Oxidized LDL but not angiotensin II induces the interaction between LOX-1 and AT1 receptors

Lin, L.; Zhou, N.; Kang, L.; Wang, Q.; Wu, J.; Wang, X.; Yang, C.; Zhang, G.; Chen, Y.; Jiang, H.; Chen, R.; Yang, X.; Sun, A.; Gong, H.; Ren, J.; Akazawa, H.; KOMURO, I.; Ge, J.; Zou, Y.

doi:10.1101/2020.12.14.422633

bioRxiv · 10.1101/2020.12.14.422633

Oxidized LDL but not angiotensin II induces the interaction between LOX-1 and AT1 receptors

Lin, L.·Zhou, N.·Kang, L.·Wang, Q.·Wu, J.·Wang, X.·Yang, C.·Zhang, G.·Chen, Y.·Jiang, H.·Chen, R.·Yang, X.·Sun, A.·Gong, H.·Ren, J.·Akazawa, H.·KOMURO, I.·Ge, J.·Zou, Y.

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Abstract

Oxidized low-density lipoprotein (Ox-LDL) can induce cardiac hypertrophy, but the mechanism is still unclear. Here we elucidate the role of angiotensin II (AngII) receptor (AT1-R) in Ox-LDL-induced cardiomycyte hypertrophy. Inhibition of Ox-LDL receptor LOX-1 and AT1-R rather than AngII abolished Ox-LDL-induced hypertrophic responses. Similar results were obtained from the heart of mice lacking endogenous Ang II and their cardiomyocytes. Ox-LDL but not AngII induced binding of LOX-1 to AT1-R, and the inhibition of LOX-1 or AT1-R rather than AngII abolished the association of these two receptors. Ox-LDL-induced ERKs phosphorylation in LOX-1 and AT1-R-overexpression cells and the binding of both receptors were suppressed by the mutants of LOX-1 (Lys266Ala/Lys267Ala) or AT1-R (Glu257Ala), however, the AT1-R mutant lacking Gq protein-coupling ability only abolished the ERKs phosphorylation. The phosphorylation of ERKs induced by Ox-LDL in LOX-1 and AT1-R-overexpression cells was abrogated by Gq protein inhibitor but not by Jak2, Rac1 and RhoA inhibitors. Therefore, the direct interaction between LOX-1 and AT1-R and the downstream Gq protein activation are important mechanisms for Ox-LDL-but not AngII-induced cardiomyocyte hypertrophy.

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Lin, L., Zhou, N., Kang, L., Wang, Q., Wu, J., Wang, X., Yang, C., Zhang, G., Chen, Y., Jiang, H., Chen, R., Yang, X., Sun, A., Gong, H., Ren, J., Akazawa, H., KOMURO, I., Ge, J., Zou, Y.. 2020-12-14. Oxidized LDL but not angiotensin II induces the interaction between LOX-1 and AT1 receptors. https://doi.org/10.1101/2020.12.14.422633

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