Angiotensin-(1-7) vs Apelin

Both are cardiovascular peptides that tend to oppose angiotensin II effects. Angiotensin-(1-7) comes from ACE2 processing and acts on Mas; apelin acts on the APJ receptor. ACE2 also cleaves apelin, linking the two.

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Angiotensin-(1-7)

A heptapeptide of the renin–angiotensin system that tends to counter angiotensin II — the "protective arm" of the ACE2/Ang-(1-7)/Mas axis.

BEST STUDIED FOR

Repair & immune

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Apelin

An endogenous peptide ligand of the APJ receptor, studied as an "exerkine" released by muscle during exercise.

BEST STUDIED FOR

Mitochondrial & longevity

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SIDE BY SIDE

	Angiotensin-(1-7)	Apelin
The key difference	Renin–angiotensin peptide, Mas receptor	APJ-receptor peptide
Class	Repair & immune	Mitochondrial & longevity
Mechanism	ACE2 converts angiotensin II into angiotensin-(1-7), which acts mainly through the Mas receptor.	Apelin/APJ signalling is widespread (heart, vessels, muscle, brain).
Status	Investigational. Early clinical trials include intravenous infusion in ICU COVID-19 patients and an oral cyclodextrin formulation in athletes; not an approved medicine.	Preclinical and translational research; apelin-pathway agonists are being explored in cardiovascular disease.
Reported safety signals	A phase 1–2 ICU trial reported the infusion as safe, with one serious adverse event (bradycardia) considered possibly related; it showed no significant difference in its phase 2 outcome.	No therapeutic human safety data for apelin itself.
A key study	A major review of the ACE2/angiotensin-(1-7)/Mas axis and its counter-regulatory role in the renin–angiotensin system. (Physiol Rev 2018, PMID 29351514)	Found apelin is exercise-induced, declines with age, and reversed age-related muscle loss in mice. (Nat Med 2018, PMID 30061698)

WHEN TO RESEARCH WHICH

Both suit cardiovascular counter-regulation research; neither is an approved medicine. Both are discussed here strictly as research compounds; nothing on this page is medical advice or a dosing guide.

REFERENCES (PUBMED)

[Angiotensin-(1-7)] The ACE2/Angiotensin-(1-7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1-7) — Physiol Rev 2018. PMID 29351514
[Angiotensin-(1-7)] Angiotensin-(1-7) infusion in COVID-19 patients admitted to the ICU: a seamless phase 1-2 randomized clinical trial — Ann Intensive Care 2024. PMID 39231898
[Angiotensin-(1-7)] Effects of oral HPΒCD-angiotensin-(1-7) supplementation on recreational mountain bike athletes: a crossover study — Phys Sportsmed 2024. PMID 36752064
[Apelin] The exerkine apelin reverses age-associated sarcopenia — Nat Med 2018. PMID 30061698
[Apelin] Targeting the apelin system for the treatment of cardiovascular diseases — Cardiovasc Res 2023. PMID 37956047
[Apelin] Apelin regulates skeletal muscle adaptation to exercise in a high-intensity interval training model — Am J Physiol Cell Physiol 2024. PMID 38525542

FREQUENTLY ASKED

What is the difference between Angiotensin-(1-7) and Apelin?

What is the regulatory status of Angiotensin-(1-7) and Apelin?

Angiotensin-(1-7): Investigational. Early clinical trials include intravenous infusion in ICU COVID-19 patients and an oral cyclodextrin formulation in athletes; not an approved medicine. Apelin: Preclinical and translational research; apelin-pathway agonists are being explored in cardiovascular disease.

What safety signals have been reported?

Angiotensin-(1-7): A phase 1–2 ICU trial reported the infusion as safe, with one serious adverse event (bradycardia) considered possibly related; it showed no significant difference in its phase 2 outcome. Apelin: No therapeutic human safety data for apelin itself.

Which studies is this comparison based on?

For Angiotensin-(1-7): “The ACE2/Angiotensin-(1-7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1-7)” (PMID 29351514); “Angiotensin-(1-7) infusion in COVID-19 patients admitted to the ICU: a seamless phase 1-2 randomized clinical trial” (PMID 39231898); “Effects of oral HPΒCD-angiotensin-(1-7) supplementation on recreational mountain bike athletes: a crossover study” (PMID 36752064). For Apelin: “The exerkine apelin reverses age-associated sarcopenia” (PMID 30061698); “Targeting the apelin system for the treatment of cardiovascular diseases” (PMID 37956047); “Apelin regulates skeletal muscle adaptation to exercise in a high-intensity interval training model” (PMID 38525542).