Lysophosphatidic acid acts on LPA1 receptor to increase H2 O2 during flow-induced dilation in human adipose arterioles

British Journal of Pharmacology
Dawid S ChabowskiDavid D Gutterman

Abstract

NO produces arteriolar flow-induced dilation (FID) in healthy subjects but is replaced by mitochondria-derived hydrogen peroxide (mtH2 O2 ) in patients with coronary artery disease (CAD). Lysophosphatidic acid (LPA) is elevated in patients with risk factors for CAD, but its functional effect in arterioles is unknown. We tested whether elevated LPA changes the mediator of FID from NO to mtH2 O2 in human visceral and subcutaneous adipose arterioles. Arterioles were cannulated on glass micropipettes and pressurized to 60 mmHg. We recorded lumen diameter after graded increases in flow in the presence of either NOS inhibition (L-NAME) or H2 O2 scavenging (Peg-Cat) ± LPA (10 μM, 30 min), ±LPA1 /LPA3 receptor antagonist (Ki16425) or LPA2 receptor antagonist (H2L5186303). We analysed LPA receptor RNA and protein levels in human arterioles and human cultured endothelial cells. FID was inhibited by L-NAME but not Peg-Cat in untreated vessels. In vessels treated with LPA, FID was of similar magnitude but inhibited by Peg-Cat while L-NAME had no effect. Rotenone attenuated FID in vessels treated with LPA indicating mitochondria as a source of ROS. RNA transcripts from LPA1 and LPA2 but not LPA3 receptors were detected in arterioles. LPA1 b...Continue Reading

References

Mar 11, 2000·American Journal of Physiology. Cell Physiology·H LeeS An
Apr 15, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·T S PanettiD F Mosher
Dec 16, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·G P van Nieuw AmerongenV W van Hinsbergh
Jun 19, 2002·JAMA : the Journal of the American Medical Association·Daniel L BakerGabor Tigyi
Jun 19, 2002·Biochimica Et Biophysica Acta·Tracee Scalise Panetti
Feb 8, 2003·Circulation Research·Hiroto MiuraDavid D Gutterman
Jul 9, 2003·The Journal of Biological Chemistry·Fernand GobeilSylvain Chemtob
Jul 24, 2004·Seminars in Cell & Developmental Biology·Junken Aoki
Aug 31, 2004·Journal of Thrombosis and Haemostasis : JTH·T S PanettiD F Mosher
Nov 24, 2006·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Sonia BraultSylvain Chemtob
Mar 6, 2007·American Journal of Physiology. Heart and Circulatory Physiology·C AvraamidesT S Panetti
Oct 10, 2007·Biochemical and Biophysical Research Communications·Chi-Iou LinHsinyu Lee
Jul 9, 2008·Journal of the American Chemical Society·Bryan C Dickinson, Christopher J Chang
Sep 6, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Francis KimMichael W Schwartz
Sep 22, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Yang-Ming YangDong Sun
Oct 6, 2009·Bioorganic & Medicinal Chemistry·James I FellsAbby L Parrill
Apr 3, 2010·Proceedings of the National Academy of Sciences of the United States of America·Harald M H G AlbersHuib Ovaa
Apr 16, 2010·The Journal of Pharmacology and Experimental Therapeutics·James GierseJaime Masferrer
Jan 5, 2011·Antioxidants & Redox Signaling·Michael E Widlansky, David D Gutterman
Jun 21, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Natalya S Zinkevich, David D Gutterman
Oct 11, 2011·Clinica Chimica Acta; International Journal of Clinical Chemistry·Tomotaka DohiHiroyuki Daida
Dec 14, 2011·Clinical Lipidology·Mei-Zhen Cui
May 15, 2013·Journal of Lipid Research·Ayca ErbilginAldons J Lusis
Oct 12, 2013·Biochemical and Biophysical Research Communications·Chu-Cheng LinHsinyu Lee
Nov 20, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Éva RuisanchezZoltán Benyó
Feb 8, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Manikandan PanchatcharamSusan S Smyth
Mar 7, 2014·The Journal of Biological Chemistry·Takashi BabaKatsuko Tani
Mar 19, 2014·Redox Biology·Rosa Bretón-Romero, Santiago Lamas
Apr 29, 2014·BioFactors·Elizabeth E-J Ha, Michael A Frohman
Sep 28, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Andreas M BeyerDavid D Gutterman
Nov 27, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Makoto KuranoYutaka Yatomi
Dec 5, 2014·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Michael A Frohman
May 15, 2015·Cellular and Molecular Life Sciences : CMLS·Emiliano Panieri, Massimo M Santoro
Dec 25, 2015·Circulation Research·Andreas M BeyerDavid D Gutterman
Apr 16, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Matthew J DurandAndreas M Beyer

❮ Previous
Next ❯

Citations

Nov 10, 2018·American Journal of Physiology. Heart and Circulatory Physiology·William E Hughes, Andreas M Beyer
Jun 9, 2020·Basic Research in Cardiology·William E HughesDavid D Gutterman
Apr 4, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Dawid S ChabowskiJulie K Freed
Nov 25, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·William E HughesDavid D Gutterman

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.