# The role of macrophages in vascular calcification: strategies for diagnosis and treatment

## TL;DR

Macrophages influence vascular calcification through different roles, and this review explores their mechanisms, diagnosis, and treatment strategies.

## Contribution

This review systematically summarizes macrophage polarization mechanisms and proposes future immunomodulation-based therapies for vascular calcification.

## Key findings

- Pro-inflammatory macrophages promote calcification through various mechanisms.
- Anti-inflammatory macrophages can inhibit calcification but may become pro-calcific in diabetes.
- Therapeutic strategies targeting macrophage polarization and activation are highlighted.

## Abstract

Vascular calcification (VC) is an actively regulated pathological process that significantly increases the risk of cardiovascular events. As key cells of the innate immune system, macrophages play a dual role in VC through polarization into different phenotypes: Pro-inflammatory macrophages promote calcification by secreting pro-inflammatory factors, releasing apoptotic bodies, and producing extracellular vesicles (EVs); conversely, Anti-inflammatory macrophages inhibit calcification through anti-inflammatory factors, exosomes, plaque stabilization, and ATP/pyrophosphate (PPi) metabolism. However, under metabolic diseases such as diabetes, anti-inflammatory macrophages may exhibit pro-calcific properties. This review systematically summarizes the mechanisms of macrophage polarization in VC, discusses the application of macrophage-related biomarkers and imaging techniques in diagnosis, and highlights therapeutic strategies targeting macrophage polarization, recruitment, and activation. Finally, current challenges in dynamically monitoring macrophage polarization and context-dependent functional heterogeneity are outlined, and future research directions focusing on immunomodulation-based multi-target drug design and engineered cell therapies are proposed.