# Integrative Analysis of VSMC, Macrophage, and Fibroblast Responses to LDLs in Aortic Pathologies

## TL;DR

This study explores how different aortic cells respond to LDLs, revealing pro-inflammatory changes that may contribute to cardiovascular diseases.

## Contribution

The novel contribution is the integrative analysis of VSMC, macrophage, and fibroblast responses to LDLs in aortic pathologies.

## Key findings

- All cell types internalize LDLs, with macrophages showing the highest lipid accumulation.
- VSMCs and fibroblasts exhibit pro-inflammatory features, including increased secretion of IL-6, IL-8, and CCL2.
- Macrophages show enhanced expression of CD36 and IL-1β after LDL exposure.

## Abstract

Cardiovascular diseases (CVDs) remain the leading cause of global mortality, with aortic pathologies such as atherosclerosis and thoracic aortic aneurysm posing significant risks due to their asymptomatic nature and potential fatal complications. This study investigates molecular mechanisms underlying CVDs by examining key cellular components of the aortic wall—vascular smooth muscle cells (VSMCs), fibroblasts, and macrophages—and their responses to low-density lipoproteins (LDLs). Using in vitro models, we analyzed phenotypic characteristics, LDL internalization capacity, and secretion/expression of pro-inflammatory mediators (IL-6, IL-8, IL-1β, CCL2) in primary VSMCs (from tunica intima and media), fibroblasts (977hTERT), and THP-1 macrophages. Fluorescence staining with BDP 630/650 revealed that all cell types internalize LDLs, with macrophages showing the highest lipid accumulation. ELISA and RT-qPCR demonstrated cell-specific patterns of cytokine secretion and gene expression, both in control conditions and after LDL exposure. The results indicate that VSMCs and fibroblasts, normally involved in vascular tone maintenance and extracellular matrix (ECM) synthesis, acquire pro-inflammatory features under pathological conditions, including increased secretion of IL-6, IL-8, and CCL2. Macrophages exhibited enhanced expression of the scavenger receptor CD36 and pro-inflammatory cytokines (especially IL-1β) after LDL treatment.