@article{9eeb86dc977945679b9cac04c60f632f,
title = "A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors",
abstract = "A microbially generated metabolite, PAGIn, is associated with cardiovascular disease and death in humans. Studies in animal models provide insights into PAGIn metabolism as well as its effects in driving platelet invasiveness and thrombosis through adrenergic receptors.",
keywords = "GPCR, adrenergic receptors, cardiovascular disease, gut microbe, metabolomics, thrombosis",
author = "Ina Nemet and Saha, {Prasenjit Prasad} and Nilaksh Gupta and Weifei Zhu and Romano, {Kymberleigh A.} and Skye, {Sarah M.} and Tomas Cajka and Mohan, {Maradumane L.} and Lin Li and Yuping Wu and Masanori Funabashi and Ramer-Tait, {Amanda E.} and {Naga Prasad}, {Sathyamangla Venkata} and Oliver Fiehn and Rey, {Federico E.} and Tang, {W. H.Wilson} and Fischbach, {Michael A.} and DiDonato, {Joseph A.} and Hazen, {Stanley L.}",
note = "Funding Information: This work is supported by grants from the NIH and Office of Dietary Supplements ( P01HL147823 , R01HL103866 , R01HL126827 ) and the Foundation Leducq . K.A.R. was supported in part by NIH/NHLBI training grant HL134622 . Mass spectrometry studies were performed on instrumentation housed in a facility supported in part through a Shimadzu Center of Excellence award and NIH shared instrumentation grant 1S10OD016346 . Microfluidic shear flow experiments were done with the help from the Lerner Research Institute Imaging Core . Funding Information: This work is supported by grants from the NIH and Office of Dietary Supplements (P01HL147823, R01HL103866, R01HL126827) and the Foundation Leducq. K.A.R. was supported in part by NIH/NHLBI training grant HL134622. Mass spectrometry studies were performed on instrumentation housed in a facility supported in part through a Shimadzu Center of Excellence award and NIH shared instrumentation grant 1S10OD016346. Microfluidic shear flow experiments were done with the help from the Lerner Research Institute Imaging Core. I.N. P.P.S. and N.G. designed, performed, and analyzed data from most of the studies and wrote the manuscript with input from all authors. T.C. and O.F. performed untargeted metabolic analysis; I.N. performed the mass spec analysis and compound identification; M.F. and M.A.F. performed genetic manipulation of C. sporogenes; K.A.R. helped with culturing bacteria and GF mouse experiments; and N.G. S.M.S. and W.Z. helped in the design and performance of platelet functional studies, in vivo thrombosis, and other mouse experiments. P.P.S. performed cell culturing and DMR signaling experiments. M.L.M. and S.V.N.P. helped with ADR experiments. A.E.R.-T. and F.E.R. provided GF mice. L.L. and Y.W. helped with statistical analysis. J.A.D. provided overall advice. W.H.W.T. and F.E.R. provided critical scientific input and discussions. S.L.H. conceived, designed, and supervised all studies and the drafting and editing of the manuscript. All authors contributed to the critical review of the manuscript. S.L.H. reports being named as co-inventor on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics, being a paid consultant for P&G, having received research funds from P&G and Roche Diagnostics, and being eligible to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Cleveland HeartLab, Quest Diagnostics, and P&G. The other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = mar,
day = "5",
doi = "10.1016/j.cell.2020.02.016",
language = "English (US)",
volume = "180",
pages = "862--877.e22",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",
}