skip to primary navigationskip to content
 

Dr Andrew Philip Sage Research Fellow

Dr Andrew Philip Sage, Research Fellow

Research Fellow

Immune regulation of Cardiovascular disease

Andrew Sage is accepting applications for PhD students.


Office Phone: 01223768678

Research Interests

I am investigating how different subsets of B cells regulate the development of atherosclerosis, in order to understand if immune therapies could slow or stabilise disease progression. Atherosclerosis is a complex disease with many contributing networks, including vessel wall inflammation, metabolism and the recruitment and activation of innate and adaptive immune systems.

Contrary to long-standing views, not all B cells play a protective, anti-atherogenic role. The identification of the diversity of B cell subsets and B cell functions means there may be multiple, potentially antagonistic, pathways by which B cells are involved in plaque development. Therefore, we are interrogating the mechanisms of B cell action and the subtypes of B cells that may be involved. We are also interested in how the BAFF family of ligands and receptors are involved in cardiovascular disease. We believe this research could lead to modification of current treatments used in other diseases to treat heart disease and stroke, may reveal novel pathways promoting atherosclerosis that could be targeted by new treatments and aid in understanding the links between autoimmune diseases and cardiovascular risk.

External Collaborators - Prof. Christopher Binder (Vienna, Austria) and Dr Pasquale Maffia (Glasgow, UK)

Keywords

B cells ; immune tolerance ; MHC class II ; autoantibody ; IgG ; Fc gamma receptors ; adaptive immunity ; antigen presentation ; dendritic cells

Topics

  • atherosclerosis
  • Immunology
  • autoimmunity
  • immune response in cardiovascular disease

Key Publications

Sage AP, Nus M, Bagchi Chakraborty J, Tsiantoulas D, Newland SA, Finigan AJ, Masters L, Binder CJ, Mallat Z. (2017) X-box Binding Protein-1 dependent Plasma Cell Responses Limit the Development of Atherosclerosis. Circ Res. 121:270-281. doi:             10.1161/CIRCRESAHA.117.310884

Newland SA, Mohanta S, Clément M, Taleb S, Walker JA, Nus M, Sage AP, Yin C, Hu D, Kitt LL, Finigan AJ, Rodewald HR, Binder CJ, McKenzie ANJ, Habenicht AJ, Mallat Z. (2017) Type-2 innate lymphoid cells control the development of atherosclerosis in mice. Nat Commun. 8:15781. doi: 10.1038/ncomms15781.

Sage AP and Mallat Z. (2017) Readapting the adaptive immune system – Therapeutic approaches for atherosclerosis. Review. Br J Pharmacol. doi: 10.1111/bph.13700.

Nus M, Sage AP, Lu Y, Masters L, Lam BYH, Newland SA, Weller S, Tsiantoulas D, Raffort J, Marcus D, Finigan A, Kitt L, Figg N, Schirmbeck R, Kneilling M, Yeo GSH, Binder CJ, de la Pompa JL, Mallat Z. (2017) Marginal zone B cells control follicular helper T cell response to high cholesterol diet. Nat Med. 23(5):601-610. doi: 10.1038/nm.4315.

Tsiantoulas D, Sage AP, Mallat Z and Binder C (2015). Targeting B cells in atherosclerosis: closing the gap from bench to bedside. Review. ATVB. 35(2):296-302. doi: 10.1161/ATVBAHA.114.303569

Sage AP, Murphy D, Sabir S, Grazia G, Maffia P, Masters L, Baker L, Finigan A, Harrison J, Ludewig B, Reith W, Hansson G, Reizis B, Hugues S, Mallat Z. (2014) MHC class II-restricted antigen presentation by plasmacytoid dendritic cells drives pro-atherogenic immunity. Circulation. 130(16):1363-73. doi: 10.1161/CIRCULATIONAHA.114.011090.

Zouggari Y, Ait-Oufella H, Bonnin P, Simon T, Sage AP, Guérin C, Vilar J, Caligiuri G, Tsiantoulas D, Laurans L, Dumeau E, Kotti S, Bruneval P, Charo I, Binder C, Danchin N, Tedgui A, Tedder T, Silvestre J-S, Mallat Z. (2013). B lymphocytes trigger Ccl7-dependent mobilization of monocytes and promote adverse ventricular remodeling after acute myocardial infarction. Nat Med. 19(10):1273-80. doi: 10.1038/nm.3284.

Sage AP, Tsiantoulas D, Baker L, Harrison J, Masters L, Murphy D, Mallat Z. (2012). BAFF receptor deficiency reduces the development of atherosclerosis in mice. Arterioscler Thromb Vasc Biol, 32(7), 1573-1576. doi: 10.1161/ATVBAHA.111.244731.

Other Publications

Richardson, Sage AP et al. Telomerase mediates lymphocyte proliferation but not the atherosclerosis-suppressive potential of regulatory T-cells (2018). ATVB. doi.org/10.1161/ATVBAHA.117.309940

De Riva A, Wallberg M, Ronchi F, Coulson R, Sage AP, Thorne L, Goodfellow I, McCoy KD, Azuma M, Cooke A, Busch R. (2017) Regulation of type 1 diabetes development and B-cell activation in nonobese diabetic mice by early life exposure to a diabetogenic environment. PLoS One. doi.org/10.1371/journal.pone.0181964.

Ait-Oufella, H and Sage, AP. (2016) The Sunlight, a new immunomodulatory approach of atherosclerosis. ATVB. 37(1):7-9. doi: 10.1161/ATVBAHA.116.308637. Commentary.

Sage AP. Calcioprotein particles: the LDL of vascular calcification? (2016) Atherosclerosis. 251:516-517. doi: 10.1016/j.atherosclerosis.2016.06.032. Commentary.

Sage AP, Nus M, Murphy D, Finigan A, Baker L, Masters L and Mallat Z. (2015) Regulatory B cell specific interleukin-10 does not regulate atherosclerosis in mice. ATVB. 35(8):1770-3.

Ackers-Johnson M*, Talasila A*, Long X, Sage AP, Bot I, Morrell N, Bennett MR, Miano Jand Sinha S. (2015). Myocardin Regulates Vascular Smooth Muscle Cell Inflammatory Activation and Disease. ATVB, 35(4):817-28. doi: 10.1161/ATVBAHA.114.305218.

Loinard C, Basatemur G, Masters L, Baker L, Harrison J, Finigan A, Figg, Vilar J, Sage AP, Mallat Z. (2014) Deletion of 9p21 non-coding cardiovascular risk interval in mice promotes vascular aneurysm. Circ Cardio Gen 7(6):799-805. doi: 10.1161/CIRCGENETICS.114.000696.

Ait-Oufella H, Sage AP, Mallat Z, Tedgui A. (2014). Adaptive (T and B cells) immunity and control by dendritic cells in atherosclerosis. Circ Res, 114(10), 1640-1660. doi:10.1161/CIRCRESAHA.114.302761

Sage AP & Mallat Z. (2014). Multiple potential roles for B cells in atherosclerosis. Ann Med. doi:10.3109/07853890.2014.900272

Sage AP & Mallat Z. (2014). Sialyltransferase activity and atherosclerosis. Circ Res. 114(6):935-7. doi: 10.1161/CIRCRESAHA.114.303480.

Morony S, Sage AP, Corbin T, Lu J, Tintut Y, Demer LL. (2012) Enhanced mineralization potential of vascular cells from SM22α‐RANKL-TG mice. Cal Tissue Int. 91(6):379-86. doi: 10.1007/s00223-012-9655-9

Cheng H, Reddy A, Sage AP, Lu J, Garfinkel A, Tintut Y, Demer LL. (2012). Focal high cell density generates a gradient of patterns in self-organizing vascular mesenchymal cells. J Vasc Res, 49(5), 441-446. doi:10.1159/000339568

Sage AP, Lu J, Atti E, Tetradis S, Ascenzi MG, Adams DJ, Demer LL, Tintut Y. (2011). Hyperlipidemia induces resistance to PTH bone anabolism in mice via oxidized lipids. J Bone Miner Res, 26(6), 1197-1206. doi:10.1002/jbmr.312

Sage AP, Lu J, Tintut Y, Demer LL. (2011). Hyperphosphatemia-induced nanocrystals upregulate the expression of bone morphogenetic protein-2 and osteopontin genes in mouse smooth muscle cells in vitro. Kidney Int, 79(4), 414-422. doi:10.1038/ki.2010.390

Sage AP, Tintut Y, Demer LL. (2010). Regulatory mechanisms in vascular calcification. Nat Rev Cardiol, 7(9), 528-536. doi:10.1038/nrcardio.2010.115

Tseng W, Lu J, Bishop GA, Watson AD, Sage AP, Demer LL, Tintut Y. (2010). Regulation of interleukin-6 expression in osteoblasts by oxidized phospholipids. J Lipid Res, 51(5), 1010-1016. doi:10.1194/jlr.M001099

Sage A, Tintut Y, Garfinkel A, Demer LL. (2009). Systems biology of vascular calcification. Trends Cardiovasc Med, 19(4), 118-123. doi:10.1016/j.tcm.2009.07.002

Hsu JJ, Lu J, Huang MS, Geng Y, Sage AP, Bradley MN, Tintut Y. (2009). T0901317, an LXR agonist, augments PKA-induced vascular cell calcification. FEBS Lett, 583(8), 1344-1348. doi:10.1016/j.febslet.2009.03.039

Alam MU, Kirton JP, Wilkinson FL, Towers E, Sinha S, Rouhi M, Vizard TN, Sage AP, Martin D, Ward DT, Alexander MY, Riccardi D, Canfield, A. E. (2009). Calcification is associated with loss of functional calcium-sensing receptor in vascular smooth muscle cells. Cardiovasc Res, 81(2), 260-268. doi:10.1093/cvr/cvn279

Demer LL, Sage AP, Tintut Y. (2008). Nanoscale architecture in atherosclerotic calcification. Arterioscler Thromb Vasc Biol, 28(11), 1882-1884. doi:10.1161/ATVBAHA.108.175711

Huang MS, Lu J, Ivanov Y, Sage AP, Tseng W, Demer LL, Tintut Y. (2008). Hyperlipidemia impairs osteoanabolic effects of PTH. J Bone Miner Res, 23(10), 1672-1679. doi:10.1359/jbmr.080513

Huang MS, Sage AP, Lu J, Demer LL, Tintut Y. (2008). Phosphate and pyrophosphate mediate PKA-induced vascular cell calcification. Biochem Biophys Res Commun, 374(3), 553-558. doi:10.1016/j.bbrc.2008.07.062

Collett GD*, Sage AP*, Kirton JP, Alexander MY, Gilmore AP, Canfield AE. (2007). *Co first author. Axl/phosphatidylinositol 3-kinase signaling inhibits mineral deposition by vascular smooth muscle cells. Circ Res, 100(4), 502-509. doi:10.1161/01.RES.0000258854.03388.02