Endocrinol Metab 2014; 25: 452-463. doi: 10.1016/j.tem.2014.06.012.
52. Du X, Matsumura T, Edelstein D, Rossetti L, Zsengellér Z, Szabó C, Brownlee M, Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells. J Clin Invest 2003; 112: 1049-1057. doi: 10.1172/JCI18127.
53. Lorenzi M, The polyol pathway as a mechanism for diabetic retinopathy: attractive, elusive, and resilient. Exp Diabetes Res 2007 2007 61038. doi: 10.1155/2007/61038.
54. Wautier JL, Schmidt AM, Protein glycation: a firm link to endothelial cell dysfunction. Circ Res 2004; 95: 233-238. doi: 10.1161/01.RES.0000137876.28454.64.
55. Federici M, Menghini R, Mauriello A, Hribal ML, Ferrelli F, Lauro D, Sbraccia P, Spagnoli LG, Sesti G, Lauro R, Insulin-dependent activation of endothelial nitric oxide synthase is impaired by O-linked glycosylation modification of signaling proteins in human coronary endothelial cells. Circulation 2002 106 466 472
56. Das Evcimen N, King GL, The role of protein kinase C activation and the vascular complications of diabetes. Pharmacol Res 2007; 55: 498-510. doi: 10.1016/j.phrs.2007.04.016.
57. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP, Giardino I, Brownlee M, Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000; 404: 787-790. doi: 10.1038/35008121.
58. Brownlee M, The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005 54 1615 1625
59. Goldin A, Beckman JA, Schmidt AM, Creager MA, Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 2006; 114: 597-605. doi: 10.1161/CIRCULATIONAHA.106.621854.
60. Ott C, Jacobs K, Haucke E, Navarrete Santos A, Grune T, Simm A, Role of advanced glycation end products in cellular signaling. Redox Biol 2014; 2: 411-429. doi: 10.1016/j.redox.2013.12.016.
61. Boyle JJ, Macrophage activation in atherosclerosis: pathogenesis and pharmacology of plaque rupture. Curr Vasc Pharmacol 2005 3 63 68
62. Isoda K, Folco EJ, Shimizu K, Libby P, AGE-BSA decreases ABCG1 expression and reduces macrophage cholesterol efflux to HDL. Atherosclerosis 2007; 192: 298-304. doi: 10.1016/j.atherosclerosis.2006.07.023.
63. Chuah YK, Basir R, Talib H, Tie TH, Nordin N, Receptor for advanced glycation end products and its involvement in inflammatory diseases. Int J Inflam 2013 2013 403460. doi: 10.1155/2013/403460.
64. Hu P, Lai D, Lu P, Gao J, He H, ERK and Akt signaling pathways are involved in advanced glycation end product-induced autophagy in rat vascular smooth muscle cells. Int J Mol Med 2012; 29: 613-618. doi: 10.3892/ijmm.2012.891.
65. San Martin A, Foncea R, Laurindo FR, Ebensperger R, Griendling KK, Leighton F, Nox1-based NADPH oxidase-derived superoxide is required for VSMC activation by advanced glycation end-products. Free Radic Biol Med 2007; 42: 1671-1679. doi: 10.1016/j.freeradbiomed.2007.02.002.
66. Sakata N, Meng J, Takebayashi S, Effects of advanced glycation end products on the proliferation and fibronectin production of smooth muscle cells. J Atheroscler Thromb 2000 7 169 176
67. Tanikawa T, Okada Y, Tanikawa R, Tanaka Y, Advanced glycation end products induce calcification of vascular smooth muscle cells through RAGE/p38 MAPK. J Vasc Res 2009; 46: 572-580. doi: 10.1159/000226225.
68. Wang Y, Zhang ZY, Chen XQ, Wang X, Cao H, Liu SW, Advanced glycation end products promote human aortic smooth muscle cell calcification in vitro via activating NF-κB and down-regulating IGF1R expression. Acta Pharmacol Sin 2013; 34: 480-486. doi: 10.1038/aps.2012.166.
69. Wu G, Haynes TE, Li H, Yan W, Meininger CJ, Glutamine metabolism to glucosamine is necessary for glutamine inhibition of endothelial nitric oxide synthesis. Biochem J 2001 353 245 252
70. Koziel A, Woyda-Ploszczyca A, Kicinska A, Jarmuszkiewicz W, The influence of high glucose on the aerobic metabolism of endothelial EA.hy926 cells. Pflugers Arch 2012; 464: 657-669. doi: 10.1007/s00424-012-1156-1.
71. Qi L, Qi Q, Prudente S, Association between a genetic variant related to glutamic acid metabolism and coronary heart disease in individuals with type 2 diabetes. JAMA 2013; 310: 821-828. doi: 10.1001/jama.2013.276305.
72. Ido Y, Carling D, Ruderman N, Hyperglycemia-induced apoptosis in human umbilical vein endothelial cells: inhibition by the AMP-activated protein kinase activation. Diabetes 2002 51 159 167
73. Yamagishi SI, Edelstein D, Du XL, Kaneda Y, Guzmán M, Brownlee M, Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase A. J Biol Chem 2001; 276: 25096-25100. doi: 10.1074/jbc.M007383200.
74. Du X, Edelstein D, Obici S, Higham N, Zou MH, Brownlee M, Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation. J Clin Invest 2006; 116: 1071-1080. doi: 10.1172/JCI23354.
75. Richards OC, Raines SM, Attie AD, The role of blood vessels, endothelial cells, and vascular pericytes in insulin secretion and peripheral insulin action. Endocr Rev 2010; 31: 343-363. doi: 10.1210/er.2009-0035.
76. Lesniewski LA, Donato AJ, Behnke BJ, Woodman CR, Laughlin MH, Ray CA, Delp MD, Decreased NO signaling leads to enhanced vasoconstrictor responsiveness in skeletal muscle arterioles of the ZDF rat prior to overt diabetes and hypertension. Am J Physiol Heart Circ Physiol 2008 294 H1840 H1850. doi: 10.1152/ajpheart.00692.2007.
77. Kawashima S, Malfunction of vascular control in lifestyle-related diseases: endothelial nitric oxide (NO) synthase/NO system in atherosclerosis. J Pharmacol Sci 2004 96 411 419
78. Moncada S, Higgs EA, Hodson HF, Knowles RG, Lopez-Jaramillo P, McCall T, Palmer RM, Radomski MW, Rees DD, Schulz R, The l-arginine: nitric oxide pathway. J Cardiovasc Pharmacol 1991 17 1 9
79. Moncada S, Palmer RM, Higgs EA, Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991 43 109 142
80. Nathan C, Xie QW, Nitric oxide synthases: roles, tolls, and controls. Cell 1994 78 915 918
81. Davignon J, Ganz P, Role of endothelial dysfunction in atherosclerosis. Circulation 2004 109 27 32
82. Kopincová J, Púzserová A, Bernátová I, L-NAME in the cardiovascular system-nitric oxide synthase activator? Pharmacol Rep 2012 64 511 520
83. Stroes E, Hijmering M, van Zandvoort M, Wever R, Rabelink TJ, van Faassen EE, Origin of superoxide production by endothelial nitric oxide synthase. FEBS Lett 1998 438 161 164
84. Castillo L, Chapman TE, Sanchez M, Yu YM, Burke JF, Ajami AM, Vogt J, Young VR, Plasma arginine and citrulline kinetics in adults given adequate and arginine-free diets. Proc Natl Acad Sci U S A 1993 90 7749 7753
85. Böger RH, Bode-Böger SM, Szuba A, Tsao PS, Chan JR, Tangphao O, Blaschke TF, Cooke JP, Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation 1998 98 1842 1847
86. Cooke JP, Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol 2000 20 2032 2037
87. th International Symposium on ADMA. Pharmacol Res 2009 60 447. doi: 10.1016/j.phrs.2009.10.001.
88. Leiper JM, Santa Maria J, Chubb A, MacAllister RJ, Charles IG, Whitley GS, Vallance P, Identification of two human dimethylarginine dimethylaminohydrolases with distinct tissue distributions and homology with microbial arginine deiminases. Biochem J 1999 343 Pt 1 209 214
89. Wilcox CS, Asymmetric dimethylarginine and reactive oxygen species: unwelcome twin visitors to the cardiovascular and kidney disease tables. Hypertension 2012; 59: 375-381. doi: 10.1161/HYPERTENSIONAHA.111.187310.
90. Chan JR, Böger RH, Bode-Böger SM, Tangphao O, Tsao PS, Blaschke TF, Cooke JP, Asymmetric dimethylarginine increases mononuclear cell adhesiveness in hypercholesterolemic humans. Arterioscler Thromb Vasc Biol 2000 20 1040 1046
91. Griendling KK, Sorescu D, Ushio-Fukai M, NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 2000 86 494 501
92. Kawashima S, Yokoyama M, Dysfunction of endothelial nitric oxide synthase and atherosclerosis. Arterioscler Thromb Vasc Biol 2004; 24: 998-1005. doi: 10.1161/01.ATV.0000125114.88079.96.
93. Warnholtz A, Nickenig G, Schulz E, Macharzina R, Bräsen JH, Skatchkov M, Heitzer T, Stasch JP, Griendling KK, Harrison DG, Böhm M, Meinertz T, Münzel T, Increased NADH-oxidase-mediated superoxide production in the early stages of atherosclerosis: evidence for involvement of the renin-angiotensin system. Circulation 1999 99 2027 2033
94. Chuaiphichai S, McNeill E, Douglas G, Crabtree MJ, Bendall JK, Hale AB, Alp NJ, Channon KM, Cell-autonomous role of endothelial GTP cyclohydrolase 1 and tetrahydrobiopterin in blood pressure regulation. Hypertension 2014; 64: 530-540. doi: 10.1161/HYPERTENSIONAHA.114.03089.
95. Crabtree MJ, Smith CL, Lam G, Goligorsky MS, Gross SS, Ratio of 5,6,7,8-tetrahydrobiopterin to 7,8-dihydrobiopterin in endothelial cells determines glucose-elicited changes in NO vs. superoxide production by eNOS. Am J Physiol Heart Circ Physiol 2008 294 H1530 H1540. doi: 10.1152/ajpheart.00823.2007.
96. Bendall JK, Douglas G, McNeill E, Channon KM, Crabtree MJ, Tetrahydrobiopterin in cardiovascular health and disease. Antioxid Redox Signal 2014; 20: 3040-3077. doi: 10.1089/ars.2013.5566.
97. Locasale JW, Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat Rev Cancer 2013; 13: 572-583. doi: 10.1038/nrc3557.
98. Jaffe AB, Hall A, Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol 2005; 21: 247-269. doi: 10.1146/annurev.cellbio.21.020604.150721.
99. Riento K, Ridley AJ, Rocks: multifunctional kinases in cell behaviour. Nat Rev Mol Cell Biol 2003; 4: 446-456. doi: 10.1038/nrm1128.
100. Laufs U, Liao JK, Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. J Biol Chem 1998 273 24266 24271
101. Wilkinson MJ, Laffin LJ, Davidson MH, Overcoming toxicity and side-effects of lipid-lowering therapies. Best Pract Res Clin Endocrinol Metab 2014; 28: 439-452. doi: 10.1016/j.beem.2014.01.006.
102. Rolfe BE, Worth NF, World CJ, Campbell JH, Campbell GR, Rho and vascular disease. Atherosclerosis 2005; 183: 1-16. doi: 10.1016/j.atherosclerosis.2005.04.023.
103. Mugoni V, Postel R, Catanzaro V, De Luca E, Turco E, Digilio G, Silengo L, Murphy MP, Medana C, Stainier DY, Bakkers J, Santoro MM, Ubiad1 is an antioxidant enzyme that regulates eNOS activity by CoQ10 synthesis. Cell 2013; 152: 504-518. doi: 10.1016/j.cell.2013.01.013.
104. Tsai KL, Huang YH, Kao CL, Yang DM, Lee HC, Chou HY, Chen YC, Chiou GY, Chen LH, Yang YP, Chiu TH, Tsai CS, Ou HC, Chiou SH, A novel mechanism of coenzyme Q10 protects against human endothelial cells from oxidative stress-induced injury by modulating NO-related pathways. J Nutr Biochem 2012; 23: 458-468. doi: 10.1016/j.jnutbio.2011.01.011.
105. Urbich C, Dernbach E, Zeiher AM, Dimmeler S, Double-edged role of statins in angiogenesis signaling. Circ Res 2002 90 737 744
106. Tanaka S, Fukumoto Y, Nochioka K, Minami T, Kudo S, Shiba N, Takai Y, Williams CL, Liao JK, Shimokawa H, Statins exert the pleiotropic effects through small GTP-binding protein dissociation stimulator upregulation with a resultant Rac1 degradation. Arterioscler Thromb Vasc Biol 2013; 33: 1591-1600. doi: 10.1161/ATVBAHA.112.300922.
107. Jacobson JR, Statins in endothelial signaling and activation. Antioxid Redox Signal 2009; 11: 811-821. doi: 10.1089/ARS.2008.2284.
108. Margaritis M, Channon KM, Antoniades C, Statins as regulators of redox state in the vascular endothelium: beyond lipid lowering. Antioxid Redox Signal 2014; 20: 1198-1215. doi: 10.1089/ars.2013.5430.
109. Maxfield FR, Tabas I, Role of cholesterol and lipid organization in disease. Nature 2005; 438: 612-621. doi: 10.1038/nature04399.
110. Moore KJ, Tabas I, Macrophages in the pathogenesis of atherosclerosis. Cell 2011; 145: 341-355. doi: 10.1016/j.cell.2011.04.005.
111. Haghpassand M, Bourassa PA, Francone OL, Aiello RJ, Monocyte/macrophage expression of ABCA1 has minimal contribution to plasma HDL levels. J Clin Invest 2001; 108: 1315-1320. doi: 10.1172/JCI12810.
112. Van Eck M, Singaraja RR, Ye D, Hildebrand RB, James ER, Hayden MR, Van Berkel TJ, Macrophage ATP-binding cassette transporter A1 overexpression inhibits atherosclerotic lesion progression in low-density lipoprotein receptor knockout mice. Arterioscler Thromb Vasc Biol 2006; 26: 929-934. doi: 10.1161/01.ATV.0000208364.22732.16.
113. Trigatti B, Rayburn H, Viñals M, Braun A, Miettinen H, Penman M, Hertz M, Schrenzel M, Amigo L, Rigotti A, Krieger M, Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology. Proc Natl Acad Sci U S A 1999 96 9322 9327
114. Wang N, Lan D, Chen W, Matsuura F, Tall AR, ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. Proc Natl Acad Sci U S A 2004; 101: 9774-9779. doi: 10.1073/pnas.0403506101.
115. Fang L, Choi SH, Baek JS, Liu C, Almazan F, Ulrich F, Wiesner P, Taleb A, Deer E, Pattison J, Torres-Vázquez J, Li AC, Miller YI, Control of angiogenesis by AIBP-mediated cholesterol efflux. Nature 2013; 498: 118-122. doi: 10.1038/nature12166.
116. Curry FE, Adamson RH, Endothelial glycocalyx: permeability barrier and mechanosensor. Ann Biomed Eng 2012; 40: 828-839. doi: 10.1007/s10439-011-0429-8.
117. van Beijnum JR, Dings RP, van der Linden E, Zwaans BM, Ramaekers FC, Mayo KH, Griffioen AW, Gene expression of tumor angiogenesis dissected: specific targeting of colon cancer angiogenic vasculature. Blood 2006; 108: 2339-2348. doi: 10.1182/blood-2006-02-004291.
118. Yeh WL, Lin CJ, Fu WM, Enhancement of glucose transporter expression of brain endothelial cells by vascular endothelial growth factor derived from glioma exposed to hypoxia. Mol Pharmacol 2008; 73: 170-177. doi: 10.1124/mol.107.038851.
119. Ferreira LM, Cancer metabolism: the Warburg effect today. Exp Mol Pathol 2010; 89: 372-380. doi: 10.1016/j.yexmp.2010.08.006.
120. van Horssen R, Buccione R, Willemse M, Cingir S, Wieringa B, Attanasio F, Cancer cell metabolism regulates extracellular matrix degradation by invadopodia. Eur J Cell Biol 2013; 92: 113-121. doi: 10.1016/j.ejcb.2012.11.003.
121. Metallo CM, Gameiro PA, Bell EL, Mattaini KR, Yang J, Hiller K, Jewell CM, Johnson ZR, Irvine DJ, Guarente L, Kelleher JK, Vander Heiden MG, Iliopoulos O, Stephanopoulos G, Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 2012; 481: 380-384. doi: 10.1038/nature10602.
122. Mullen AR, Wheaton WW, Jin ES, Chen PH, Sullivan LB, Cheng T, Yang Y, Linehan WM, Chandel NS, DeBerardinis RJ, Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature 2012; 481: 385-388. doi: 10.1038/nature10642.
123. Wise DR, Ward PS, Shay JE, Cross JR, Gruber JJ, Sachdeva UM, Platt JM, DeMatteo RG, Simon MC, Thompson CB, Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of α-ketoglutarate to citrate to support cell growth and viability. Proc Natl Acad Sci U S A 2011; 108: 19611-19616. doi: 10.1073/pnas.1117773108.
124. Kashiwagi S, Tsukada K, Xu L, Miyazaki J, Kozin SV, Tyrrell JA, Sessa WC, Gerweck LE, Jain RK, Fukumura D, Perivascular nitric oxide gradients normalize tumor vasculature. Nat Med 2008; 14: 255-257. doi: 10.1038/nm1730.
125. Carmeliet P, Jain RK, Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov 2011; 10: 417-427. doi: 10.1038/nrd3455.
126. Eng CH, Yu K, Lucas J, White E, Abraham RT, Ammonia derived from glutaminolysis is a diffusible regulator of autophagy. Sci Signal 2010 3 ra31. doi: 10.1126/scisignal.2000911.
127. Ko YH, Lin Z, Flomenberg N, Pestell RG, Howell A, Sotgia F, Lisanti MP, Martinez-Outschoorn UE, Glutamine fuels a vicious cycle of autophagy in the tumor stroma and oxidative mitochondrial metabolism in epithelial cancer cells: implications for preventing chemotherapy resistance. Cancer Biol Ther 2011; 12: 1085-1097. doi: 10.4161/cbt.12.12.18671.
128. Végran F, Boidot R, Michiels C, Sonveaux P, Feron O, Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-κB/IL-8 pathway that drives tumor angiogenesis. Cancer Res 2011; 71: 2550-2560. doi: 10.1158/0008-5472.CAN-10-2828.
129. Shanware NP, Bray K, Eng CH, Wang F, Follettie M, Myers J, Fantin VR, Abraham RT, Glutamine deprivation stimulates mTOR-JNK-dependent chemokine secretion. Nat Commun 2014 5 4900. doi: 10.1038/ncomms5900.
130. Lemons JM, Feng XJ, Bennett BD, Legesse-Miller A, Johnson EL, Raitman I, Pollina EA, Rabitz HA, Rabinowitz JD, Coller HA, Quiescent fibroblasts exhibit high metabolic activity. PLoS Biol 2010 8 e1000514. doi: 10.1371/journal.pbio.1000514.
131. Pavlides S, Vera I, Gandara R, Sneddon S, Pestell RG, Mercier I, Martinez-Outschoorn UE, Whitaker-Menezes D, Howell A, Sotgia F, Lisanti MP, Warburg meets autophagy: cancer-associated fibroblasts accelerate tumor growth and metastasis via oxidative stress, mitophagy, and aerobic glycolysis. Antioxid Redox Signal 2012; 16: 1264-1284. doi: 10.1089/ars.2011.4243.
132. Lisanti MP, Martinez-Outschoorn UE, Chiavarina B, Pavlides S, Whitaker-Menezes D, Tsirigos A, Witkiewicz A, Lin Z, Balliet R, Howell A, Sotgia F, Understanding the "lethal" drivers of tumor-stroma co-evolution: emerging role(s) for hypoxia, oxidative stress and autophagy/mitophagy in the tumor micro-environment. Cancer Biol Ther 2010; 10: 537-542. doi: 10.4161/cbt.10.6.13370.
133. Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, Casimiro MC, Wang C, Fortina P, Addya S, Pestell RG, Martinez-Outschoorn UE, Sotgia F, Lisanti MP, The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle 2009 8 3984 4001
134. Mockler MB, Conroy MJ, Lysaght J, Targeting T cell immunometabolism for cancer immunotherapy; understanding the impact of the tumor microenvironment. Front Oncol 2014 4 107. doi: 10.3389/fonc.2014.00107.
135. Schietinger A, Greenberg PD, Tolerance and exhaustion: defining mechanisms of T cell dysfunction. Trends Immunol 2014; 35: 51-60. doi: 10.1016/j.it.2013.10.001.
136. Parry RV, Chemnitz JM, Frauwirth KA, Lanfranco AR, Braunstein I, Kobayashi SV, Linsley PS, Thompson CB, Riley JL, CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol Cell Biol 2005; 25: 9543-9553. doi: 10.1128/MCB.25.21.9543-9553.2005.
137. Yabu M, Shime H, Hara H, Saito T, Matsumoto M, Seya T, Akazawa T, Inoue N, IL-23-dependent and -independent enhancement pathways of IL-17A production by lactic acid. Int Immunol 2011; 23: 29-41. doi: 10.1093/intimm/dxq455.
138. Galván-Peña S, O'Neill LA, Metabolic reprograming in macrophage polarization. Front Immunol 2014 5 420. doi: 10.3389/fimmu.2014.00420.
139. Mills CD, M1 and M2 Macrophages: Oracles of Health and Disease. Crit Rev Immunol 2012 32 463 488
140. Welti J, Loges S, Dimmeler S, Carmeliet P, Recent molecular discoveries in angiogenesis and antiangiogenic therapies in cancer. J Clin Invest 2013; 123: 3190-3200. doi: 10.1172/JCI70212.
141. Xu Y, An X, Guo X, Habtetsion TG, Wang Y, Xu X, Kandala S, Li Q, Li H, Zhang C, Caldwell RB, Fulton DJ, Su Y, Hoda MN, Zhou G, Wu C, Huo Y, Endothelial pfkfb3 plays a critical role in angiogenesis. Arteriosclerosis, thrombosis, and vascular biology 2014 34 1231 1239
142. Davies PF, Civelek M, Fang Y, Fleming I, The atherosusceptible endothelium: endothelial phenotypes in complex haemodynamic shear stress regions in vivo. Cardiovasc Res 2013; 99: 315-327. doi: 10.1093/cvr/cvt101.
143. Biasucci LM, Biasillo G, Stefanelli A, Inflammatory markers, cholesterol and statins: pathophysiological role and clinical importance. Clin Chem Lab Med 2010; 48: 1685-1691. doi: 10.1515/CCLM.2010.277. doi: 10.1161/ATVBAHA.113.303041.
144. Lobatto ME, Fuster V, Fayad ZA, Mulder WJ, Perspectives and opportunities for nanomedicine in the management of atherosclerosis. Nat Rev Drug Discov 2011; 10: 835-852. doi: 10.1038/nrd3578.