The extracellular matrix as a mediator of cell-cell communication in cardiovascular inflammation

Introduction

Cardiovascular diseases, such as coronary artery disease (CAD) and its sequelae myocardial infarction (MI) and heart failure, represent the leading cause of morbidity and mortality in industrialized and developing countries. Atherosclerosis is the pathology causing CAD and MI; both are characterized by a sterile inflammation with a chronic and acute course of the disease, respectively.

Role of Cell Types

There is a plethora of cell types involved in these diseases, including:

• Leukocytes
• Endothelial cells
• Vascular smooth muscle cells
• Platelets
• Fibroblasts
• Cardiomyocytes

These cell types play important roles in the initiation, propagation, and termination of the pathophysiological processes.

Genetic Insights

Recent data from genetic studies have found that genetic variation influencing extracellular matrix (ECM) proteins is associated with cardiovascular diseases. We discovered that such proteins, which are secreted by one cell type, influence the phenotypes of other cell types through mechanisms such as:

• Silencing of inflammatory functions
• Modulation of ECM composition

ECM as a Communication Hub

The ECM represents not only a meshwork in which cells are organized but also a communication hub that transduces mechanical stimuli and cell-cell interaction signals.

Research Objectives

Here, we aim to explore the ECM proteome in sterile inflammatory diseases such as atherosclerosis and MI in unprecedented depth. Our objectives include:

1. Identifying novel regulators that provide insights into the underlying processes.
2. Studying the molecular and cellular mechanisms that modify the course of the disease.

Potential Outcomes

This research will lead to the identification of novel therapeutic targets, which may reshape our understanding of how these diseases occur and how we can prevent them. Additionally, it will contribute to the development of novel, individualized treatment strategies.

Translation to Clinical Trials

Finally, we aim to translate our findings to humans to gain initial insights on whether these strategies can be adapted and used in clinical trials. MATRICARD will go beyond technical boundaries and lead to a deep knowledge of ECM-mediated cell-cell communication, revealing its translational potential.