Molecular mechanism of lysophosphatidic acid-induced hypertensive response

Scientific Reports
Kuniyuki KanoJunken Aoki

Abstract

Lysophosphatidic acid (LPA) is a blood-derived bioactive lipid with numerous biological activities exerted mainly through six defined G protein-coupled receptors (LPA1-LPA6). LPA was first identified as a vasoactive compound because it induced transient hypertension when injected intravenously in rodents. Here, we examined the molecular mechanism underlying the LPA-induced hypertensive response. The LPA-induced hypertensive response was significantly attenuated by pretreatment with a Rho kinase inhibitor, which blocks Gα12/13 signaling. Consistent with this, the response was weakened in KO mice of LPA4, a Gα12/13-coupling LPA receptor. KO mice of another Gα12/13-coupling LPA receptor, LPA6, also showed an attenuated LPA-induced hypertensive response. However, LPA6 KO mice also displayed attenuated pressor responses to an adrenergic agent and abnormal blood vessel formation. Using several LPA analogs with varied affinity for each LPA receptor, we found a good correlation between the hypertensive and LPA4 agonistic activities. Incubated mouse plasma, which contained abundant LPA, also induced a hypertensive response. Interestingly the response was completely abolished when the plasma was incubated in the presence of an ATX inhibi...Continue Reading

References

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Citations

May 16, 2020·The Journal of Pharmacology and Experimental Therapeutics·Etienne GuillotChristophe Philippo
Apr 4, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Dawid S ChabowskiJulie K Freed
Aug 26, 2020·Metabolites·Alec Millner, G Ekin Atilla-Gokcumen
Sep 19, 2020·The Journal of Physiology·Thieu X PhanGerard P Ahern
Dec 18, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Eric EngelbrechtTimothy Hla
Feb 3, 2021·Signal Transduction and Targeted Therapy·Luiz Henrique Medeiros GeraldoFlavia Regina Souza Lima
May 8, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Susan S SmythAndrew J Morris
Jul 3, 2021·International Journal of Molecular Sciences·Karina Helivier SolísJ Adolfo García-Sáinz
Jun 15, 2021·European Journal of Medicinal Chemistry·Bhagyalalitha MeduriBijo Mathew

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