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REVIEW

Monocyte Phenotypic Plasticity in Peripheral Artery Disease: From Pathophysiology to Therapeutic Targets

Gizem Kaynar Beyaz1,*, Ahmet Kirbas2, Sevgi Kalkanli Tas1
1 Hamidiye Health Sciences Institute, Department of Immunology, Health Sciences University, Istanbul, 34668, Türkiye
2 Umraniye Training and Research Hospital, Department of Cardiovascular Surgery, Health Sciences University, Istanbul, 34760, Türkiye
* Corresponding Author: Gizem Kaynar Beyaz. Email: email
(This article belongs to the Special Issue: Mechanisms Driving COPD, Atherosclerosis, and Cardiovascular Disease: From Pathogenesis to Therapeutic Innovations)

BIOCELL https://doi.org/10.32604/biocell.2025.072368

Received 25 August 2025; Accepted 15 October 2025; Published online 26 November 2025

Abstract

Peripheral artery disease (PAD) remains a significant global health issue, with current treatments primarily focused on relieving symptoms and addressing macrovascular issues. However, critical immunoinflammatory mechanisms are often overlooked. Recent evidence suggests that monocyte phenotypic plasticity plays a central role in PAD development, affecting atherogenesis, plaque progression, ischemia-reperfusion injury, and chronic ischemic remodeling. This narrative review aims to summarize the latest advances (2023–2025) in understanding monocyte diversity, functional states, and their changes throughout different stages of PAD. We discuss both established and emerging biomarkers, such as circulating monocyte subset proportions, functional assays, immune checkpoint expression, and multi-omics signatures, highlighting their potential for prognosis and the challenges in translating them to clinical practice. We also present a stage-specific approach to mapping out potential therapies, linking monocyte phenotypes to molecular targets and possible interventions. Additionally, we address regulatory, economic, and implementation considerations for applying these findings in a clinical setting. The goal of this review is to facilitate the development of targeted immunomodulatory strategies to improve limb and cardiovascular outcomes in PAD by combining mechanistic understanding with therapeutic innovation.

Keywords

Peripheral artery disease; monocytes; phenotypic plasticity; immunomodulation; therapeutic targets

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