Angiotensin (1-7) Explained

Symbol:Angiotensin (1-7)
Angiotensin (1-7)
Scop:2PJ8

Angiotensin (1-7) (; Molecular weight = 899.02 g/mol; H-Asp-Arg-Val-Tyr-Ile-His-Pro-OH) is an active heptapeptide of the renin–angiotensin system (RAS). It also known by the generic name talfirastide (development name TXA127).[1]

In 1988, Santos et al demonstrated that angiotensin (1-7) was a main product of the incubation of angiotensin I with brain micropunch biopsies[2] and Schiavone et al reported the first biological effect of this heptapeptide.[3]

Angiotensin (1-7) is a vasodilator agent affecting cardiovascular organs, such as heart, blood vessels and kidneys, with functions frequently opposed to those attributed to the major effector component of the RAS, angiotensin II (Ang II).[4]

Synthesis

The polypeptide Ang I can be converted into Ang (1-7) by the actions of neprilysin (NEP)[5] and thimet oligopeptidase (TOP)[6] enzymes. Also, Ang II can be hydrolyzed into Ang (1-7) through the actions of angiotensin-converting enzyme 2 (ACE2). Ang (1-7) binds and activates the G-protein coupled receptor Mas receptor[7] leading to opposite effects of those of Ang II.

Possible pathways

Effects

Ang (1-7) has been shown to have anti-oxidant and anti-inflammatory effects.[8] [9] It helps protect cardiomyocytes of spontaneously hypertensive rats by increasing the expression of endothelial and neuronal nitric oxide synthase enzymes, augmenting production of nitric oxide.[10]

Pharmacological interactions

Ang (1-7) contributes to the beneficial effects of ACE inhibitors and angiotensin II receptor type 1 antagonists.[11]

Clinical trials

Talfirastide has been tested in people with COVID-19[12] and stroke.[13]

Notes and References

  1. 2 . Wagener . Gebhard . Goldklang . Monica P. . Gerber . Adam . Elisman . Katerina . Eiseman . Katherine A. . Fonseca . Laura D. . D’Armiento . Jeanine M. . A randomized, placebo-controlled, double-blinded pilot study of angiotensin 1–7 (TXA-127) for the treatment of severe COVID-19 . Critical Care . 28 July 2022 . 26 . 1 . 229 . 10.1186/s13054-022-04096-9 . 35902867 . 9332096 . 1364-8535 . free .
  2. Santos RA, Brosnihan KB, Chappell MC, Pesquero J, Chernicky CL, Greene LJ, and Ferrario CM . Converting enzyme activity and angiotensin metabolism in the dog brainstem . Hypertension . 11 . 2 . 125–37 . 1988 . 10.1161/01.hyp.11.2_pt_2.i153 . 2831145 . 280369 .
  3. Schiavone MT, Santos RA, Brosnihan KB, Khosla MC, Ferrario CM . Release of vasopressin from the rat hypothalamo-neurohypophysial system by angiotensin-(1-7) heptapeptide . PNAS . 85 . 11 . 4095–8 . 1988 . 10.1073/pnas.85.11.4095 . 3375255 . 280369 . 1988PNAS...85.4095S . free .
  4. Santos RA, Sampaio WO, Alzamora AC, Motta-Santos D, Alenina N, Bader M, et al . The ACE2/Angiotensin-(1-7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1-7) . Physiol Rev . 1 . 98 . 505–553 . 2018 . 10.1152/physrev.00023.2016 . 29351514 . 7203574 .
  5. Chappell MC . Biochemical evaluation of the renin-angiotensin system: the good, bad, and absolute? . American Journal of Physiology. Heart and Circulatory Physiology . 310 . 2 . H137-52 . January 2016 . 26475588 . 4796631 . 10.1152/ajpheart.00618.2015 .
  6. Wilson BA, Nautiyal M, Gwathmey TM, Rose JC, Chappell MC . Evidence for a mitochondrial angiotensin-(1-7) system in the kidney . American Journal of Physiology. Renal Physiology . 310 . 7 . F637–F645 . April 2016 . 26697984 . 4824145 . 10.1152/ajprenal.00479.2015 .
  7. Santos RA, Simoes e Silva AC, Maric C, Silva DM, Machado RP, de Buhr I, Heringer-Walther S, Pinheiro SV, Lopes MT, Bader M, Mendes EP, Lemos VS, Campagnole-Santos MJ, Schultheiss HP, Speth R, Walther T . Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas . Proceedings of the National Academy of Sciences of the United States of America . 100 . 14 . 8258–63 . July 2003 . 12829792 . 166216 . 10.1073/pnas.1432869100 . 2003PNAS..100.8258S . free .
  8. Benter IF, Yousif MH, Dhaunsi GS, Kaur J, Chappell MC, Diz DI . Angiotensin-(1-7) prevents activation of NADPH oxidase and renal vascular dysfunction in diabetic hypertensive rats . American Journal of Nephrology . 28 . 1 . 25–33 . 2008 . 17890855 . 10.1159/000108758 . 24219314 .
  9. El-Hashim AZ, Renno WM, Raghupathy R, Abduo HT, Akhtar S, Benter IF . Angiotensin-(1-7) inhibits allergic inflammation, via the MAS1 receptor, through suppression of ERK1/2- and NF-κB-dependent pathways . British Journal of Pharmacology . 166 . 6 . 1964–76 . July 2012 . 22339213 . 3402818 . 10.1111/j.1476-5381.2012.01905.x .
  10. Zisman LS, Meixell GE, Bristow MR, Canver CC . Angiotensin-(1-7) formation in the intact human heart: in vivo dependence on angiotensin II as substrate . Circulation . 108 . 14 . 1679–81 . October 2003 . 14504185 . 10.1161/01.CIR.0000094733.61689.D4 . free .
  11. Benter IF, Yousif MH, Al-Saleh FM, Raghupathy R, Chappell MC, Diz DI . Angiotensin-(1-7) blockade attenuates captopril- or hydralazine-induced cardiovascular protection in spontaneously hypertensive rats treated with NG-nitro-L-arginine methyl ester . Journal of Cardiovascular Pharmacology . 57 . 5 . 559–67 . May 2011 . 21326110 . 3095755 . 10.1097/FJC.0b013e31821324b6 .
  12. Self . Wesley H. . Shotwell . Matthew S. . Gibbs . Kevin W. . de Wit . Marjolein . Files . D. Clark . Harkins . Michelle . Hudock . Kristin M. . Merck . Lisa H. . Moskowitz . Ari . Apodaca . Krystle D. . Barksdale . Aaron . Safdar . Basmah . Javaheri . Ali . Sturek . Jeffrey M. . Schrager . Harry . Iovine . Nicole . Tiffany . Brian . Douglas . Ivor S. . Levitt . Joseph . Busse . Laurence W. . Ginde . Adit A. . Brown . Samuel M. . Hager . David N. . Boyle . Katherine . Duggal . Abhijit . Khan . Akram . Lanspa . Michael . Chen . Peter . Puskarich . Michael . Vonderhaar . Derek . Venkateshaiah . Lokesh . Gentile . Nina . Rosenberg . Yves . Troendle . James . Bistran-Hall . Amanda J. . DeClercq . Josh . Lavieri . Robert . Joly . Meghan Morrison . Orr . Michael . Pulley . Jill . Rice . Todd W. . Schildcrout . Jonathan S. . Semler . Matthew W. . Wang . Li . Bernard . Gordon R. . Collins . Sean P. . Becker . Richard C. . del Zoppo . Gregory . Henke . Peter . Holubkov . Richard . Johnson . Maryl . Kerr . Kim . Lipman . Hannah I. . Lurie . Fedor . Pitt . Bertram . Vesely . Sara K. . Fleg . Jerome L. . Aamodt . Dave . Ayers . J'Mario . Clark . Debra . Collins . Jessica . Cook . Maya . Dixon . Sheri . Graves . John . Jordan . Courtney . Lindsell . Christopher J. . Lopez . Itzel . McKeel . David . Orozco . Dirk . Prato . Nelson . Qi . Ally . Qutab . Madiha . Stoughton . Christa . Vermillion . Krista . Walsh . Kelly . Winchell . Stephanie . Young . Taylor . Franklin . Richard . Wagner . Elizabeth . Walther . Thomas . Demitrack . Mark . Johnson . Jakea . Walsh . Ryan . Bales . Brian . Miller . Karen . Torr . Donna . Barot . Harsh . Landreth . Leigha . LaRose . Mary . Parks . Lisa . Teixeira . J. Pedro . Cardenas . Sandra . Ceniceros . Juan A. . Cunningham . Amy G. . Kunkel . Susan . Lovato . Debbie M. . Zimmerman . Brooklin . Nguyen . Thanh . Zeger . Wesley . Nichols . Heather . Wiedel . Noah . Javaheri . Ali . Stilinovic . Stephanie . Brokowski . Carolyn . Lu . Jing . Solberg . Muriel . Lee . Dana . Roach . Kristopher . Tiffany . Brian . Tanner . Charlotte . Taylor . Annette . Zumbahl . Jennine . Syed . Aamer . Mason . Jessica . Jackson . Patrick E. H. . Coleman . Rachael W. . Haughey . Heather M. . Cherabuddi . Kartik . James . Nastasia . Wakeman . Rebecca . Duncan . Christopher . Montero . Cynthia . Rogers . Angela J. . Wilson . Jennifer G. . Vojnik . Rosemary . Perez . Cynthia . Wyles . David . Hiller . Terra D. . Oakes . Judy L. . Garcia . Ana Z. . Gong . Michelle . Mohamed . Amira . Andrea . Luke . Nair . Rahul . Nkemdirim . William . Lopez . Brenda . Boujid . Sabah . Torres . Martha . Garcia . Ofelia . Martinez . Flora . Baduashvili . Amiran . Bastman . Jill . Chauhan . Lakshmi . Douin . David J. . Finck . Lani . Licursi . Ashley . ten Lohuis . Caitlin . Zhang . Sophia . Bender . William . Tovar . Santiago . Hayes . Sharon . Kurtzman . Nicholas . Rosseto . Elinita . Scaffidi . Douglas . Shapiro . Nathan . Pak . Jonathan . Allada . Gopal . Briceno . Genesis . Peña . Jose . Oh . Minn . Ali . Harith . Beselman . Sasha . Eby . Yolanda . Klimov . Vitaliy . Hite . R. Duncan . Tanzeem . Hammad . Droege . Chris . Winter . Jessica . Jackman . Susan . Caudill . Antonina . Bayoumi . Emad . Pascual . Ethan . Chen . Po-En . Mucha . Simon . Thiruchelvam . Nirosshan . Siuba . Matthew . Mehkri . Omar . Driver . Brian E. . Hendrickson . Audrey F. . Kaus . Olivia R. . Ontiveros . Christina . Riehm . Amy . Laudun . Sylvia . Hudock . Debra . Ensley . Christopher . Shaner . Valerie . Gentile . Nina . Isenberg . Derek . Reimer . Hannah . Cincola . Paul . Harris . Estelle S. . Callahan . Sean J. . Yamane . Misty B. . Barrios . Macy AG . Desai . Neeraj . Bharara . Amit . Keller . Michael . Majumder . Prat . Dohe . Carrie . D’Armiento . Jeanine . Goldklang . Monica . Wagener . Gebhard . Fonseca . Laura . Valezquez-Sanchez . Itzel . Johnson . Nicholas J. . Petersen . Emily . Fuentes . Megan . Newton . Maranda . Gundel . Stephanie . Srinivasan . Vasisht . Steel . Tessa . Robinson . Bryce . 2 . Renin-Angiotensin System Modulation With Synthetic Angiotensin (1-7) and Angiotensin II Type 1 Receptor–Biased Ligand in Adults With COVID-19: Two Randomized Clinical Trials . JAMA . 11 April 2023 . 329 . 14 . 1170–1182 . 10.1001/jama.2023.3546. 37039791 . 258062415 . free . 10091180 .
  13. Web site: Phase 2 Study of TXA127 in Post-ischemic Stroke Patients - Full Text View - ClinicalTrials.gov . clinicaltrials.gov . 7 December 2023 . en.

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