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Purpose of review <p>This review examines the protective angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas receptor axis of the renin–angiotensin system. We sought to integrate evidence from preclinical and early human studies on how activation of this pathway influences vascular, cardiac, renal, hepatic and metabolic health, and to identify methodological lessons for developing future therapies.</p> Recent findings <p>Animal models show that augmenting this axis improves endothelial function, limits cardiac remodelling, enhances insulin sensitivity, reduces renal injury and mitigates hepatic steatosis associate with MASH/NAFLD. Early-phase trials of recombinant angiotensin-converting enzyme 2 and angiotensin-(1–7) analogues demonstrate favourable safety profiles and clear pharmacodynamic target engagement but inconsistent immediate clinical effects. Emerging work highlights the value of biomarker ratios, gene and lifestyle based modulation and patient stratification strategies.</p> Summary <p>Activation of the angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas receptor axis offers a promising route to address cardiometabolic disease. Filling gaps in long-term outcomes, receptor-specific mechanisms and precision patient selection could transform this counter-regulatory pathway into a cornerstone of next-generation therapies.</p>

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Therapeutic Opportunities Targeting the ACE2/Ang-(1–7)/MasR Pathway in Cardiometabolic Disease

  • 期刊论文

  • 发表日期：

    2026年3月16日

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  • Thilina U. Jayawardena,
  • Dineth P. Nagahawatta,
  • Maria B. Grant,
  • Mark C. Chappell,
  • Gavin Y. Oudit

摘要

Purpose of review

This review examines the protective angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas receptor axis of the renin–angiotensin system. We sought to integrate evidence from preclinical and early human studies on how activation of this pathway influences vascular, cardiac, renal, hepatic and metabolic health, and to identify methodological lessons for developing future therapies.

Recent findings

Animal models show that augmenting this axis improves endothelial function, limits cardiac remodelling, enhances insulin sensitivity, reduces renal injury and mitigates hepatic steatosis associate with MASH/NAFLD. Early-phase trials of recombinant angiotensin-converting enzyme 2 and angiotensin-(1–7) analogues demonstrate favourable safety profiles and clear pharmacodynamic target engagement but inconsistent immediate clinical effects. Emerging work highlights the value of biomarker ratios, gene and lifestyle based modulation and patient stratification strategies.

Summary

Activation of the angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas receptor axis offers a promising route to address cardiometabolic disease. Filling gaps in long-term outcomes, receptor-specific mechanisms and precision patient selection could transform this counter-regulatory pathway into a cornerstone of next-generation therapies.