Recombinant Human ACE2 and the Angiotensin 1-7 Axis as Potential New Therapies for Heart Failure

Area of Science:

• Cardiology
• Biochemistry
• Pharmacology

Background:

• Heart failure (HF) is a leading cause of death and disability, with significant economic impact.
• Current therapies for HF with reduced ejection fraction (HF-rEF) target the renin-angiotensin system, but effective treatments for HF with preserved ejection fraction (HF-pEF) are lacking.
• The renin-angiotensin system plays a crucial role in HF progression, with Angiotensin II (Ang II) contributing to adverse cardiac remodeling.

Purpose of the Study:

• To review the role of the ACE2/Ang 1-7 axis in heart failure.
• To explore the potential of targeting the ACE2/Ang 1-7 pathway as a therapeutic strategy for both HF-rEF and HF-pEF.
• To summarize the cardioprotective mechanisms of the ACE2/Ang 1-7 axis.

Main Methods:

• Review of preclinical and clinical studies on the renin-angiotensin system in heart failure.
• Analysis of the function and regulation of Angiotensin-Converting Enzyme 2 (ACE2) and Angiotensin 1-7 (Ang 1-7).
• Evaluation of the therapeutic potential of enhancing the ACE2/Ang 1-7 axis in HF models.

Main Results:

• The ACE/Ang II/Ang II type 1 receptor axis is activated in HF and targeted by current therapies, mainly for HF-rEF.
• ACE2 converts Ang II to Ang 1-7, exerting counter-regulatory and cardioprotective effects.
• Preclinical studies demonstrate that enhancing ACE2 or Ang 1-7 provides benefits in both HF-pEF and HF-rEF models, including improved endothelial function, reduced inflammation and fibrosis, and corrected metabolic dysfunction.

Conclusions:

• The ACE2/Ang 1-7 axis represents a promising therapeutic target for heart failure, potentially offering benefits for both HF-pEF and HF-rEF.
• Further clinical evaluation of recombinant human ACE2 and Ang 1-7 is warranted to assess their efficacy in HF patients.
• Targeting the ACE2/Ang 1-7 pathway could overcome limitations of current HF pharmacotherapies.