Biomechanics and signaling in models of congenital heart valve defects

Projektinformationen

EVALVE

ID Finanzhilfevereinbarung: 682938

DOI

10.3030/682938

Projekt abgeschlossen

EK-Unterschriftsdatum 25 November 2016

Startdatum 1 Dezember 2016

Enddatum 31 Mai 2024

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten

€ 2 000 000,00

EU-Beitrag

€ 2 000 000,00

Koordiniert durch

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
United Kingdom

Periodic Reporting for period 5 - EVALVE (Biomechanics and signaling in models of congenital heart valve defects)

Berichtszeitraum: 2022-09-01 bis 2024-05-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Cardiovascular diseases (CVDs) are a major global health issue. Abnormal blood flow contributes to CVDs, and understanding how mechanical forces affect the heart is crucial. Understanding how mechanical forces impact heart valve development is vital for preventing CVDs. Heart valve defects are common, and their causes are often linked to genetic and mechanical factors.

This research aims to:

Measure the mechanical forces on the heart during development
Identify how heart cells sense and respond to these forces
Understand how these forces influence heart valve formation and function

We combined biology, physics, and computer modeling to study heart development in zebrafish. By examining how heart cells behave under different conditions, we hope to uncover new ways to prevent and treat heart valve problems.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

Objective 1: Quantifying Mechanical Forces and Valve Defects

We have developed a new method to measure the forces acting on heart cells during the heartbeat. By tracking individual heart cells and creating a detailed 3D model of the heart, we can calculate blood flow pressure and the forces between cells. This information will help us understand how abnormal heart function (cardiomyopathy) affects the forces on heart valves and contributes to valve defects.
Objective 2: Identifying Key Proteins for Mechanotransduction

Our research has identified several proteins involved in sensing and responding to mechanical forces within heart cells. These proteins, including Piezo and TRP channels, play a crucial role in heart valve development. We have shown that these proteins work together with other factors (Yap1, Klf2, Notch) to control gene activity and cell behavior.
Objective 3: Understanding Mechanotransduction in Valve Formation

We have investigated how heart cells behave during valve development, focusing on the changes that occur before and after valve tissue formation. Our findings indicate that mechanical forces, working together with specific proteins and cellular processes, are essential for normal valve development. Disruptions in these processes can lead to valve defects.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

Project Overview

The primary objective of this project is to elucidate the role of mechanical forces in shaping the cardiovascular system. Our focus is on understanding how these forces influence heart development, particularly valve formation and cell behavior.

Key Achievements

Identified the critical role of mechanical forces in heart valve development: We have demonstrated that blood flow exerts significant influence on valve formation, with specific proteins acting as mechanosensors.
Uncovered the importance of cell behavior in tissue morphogenesis: Our research has shown that changes in cell shape and size, influenced by mechanical forces, are crucial for heart development.
Established a link between cilia and heart development: We have identified cilia as key signaling organelles in the heart and established their connection to heart defects.
Developed advanced imaging techniques: We have created innovative methods to track and analyze heart cell behavior in 3D, providing valuable insights into heart function.

Current Status and Next Steps

We have made significant progress in understanding the complex interplay between mechanical forces, cell behavior, and genetic factors in cardiovascular development. Our next steps include:

Deepening our investigation into the specific molecular mechanisms underlying mechanotransduction in heart cells.
Expanding our research to other cardiovascular structures, such as blood vessels.
Developing therapeutic strategies based on our findings to address heart conditions.

Overall, the project is progressing well, and we are optimistic about the potential impact of our research on the field of cardiovascular biology.

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