Inhibition of endothelial notch signaling impairs fatty acid transport and leads to metabolic and vascular remodeling of the adult heart

Circulation

Volumn 137, Issue 24, 2018, Pages 2592-2608

  Jabs, Markus ^a   Rose, Adam J ^c,d   Lehmann, Lorenz H ^c,e   Taylor, Jacqueline ^a   Moll, Iris ^a   Sijmonsma, Tjeerd P ^c   Herberich, Stefanie E ^a   Sauer, Sven W ^c   Poschet, Gernot ^f   Federico, Giuseppina ^b   Mogler, Carolin ^g   Weis, Eva Maria ^a   Augustin, Hellmut G ^b   Yan, Minhong ^i,j   Gretz, Norbert ^f   Schmid, Roland M ^h   Adams, Ralf H ^k   Gröne, Hermann Joseph ^b,f   Hell, Rüdiger ^f   Okun, Jürgen G ^c   Backs, Johannes ^c,e   Nawroth, Peter P ^c   Herzig, Stephan ^l   Fischer, Andreas ^a,c,f   more..

^a GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^b German Cancer Research Center   (United States)

^c UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^d MONASH UNIVERSITY   (Australia)

^e Center for Cardiovascular Research   (United States)

^f UNIVERSITY OF HEIDELBERG   (Germany)

^g Institute for Pathology   (United States)

^h TECHNICAL UNIVERSITY OF MUNICH   (Germany)

ⁱ TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^j GENENTECH INC   (United States)

^k UNIVERSITY OF MÜNSTER   (Germany)

^l INSTITUTE OF EPIDEMIOLOGY   (Germany)

more..

Author keywords

angiogenesis; animal model cardiovascular disease; endothelial cell; metabolism

Indexed keywords

ANGIOPOIETIN; ANGPT4 PROTEIN, MOUSE; CD36 ANTIGEN; CD36 PROTEIN, MOUSE; DLL4 PROTEIN, MOUSE; FABP4 PROTEIN, MOUSE; FATTY ACID; FATTY ACID BINDING PROTEIN; GLUCOSE; MEMBRANE PROTEIN; MTOR PROTEIN, MOUSE; NOTCH RECEPTOR; S6 KINASE; SIGNAL PEPTIDE; TARGET OF RAPAMYCIN KINASE;

ANGIOGENESIS; ANIMAL; CARDIAC MUSCLE; CARDIAC MUSCLE CELL; CYTOLOGY; GENETICS; METABOLISM; MOUSE; SIGNAL TRANSDUCTION; TRANSGENIC MOUSE; VASCULAR ENDOTHELIUM; VASCULAR REMODELING;

ANGIOPOIETINS; ANIMALS; CD36 ANTIGENS; ENDOTHELIUM, VASCULAR; FATTY ACID-BINDING PROTEINS; FATTY ACIDS; GLUCOSE; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MEMBRANE PROTEINS; MICE; MICE, TRANSGENIC; MYOCARDIUM; MYOCYTES, CARDIAC; NEOVASCULARIZATION, PHYSIOLOGIC; RECEPTORS, NOTCH; RIBOSOMAL PROTEIN S6 KINASES; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; VASCULAR REMODELING;

EID: 85050211112     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.117.029733     Document Type: Article

References (46)

1. Augustin HG, Koh GY. Organotypic vasculature: from descriptive heterogeneity to functional pathophysiology. Science. 2017;357:eaal2379. doi:10.1126/science.aal2379.
2. Ramasamy SK, Kusumbe AP, Adams RH. Regulation of tissue morphogenesis by endothelial cell-derived signals. Trends Cell Biol. 2015;25:148-157. doi: 10.1016/j.tcb.2014.11.007.
3. Coppiello G, Collantes M, Sirerol-Piquer MS, Vandenwijngaert S, Schoors S, Swinnen M, Vandersmissen I, Herijgers P, Topal B, van Loon J, Goffin J, Prósper F, Carmeliet P, García-Verdugo JM, Janssens S, Peñuelas I, Aranguren XL, Luttun A. Meox2/Tcf15 heterodimers program the heart capillary endothelium for cardiac fatty acid uptake. Circulation. 2015;131:815-826. doi: 10.1161/CIRCULATIONAHA.114.013721.
4. Kanda T, Brown JD, Orasanu G, Vogel S, Gonzalez FJ, Sartoretto J, Michel T, Plutzky J. PPARgamma in the endothelium regulates metabolic responses to high-fat diet in mice. J Clin Invest. 2009;119:110-124. doi: 10.1172/JCI36233.
5. Dijkstra MH, Pirinen E, Huusko J, Kivelä R, Schenkwein D, Alitalo K, Ylä-Herttuala S. Lack of cardiac and high-fat diet induced metabolic phenotypes in two independent strains of Vegf-b knockout mice. Sci Rep. 2014;4:6238. doi: 10.1038/srep06238.
6. Hagberg CE, Falkevall A, Wang X, Larsson E, Huusko J, Nilsson I, van Meeteren LA, Samen E, Lu L, Vanwildemeersch M, Klar J, Genove G, Pietras K, Stone-Elander S, Claesson-Welsh L, Ylä-Herttuala S, Lindahl P, Eriksson U. Vascular endothelial growth factor B controls endothelial fatty acid uptake. Nature. 2010;464:917-921. doi: 10.1038/nature08945.
7. Kivelä R, Bry M, Robciuc MR, Räsänen M, Taavitsainen M, Silvola JM, Saraste A, Hulmi JJ, Anisimov A, Mäyränpää MI, Lindeman JH, Eklund L, Hellberg S, Hlushchuk R, Zhuang ZW, Simons M, Djonov V, Knuuti J, Mervaala E, Alitalo K. 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.
8. Bi P, Shan T, Liu W, Yue F, Yang X, Liang XR, Wang J, Li J, Carlesso N, Liu X, Kuang S. Inhibition of Notch signaling promotes browning of white adipose tissue and ameliorates obesity. Nat Med. 2014;20:911-918. doi: 10.1038/nm.3615.
9. Gao F, Yao M, Shi Y, Hao J, Ren Y, Liu Q, Wang X, Duan H. Notch pathway is involved in high glucose-induced apoptosis in podocytes via Bcl-2 and p53 pathways. J Cell Biochem. 2013;114:1029-1038. doi: 10.1002/jcb.24442.
10. Pajvani UB, Qiang L, Kangsamaksin T, Kitajewski J, Ginsberg HN, Accili D. Inhibition of Notch uncouples Akt activation from hepatic lipid accumulation by decreasing mTorc1 stability. Nat Med. 2013;19:1054-1060. doi: 10.1038/nm.3259.
11. Pajvani UB, Shawber CJ, Samuel VT, Birkenfeld AL, Shulman GI, Kitajewski J, Accili D. Inhibition of Notch signaling ameliorates insulin resistance in a FoxO1-dependent manner. Nat Med. 2011;17:961-967. doi: 10.1038/nm.2378.
12. Briot A, Civelek M, Seki A, Hoi K, Mack JJ, Lee SD, Kim J, Hong C, Yu J, Fishbein GA, Vakili L, Fogelman AM, Fishbein MC, Lusis AJ, Tontonoz P, Navab M, Berliner JA, Iruela-Arispe ML. Endothelial NOTCH1 is suppressed by circulating lipids and antagonizes inflammation during atherosclerosis. J Exp Med. 2015;212:2147-2163. doi: 10.1084/jem.20150603.
13. 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.
14. Chiorean EG, LoRusso P, Strother RM, Diamond JR, Younger A, Messersmith WA, Adriaens L, Liu L, Kao RJ, DiCioccio AT, Kostic A, Leek R, Harris A, Jimeno A. A phase I first-in-human study of enoticumab (REGN421), a fully human delta-like ligand 4 (Dll4) monoclonal antibody in patients with advanced solid tumors. Clin Cancer Res. 2015;21:2695-2703. doi: 10.1158/1078-0432.CCR-14-2797.
15. Smith DC, Eisenberg PD, Manikhas G, Chugh R, Gubens MA, Stagg RJ, Kapoun AM, Xu L, Dupont J, Sikic B. A phase I dose escalation and expansion study of the anticancer stem cell agent demcizumab (anti-DLL4) in patients with previously treated solid tumors. Clin Cancer Res. 2014;20:6295-6303. doi: 10.1158/1078-0432.CCR-14-1373.
16. Ramasamy SK, Kusumbe AP, Wang L, Adams RH. Endothelial Notch activity promotes angiogenesis and osteogenesis in bone. Nature. 2014;507:376-380. doi: 10.1038/nature13146.
17. Barber ED, Lands WE. Determination of acyl-CoA concentrations using pancreatic lipase. Biochim Biophys Acta. 1971;250:361-366.
18. Golovko MY, Murphy EJ. An improved method for tissue long-chain acyl-CoA extraction and analysis. J Lipid Res. 2004;45:1777-1782. doi: 10.1194/jlr.D400004-JLR200.
19. Lehmann LH, Rostosky JS, Buss SJ, Kreusser MM, Krebs J, Mier W, Enseleit F, Spiger K, Hardt SE, Wieland T, Haass M, Lüscher TF, Schneider MD, Parlato R, Gröne HJ, Haberkorn U, Yanagisawa M, Katus HA, Backs J. Essential role of sympathetic endothelin A receptors for adverse cardiac remodeling. Proc Natl Acad Sci U S A. 2014;111:13499-13504. doi: 10.1073/pnas.1409026111.
20. Furler SM, Cooney GJ, Hegarty BD, Lim-Fraser MY, Kraegen EW, Oakes ND. Local factors modulate tissue-specific NEFA utilization: assessment in rats using 3H-®-2-bromopalmitate. Diabetes. 2000;49:1427-1433.
21. Ridgway J, Zhang G, Wu Y, Stawicki S, Liang WC, Chanthery Y, Kowalski J, Watts RJ, Callahan C, Kasman I, Singh M, Chien M, Tan C, Hongo JA, de Sauvage F, Plowman G, Yan M. Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis. Nature. 2006;444:1083-1087. doi: 10.1038/nature05313.
22. Hofmann JJ, Iruela-Arispe ML. Notch signaling in blood vessels: who is talking to whom about what? Circ Res. 2007;100:1556-1568. doi: 10.1161/01.RES.0000266408.42939.e4.
23. Wieland E, Rodriguez-Vita J, Liebler SS, Mogler C, Moll I, Herberich SE, Espinet E, Herpel E, Menuchin A, Chang-Claude J, Hoffmeister M, Gebhardt C, Brenner H, Trumpp A, Siebel CW, Hecker M, Utikal J, Sprinzak D, Fischer A. Endothelial Notch1 activity facilitates metastasis. Cancer Cell. 2017;31:355-367. doi: 10.1016/j.ccell.2017.01.007.
24. Szabadkai G, Duchen MR. Mitochondria: the hub of cellular Ca2+ signaling. Physiology (Bethesda). 2008;23:84-94. doi: 10.1152/physiol.00046.2007.
25. Luo M, Anderson ME. Mechanisms of altered Ca2sup+/sup handling in heart failure. Circ Res. 2013;113:690-708. doi: 10.1161/CIRCRESAHA.113.301651.
26. Taegtmeyer H, Sen S, Vela D. Return to the fetal gene program: a suggested metabolic link to gene expression in the heart. Ann N Y Acad Sci. 2010;1188:191-198. doi: 10.1111/j.1749-6632.2009.05100.x.
27. Kundu BK, Zhong M, Sen S, Davogustto G, Keller SR, Taegtmeyer H. Remodeling of glucose metabolism precedes pressure overload-induced left ventricular hypertrophy: review of a hypothesis. Cardiology. 2015;130:211-220. doi: 10.1159/000369782.
28. Davies BS, Beigneux AP, Barnes RH 2nd, 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. O'Brien KD, Ferguson M, Gordon D, Deeb SS, Chait A. Lipoprotein lipase is produced by cardiac myocytes rather than interstitial cells in human myocardium. Arterioscler Thromb. 1994;14:1445-1451.
30. Goto K, Iso T, Hanaoka H, Yamaguchi A, Suga T, Hattori A, Irie Y, Shinagawa Y, Matsui H, Syamsunarno MR, Matsui M, Haque A, Arai M, Kunimoto F, Yokoyama T, Endo K, Gonzalez FJ, Kurabayashi M. Peroxisome proliferator-activated receptor-γ in capillary endothelia promotes fatty acid uptake by heart during long-term fasting. J Am Heart Assoc. 2013;2:e004861. doi: 10.1161/JAHA.112.004861.
31. Harjes U, Bridges E, McIntyre A, Fielding BA, Harris AL. Fatty acid-binding protein 4, a point of convergence for angiogenic and metabolic signaling pathways in endothelial cells. J Biol Chem. 2014;289:23168-23176. doi: 10.1074/jbc.M114.576512.
32. Gallagher D, Belmonte D, Deurenberg P, Wang Z, Krasnow N, Pi-Sunyer FX, Heymsfield SB. Organ-tissue mass measurement allows modeling of REE and metabolically active tissue mass. Am J Physiol. 1998;275(2 pt 1):E249-E258.
33. Buller CL, Heilig CW, Brosius FC III. GLUT1 enhances mTOR activity independently of TSC2 and AMPK. Am J Physiol Renal Physiol. 2011;301:F588-F596. doi: 10.1152/ajprenal.00472.2010.
34. Kolwicz SC Jr, Purohit S, Tian R. Cardiac metabolism and its interactions with contraction, growth, and survival of cardiomyocytes. Circ Res. 2013;113:603-616. doi: 10.1161/CIRCRESAHA.113.302095.
35. Sciarretta S, Volpe M, Sadoshima J. Mammalian target of rapamycin signaling in cardiac physiology and disease. Circ Res. 2014;114:549-564. doi: 10.1161/CIRCRESAHA.114.302022.
36. Wende AR, O'Neill BT, Bugger H, Riehle C, Tuinei J, Buchanan J, Tsushima K, Wang L, Caro P, Guo A, Sloan C, Kim BJ, Wang X, Pereira RO, McCrory MA, Nye BG, Benavides GA, Darley-Usmar VM, Shioi T, Weimer BC, Abel ED. Enhanced cardiac Akt/protein kinase B signaling contributes to pathological cardiac hypertrophy in part by impairing mitochondrial function via transcriptional repression of mitochondrion-targeted nuclear genes. Mol Cell Biol. 2015;35:831-846. doi:10.1128/MCB.01109-14.
37. McMullen JR, Sherwood MC, Tarnavski O, Zhang L, Dorfman AL, Shioi T, Izumo S. Inhibition of mTOR signaling with rapamycin regresses established cardiac hypertrophy induced by pressure overload. Circulation. 2004;109:3050-3055. doi: 10.1161/01.CIR.0000130641.08705.45.
38. Shioi T, McMullen JR, Tarnavski O, Converso K, Sherwood MC, Manning WJ, Izumo S. Rapamycin attenuates load-induced cardiac hypertrophy in mice. Circulation. 2003;107:1664-1670. doi: 10.1161/01.CIR.0000057979.36322.88.
39. Song NJ, Yun UJ, Yang S, Wu C, Seo CR, Gwon AR, Baik SH, Choi Y, Choi BY, Bahn G, Kim S, Kwon SM, Park JS, Baek SH, Park TJ, Yoon K, Kim BJ, Mattson MP, Lee SJ, Jo DG, Park KW. Notch1 deficiency decreases hepatic lipid accumulation by induction of fatty acid oxidation. Sci Rep. 2016;6:19377. doi: 10.1038/srep19377.
40. Liu Z, Turkoz A, Jackson EN, Corbo JC, Engelbach JA, Garbow JR, Piwnica-Worms DR, Kopan R. Notch1 loss of heterozygosity causes vascular tumors and lethal hemorrhage in mice. J Clin Invest. 2011;121:800-808. doi: 10.1172/JCI43114.
41. Nielsen CM, Cuervo H, Ding VW, Kong Y, Huang EJ, Wang RA. Deletion of Rbpj from postnatal endothelium leads to abnormal arteriovenous shunting in mice. Development. 2014;141:3782-3792. doi: 10.1242/dev.108951.
42. Yan M, Callahan CA, Beyer JC, Allamneni KP, Zhang G, Ridgway JB, Niessen K, Plowman GD. Chronic DLL4 blockade induces vascular neoplasms. Nature. 2010;463:E6-E7. doi: 10.1038/nature08751.
43. Chi X, Shetty SK, Shows HW, Hjelmaas AJ, Malcolm EK, Davies BS. Angiopoietin-like 4 modifies the interactions between lipoprotein lipase and its endothelial cell transporter GPIHBP1. J Biol Chem. 2015;290:11865-11877. doi: 10.1074/jbc.M114.623769.
44. Yu X, Burgess SC, Ge H, Wong KK, Nassem RH, Garry DJ, Sherry AD, Malloy CR, Berger JP, Li C. Inhibition of cardiac lipoprotein utilization by transgenic overexpression of Angptl4 in the heart. Proc Natl Acad Sci U S A. 2005;102:1767-1772. doi: 10.1073/pnas. 0409564102.
45. Nakajima H, Ishida T, Satomi-Kobayashi S, Mori K, Hara T, Sasaki N, Yasuda T, Toh R, Tanaka H, Kawai H, Hirata K. Endothelial lipase modulates pressure overload-induced heart failure through alternative pathway for fatty acid uptake. Hypertension. 2013;61:1002-1007. doi: 10.1161/HYPERTENSIONAHA.111.201608.
46. Iso T, Maeda K, Hanaoka H, Suga T, Goto K, Syamsunarno MR, Hishiki T, Nagahata Y, Matsui H, Arai M, Yamaguchi A, Abumrad NA, Sano M, Suematsu M, Endo K, Hotamisligil GS, Kurabayashi M. 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.