Inflammation and Atherosclerosis
The links between the major theme of the Libby laboratory, inflammation in cardiovascular diseases, to metabolic diseases including diabetes and obesity have become increasingly apparent. Work from Libby laboratory has explored the interface between adipose tissue, adaptive immunity, and atherosclerosis. We showed that T cells regulate aspects of biology of adipose tissue, defined a role for the Th1 cytokine gamma interferon in regulating insulin sensitivity in obese mice, and in new studies have explored the mechanisms of T cell recruitment to adipose tissue. We have also explored the interface between adiponectin and aspects of the immune and inflammatory response related to atherothrombosis. These studies can benefit from the use of proteomic and RNA profiling facilities available through BADERC. Dr. Libby as a true translational investigator contributed to the study that first demonstrated the link between statin treatment and incident diabetes, and explored the risk factors for this relationship. Dr. Libby has moreover co-led the conception and execution of a large-scale cardiovascular outcome trial (CANTOS) that targets interleukin-1 beta that has prespecified incident diabetes as a secondary endpoint.
1. Leuschner F, Dutta P, Gorbatov R, Novobrantseva TI, Donahoe JS, Courties G, Lee KM, Kim JI, Markmann JF, Marinelli B, Panizzi P, Lee WW, Iwamoto Y, Milstein S, Epstein-Barash H, Cantley W, Wong J, Cortez-Retamozo V, Newton A, Love K, Libby P, Pittet MJ, Swirski FK, Koteliansky V, Langer R, Weissleder R, Anderson DG, Nahrendorf M.Therapeutic siRNA silencing in inflammatory monocytes in mice. Nat Biotechnol. 2011 Oct 9;29(11):1005-10. PMCID: PMC3212614
2. Libby P. Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol. 2012; 32(9): 2045–2051. PMCID: PMC3422754.
3. Cheng X, Folco EJ, Shimizu K, Libby P.Adiponectin induces pro-inflammatory programs in human macrophages and CD4+ T cells. J Biol Chem. 2012; 287: 36896–36904. PMCID: PMC3481292
4. Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012 August 11; 380(9841): 565–571. PMCID: PMC3774022
5. Dutta P, Courties G, Wei Y, Leuschner F, Gorbatov R, Robbins CS, Iwamoto Y, Thompson B, Carlson AL, Heidt T, Majmudar MD, Lasitschka F, Etzrodt M, Waterman P, Waring MT, Chicoine AT, van der Laan AM, Niessen HW, Piek JJ, Rubin BB, Butany J, Stone JR, Katus HA, Murphy SA, Morrow DA, Sabatine MS, Vinegoni C, Moskowitz MA, Pittet MJ, Libby P, Lin CP, Swirski FK, Weissleder R, Nahrendorf M. Myocardial infarction accelerates atherosclerosis. Nature. 2012 Jul 19;487(7407):325-9. PMCID: PMC3401326.
6. Robbins CS, Hilgendorf I, Weber GF, Theurl I, Iwamoto Y, Figueiredo JL, Gorbatov R, Sukhova GK, Gerhardt LM, Smyth D, Zavitz CC, Shikatani EA, Parsons M, van Rooijen N, Lin HY, Husain M, Libby P, Nahrendorf M, Weissleder R, Swirski FK. Local proliferation dominates lesional macrophage accumulation in atherosclerosis. Nat Med. 2013;19(9):1166-72. PMCID: PMC3769444
7. Okamoto Y, Ishii S, Croce K, Katsumata H, Fukushima M, Kihara S, Libby P, Minami S.Adiponectin inhibits macrophage tissue factor, a key trigger of thrombosis in disrupted atherosclerotic plaques. Atherosclerosis. 2013; 226(2): 373–377. Correction in: volume 227 on page 449. PMCID: PMC3580852