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.

Cell Types Involved

There is a plethora of cell types involved in these conditions, 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 Studies and ECM Proteins

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

• Silencing of inflammatory functions
• Modulation of ECM composition

The ECM hence not only represents a meshwork in which cells are organized but also serves as a communication hub to transduce 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.

Expected Outcomes

This research will lead to the identification of novel therapeutic targets, which might 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.