# Research Progress of Annexin A1 and Its Derived Peptides in the Diagnosis and Treatment of Circulatory Diseases

## TL;DR

Annexin A1 and its peptides may help diagnose and treat circulatory diseases by reducing inflammation and protecting cells.

## Contribution

This review highlights new insights into Annexin A1's role and derived peptides in circulatory diseases, emphasizing their therapeutic potential.

## Key findings

- Annexin A1 peptides reduce inflammation and oxidative stress in circulatory diseases.
- Peptides like Ac2-26 and RTP-026 show protective effects through pathways like SIRT3 and PI3K/Akt.
- Annexin A1's effects vary by disease context, requiring specific investigations.

## Abstract

Annexin A1 (ANXA1), a calcium‐dependent phospholipid‐binding protein, plays a critical role in regulating inflammation, apoptosis, immune responses, and vascular remodeling. It is increasingly recognized for its potential as a therapeutic target and diagnostic biomarker in various circulatory diseases, including sepsis, hypertension, coronary heart disease, myocardial ischemia‐reperfusion injury, heart failure, and cerebrovascular disorders. ANXA1 and its derived peptides exert protective effects by modulating key signaling pathways and cellular processes involved in disease pathogenesis.

This review summarizes the current research progress on ANXA1 and its derived peptides in the diagnosis and treatment of circulatory diseases, highlighting their mechanisms of action and therapeutic potential.

A comprehensive literature search was conducted using PubMed, Web of Science, and other relevant databases. Articles published up to 2024 were included, with a focus on experimental studies, clinical reports, and reviews addressing the role of ANXA1 in circulatory diseases. Key themes included anti‐inflammatory mechanisms, apoptosis regulation, immune modulation, and vascular protection.

ANXA1 and its mimetic peptides like Ac2‐26, ANXA1sp, RTP‐026 and so on demonstrate significant protective effects across multiple circulatory diseases. They attenuate inflammation, oxidative stress, apoptosis, and ferroptosis, while promoting mitochondrial biosynthesis and immune regulation. These effects are mediated through receptors such as FPR2/ALX and pathways involving SIRT3, PI3K/Akt, and AMPK/mTOR. However, the role of ANXA1 can be context‐dependent, exhibiting both protective and detrimental effects in specific conditions such as gestational hypertension and transient ischemic attack.

ANXA1 represents a promising diagnostic biomarker and therapeutic target for circulatory diseases. Further research is needed to elucidate its complex regulatory networks and validate its clinical applicability through multi‐omics approaches and large‐scale trials.

ANXA1 regulates inflammation, apoptosis, and immune responses in circulatory diseases.Derived peptides mimic ANXA1's bioactivity and show therapeutic potential.ANXA1's role is context‐dependent, requiring disease‐specific investigation.Future studies should integrate omics technologies and clinical validation to optimize ANXA1‐based interventions.

ANXA1 regulates inflammation, apoptosis, and immune responses in circulatory diseases.

Derived peptides mimic ANXA1's bioactivity and show therapeutic potential.

ANXA1's role is context‐dependent, requiring disease‐specific investigation.

Future studies should integrate omics technologies and clinical validation to optimize ANXA1‐based interventions.