S1P receptor 1-Mediated Anti-Renin-Angiotensin System Cardioprotection: Pivotal Role of Mast Cell Aldehyde Dehydrogenase Type 2

The Journal of Pharmacology and Experimental Therapeutics
Alice MarinoRoberto Levi

Abstract

In the ischemic-reperfused (I/R) heart, renin-containing mast cells (MC) release enzymatically active renin, activating a local renin-angiotensin system (RAS), causing excessive norepinephrine release and arrhythmic dysfunction. Activation of Gi-receptors on MC and/or ischemic preconditioning (IPC) prevent renin release, thus providing anti-RAS cardioprotection. We questioned whether sphingosine-1-phosphate (S1P), a sphingolipid produced in the I/R heart, might afford anti-RAS cardioprotection by activating Gi-coupled S1P1 receptors (S1P1R) on MC. We report that activation of Gi-coupled S1P1R in cardiac MC confers IPC-like anti-RAS cardioprotection due to S1P1R-mediated inhibition of I/R-induced cardiac MC degranulation and renin release. This results from an initial translocation of protein kinase C subtype-ε and subsequent activation of aldehyde dehydrogenase type 2 (ALDH2), culminating in the elimination of the MC-degranulating effects of acetaldehyde and other toxic species produced during I/R. Inhibition of toxic aldehydes-induced MC-renin release prevents local RAS activation, reduces infarct size, and alleviates arrhythmias. Notably, these cardioprotective effects are lacking in hearts and MC from gene-targeted knock-in ...Continue Reading

References

Jul 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·L A Greene, A S Tischler
Jan 1, 1991·Free Radical Biology & Medicine·H EsterbauerH Zollner
Oct 4, 1996·The Journal of Biological Chemistry·J A JohnsonD Mochly-Rosen
Sep 28, 1998·Biochimica Et Biophysica Acta·H KanekoM Inoue
Jun 25, 1999·Free Radical Biology & Medicine·T A ZainalT D Oberley
Sep 10, 1999·Annals of Medicine·K E Airaksinen
Aug 6, 2003·The Journal of Comparative Neurology·Tania VitalisOlivier Cases
Sep 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Randi B SilverRoberto Levi
Sep 7, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Luping GuoGavin E Arteel
Sep 29, 2004·Circulation·Zhu-Qiu JinJoel S Karliner
Apr 26, 2006·Cardiovascular Research·Koichi InagakiDaria Mochly-Rosen
Jul 25, 2006·European Journal of Pharmacology·Naoto AdachiTatsuru Arai
Jul 28, 2006·American Journal of Physiology. Cell Physiology·Puja K Mehta, Kathy K Griendling
May 15, 2007·Immunological Reviews·Alicia C ReidRoberto Levi
Jan 8, 2008·Blood·Carole A OskeritzianSarah Spiegel
Jan 19, 2008·Proceedings of the National Academy of Sciences of the United States of America·Arul VeerappanRandi B Silver
Jun 17, 2008·Pharmacological Reviews·Kazuaki TakabeSarah Spiegel
Aug 19, 2008·Molecular Pharmacology·Pedro J Gonzalez-CabreraHugh Rosen
Sep 13, 2008·Science·Che-Hong ChenDaria Mochly-Rosen
Mar 14, 2009·Cardiovascular Research·Christopher K Means, Joan Heller Brown
Aug 4, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Donald A VesseyJoel S Karliner
Sep 18, 2009·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Shuzhen ChenYanfang Chen
Dec 17, 2009·Trends in Cardiovascular Medicine·Grant R BudasDaria Mochly-Rosen
Sep 28, 2010·Biochimica Et Biophysica Acta·Nina KaludercicNazareno Paolocci
Aug 2, 2011·Seminars in Immunopathology·Hideru Obinata, Timothy Hla
Apr 16, 2013·Antioxidants & Redox Signaling·Nina KaludercicNazareno Paolocci
Oct 8, 2013·Handbook of Clinical Neurology·Alex Y Tan, Richard L Verrier
Nov 23, 2013·The American Journal of Pathology·Silvia AldiRoberto Levi
Aug 23, 2012·World Journal of Hypertension·Hairuo WenLai-Hua Xie

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Citations

Mar 3, 2019·Cardiovascular Research·Ioanna AndreadouDerek J Hausenloy
Jun 17, 2018·The Journal of Pharmacology and Experimental Therapeutics·Alice MarinoRoberto Levi
Sep 10, 2019·Alcoholism, Clinical and Experimental Research·Jie XiongQing Su
Dec 15, 2017·International Journal of Molecular Sciences·Ernestina M De FrancescoMarcello Maggiolini
Dec 15, 2019·International Journal of Molecular Sciences·Do-Kyun KimAna Olivera
Jul 25, 2019·Frontiers in Cellular Neuroscience·Gilda VarricchiGiuseppe Spadaro
Feb 15, 2019·Frontiers in Immunology·Jun-Yan XuYue-Jin Yang
Aug 22, 2020·Journal of Lipid and Atherosclerosis·Anna Kovilakath, L Ashley Cowart
Nov 5, 2019·Frontiers in Immunology·Ethan StrattanGerhard C Hildebrandt
Apr 30, 2021·Chemical Research in Toxicology·Ki H MaGary A Rockwood
Mar 20, 2021·International Angiology : a Journal of the International Union of Angiology·Raimondo FeminòEmidio Troiani
May 18, 2021·Frontiers in Cardiovascular Medicine·Niek J PluijmertPaul H A Quax

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