The Angiotensin-(1-12)/Chymase Axis As an Alternate Component of the Tissue Renin Angiotensin System

Overview

Journal Mol Cell Endocrinol

Specialties Cell Biology
Endocrinology
Molecular Biology

Date 2020 Dec 14

PMID 33309638

Citations 8

Authors

Carlos M Ferrario

Leanne Groban

Hao Wang

Che Ping Cheng

Jessica L VonCannon

Kendra N Wright

Xuming Sun

Sarfaraz Ahmad

Affiliations

Soon will be listed here.

Abstract

The identification of an alternate extended form of angiotensin I composed of the first twelve amino acids at the N-terminal of angiotensinogen has generated new knowledge of the importance of noncanonical mechanisms for renin independent generation of angiotensins. The human sequence of the dodecapeptide angiotensin-(1-12) [N-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Va-Ile-COOH] is an endogenous substrate that in the rat has been documented to be present in multiple organs including the heart, brain, kidney, gut, adrenal gland, and the bone marrow. Newer studies have confirmed the existence of Ang-(1-12) as an Ang II-forming substrate in the blood and heart of normal and diseased patients. Studies to-date document that angiotensin II generation from angiotensin-(1-12) does not require renin participation while chymase rather than angiotensin converting enzyme shows high catalytic activity in converting this tissue substrate into angiotensin II directly.

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References

Duengen H, Kim R, Zahger D, Orvin K, Kornowski R, Admon D . Effects of the chymase inhibitor fulacimstat on adverse cardiac remodeling after acute myocardial infarction-Results of the Chymase Inhibitor in Adverse Remodeling after Myocardial Infarction (CHIARA MIA) 2 trial. Am Heart J. 2020; 224:129-137. DOI: 10.1016/j.ahj.2020.01.012. View

Husain A, BUMPUS F, Smeby R, Brosnihan K, Khosla M, Speth R . Evidence for the existence of a family of biologically active angiotensin I-like peptides in the dog central nervous system. Circ Res. 1983; 52(4):460-4. DOI: 10.1161/01.res.52.4.460. View

Singh V, Le B, Bhat V, Baker K, Kumar R . High-glucose-induced regulation of intracellular ANG II synthesis and nuclear redistribution in cardiac myocytes. Am J Physiol Heart Circ Physiol. 2007; 293(2):H939-48. DOI: 10.1152/ajpheart.00391.2007. View

De Souza A, West C, de Abreu A, Pai A, Mesquita L, Ji H . Role of the Renin Angiotensin System in Blood Pressure Allostasis-induced by Severe Food Restriction in Female Fischer rats. Sci Rep. 2018; 8(1):10327. PMC: 6037681. DOI: 10.1038/s41598-018-28593-6. View

Ansary T, Urushihara M, Fujisawa Y, Nagata S, Urata H, Nakano D . Effects of the selective chymase inhibitor TEI-F00806 on the intrarenal renin-angiotensin system in salt-treated angiotensin I-infused hypertensive mice. Exp Physiol. 2018; 103(11):1524-1531. DOI: 10.1113/EP087209. View

Ahmad S, Varagic J, Groban L, DellItalia L, Nagata S, Kon N . Angiotensin-(1-12): a chymase-mediated cellular angiotensin II substrate. Curr Hypertens Rep. 2014; 16(5):429. PMC: 4007169. DOI: 10.1007/s11906-014-0429-9. View

Singh V, Le B, Khode R, Baker K, Kumar R . Intracellular angiotensin II production in diabetic rats is correlated with cardiomyocyte apoptosis, oxidative stress, and cardiac fibrosis. Diabetes. 2008; 57(12):3297-306. PMC: 2584136. DOI: 10.2337/db08-0805. View

Zhang M, Huang W, Bai J, Nie X, Wang W . Chymase inhibition protects diabetic rats from renal lesions. Mol Med Rep. 2016; 14(1):121-8. PMC: 4918600. DOI: 10.3892/mmr.2016.5234. View

Gwathmey T, Alzayadneh E, Pendergrass K, Chappell M . Novel roles of nuclear angiotensin receptors and signaling mechanisms. Am J Physiol Regul Integr Comp Physiol. 2011; 302(5):R518-30. PMC: 3311515. DOI: 10.1152/ajpregu.00525.2011. View

10.

Yamashita T, Ahmad S, Wright K, Roberts D, VonCannon J, Wang H . Noncanonical Mechanisms for Direct Bone Marrow Generating Ang II (Angiotensin II) Predominate in CD68 Positive Myeloid Lineage Cells. Hypertension. 2019; 75(2):500-509. PMC: 6949383. DOI: 10.1161/HYPERTENSIONAHA.119.13754. View

11.

Uijl E, Mirabito Colafella K, Sun Y, Ren L, Van Veghel R, Garrelds I . Strong and Sustained Antihypertensive Effect of Small Interfering RNA Targeting Liver Angiotensinogen. Hypertension. 2019; 73(6):1249-1257. DOI: 10.1161/HYPERTENSIONAHA.119.12703. View

12.

Urata H, Kinoshita A, Misono K, BUMPUS F, Husain A . Identification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart. J Biol Chem. 1990; 265(36):22348-57. View

13.

Kanefendt F, Thuss U, Becka M, Boxnick S, Berse M, Schultz A . Pharmacokinetics, Safety, and Tolerability of the Novel Chymase Inhibitor BAY 1142524 in Healthy Male Volunteers. Clin Pharmacol Drug Dev. 2018; 8(4):467-479. DOI: 10.1002/cpdd.579. View

14.

Jeunemaitre X, Gimenez-Roqueplo A, Celerier J, Corvol P . Angiotensinogen variants and human hypertension. Curr Hypertens Rep. 2000; 1(1):31-41. DOI: 10.1007/s11906-999-0071-0. View

15.

DellItalia L, Collawn J, Ferrario C . Multifunctional Role of Chymase in Acute and Chronic Tissue Injury and Remodeling. Circ Res. 2018; 122(2):319-336. PMC: 5776735. DOI: 10.1161/CIRCRESAHA.117.310978. View

16.

Leung P . Local RAS. Adv Exp Med Biol. 2010; 690:69-87. PMC: 7120160. DOI: 10.1007/978-90-481-9060-7_5. View

17.

Urata H, Kinoshita A, Perez D, Misono K, BUMPUS F, Graham R . Cloning of the gene and cDNA for human heart chymase. J Biol Chem. 1991; 266(26):17173-9. View

18.

Jessup J, Trask A, Chappell M, Nagata S, Kato J, Kitamura K . Localization of the novel angiotensin peptide, angiotensin-(1-12), in heart and kidney of hypertensive and normotensive rats. Am J Physiol Heart Circ Physiol. 2008; 294(6):H2614-8. PMC: 2561949. DOI: 10.1152/ajpheart.91521.2007. View

19.

Li T, Zhang Z, Zhang X, Chen Z, Cheng H, Ahmad S . Reversal of angiotensin-(1-12)-caused positive modulation on left ventricular contractile performance in heart failure: Assessment by pressure-volume analysis. Int J Cardiol. 2019; 301:135-141. PMC: 7888287. DOI: 10.1016/j.ijcard.2019.09.004. View

20.

Ferrario C, VonCannon J, Jiao Y, Ahmad S, Bader M, DellItalia L . Cardiac angiotensin-(1-12) expression and systemic hypertension in rats expressing the human angiotensinogen gene. Am J Physiol Heart Circ Physiol. 2016; 310(8):H995-1002. PMC: 4867338. DOI: 10.1152/ajpheart.00833.2015. View