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Research ArticleMinireview

Targeting the Protective Arm of the Renin-Angiotensin System: Focused on Angiotensin-(1–7)

Sana Khajehpour and Ali Aghazadeh-Habashi
Journal of Pharmacology and Experimental Therapeutics April 2021, 377 (1) 64-74; DOI: https://doi.org/10.1124/jpet.120.000397
Sana Khajehpour
Department of Biomedical and Pharmaceutical Sciences, Idaho State University, Pocatello, ID
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Ali Aghazadeh-Habashi
Department of Biomedical and Pharmaceutical Sciences, Idaho State University, Pocatello, ID
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  • ORCID record for Ali Aghazadeh-Habashi
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Abstract

The in vivo application and efficacy of many therapeutic peptides is limited because of their instability and proteolytic degradation. Novel strategies for developing therapeutic peptides with higher stability toward proteolytic degradation would be extremely valuable. Such approaches could improve systemic bioavailability and enhance therapeutic effects. The renin-angiotensin system (RAS) is a hormonal system within the body essential for the regulation of blood pressure and fluid balance. The RAS is composed of two opposing classic and protective arms. The balance between these two arms is critical for the homeostasis of the body’s physiologic function. Activation of the RAS results in the suppression of its protective arm, which has been reported in inflammatory and pathologic conditions such as arthritis, cardiovascular diseases, diabetes, and cancer. Clinical application of angiotensin-(1–7) [Ang-(1–7)], a RAS critical regulatory peptide, augments the protective arm and restores balance hampered by its enzymatic and chemical instability. Several attempts to increase the half-life and efficacy of this heptapeptide using more stable analogs and different drug delivery approaches have been made. This review article provides an overview of efforts targeting the RAS protective arm. It provides a critical analysis of Ang-(1–7) or its homologs’ novel drug delivery systems using different administration routes, their pharmacological characterization, and therapeutic potential in various clinical settings.

SIGNIFICANCE STATEMENT Ang-(1–7) is a unique peptide component of the renin-angiotensin system with vast potential for clinical applications that modulate various inflammatory diseases. Novel Ang-(1–7) peptide drug delivery could compensate its lack of stability for effective clinical application.

Footnotes

    • Received October 27, 2020.
    • Accepted January 19, 2021.
  • https://doi.org/10.1124/jpet.120.000397.

  • Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 377 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 377, Issue 1
1 Apr 2021
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Research ArticleMinireview

Targeting the Protective Arm of the Renin-Angiotensin System

Sana Khajehpour and Ali Aghazadeh-Habashi
Journal of Pharmacology and Experimental Therapeutics April 1, 2021, 377 (1) 64-74; DOI: https://doi.org/10.1124/jpet.120.000397

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Research ArticleMinireview

Targeting the Protective Arm of the Renin-Angiotensin System

Sana Khajehpour and Ali Aghazadeh-Habashi
Journal of Pharmacology and Experimental Therapeutics April 1, 2021, 377 (1) 64-74; DOI: https://doi.org/10.1124/jpet.120.000397
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    • Targeting the RAS Classic Arm
    • Targeting the RAS Protective Arm
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