An early sign of cardiovascular disease
Cardiovascular diseases are a serious and increasing threat to human health worldwide. Endothelial dysfunction, a malfunction of the inner surface of blood vessels, is one of the earliest indicators, but also a key causal factor of cardiovascular disease.

This project aims to develop drugs that can prevent organ damage caused by endothelial dysfunction. The focus will be on identifying new targets and mechanisms underlying different aspects of endothelial dysfunction. So far experiments have shown that a new target for drugs is indeed capable of preventing organ, in this case kidney, damage. In addition, new possible targets have been identified in the form of signal molecules. Further research will focus on preventing production of these molecules as well as preventing their influence on cells. The research may make a significant scientific and therapeutic contribution to this major medical field.

Fast facts
Full project title: Metalloproteases and novel targets in endothelial dysfunction
Start date: February 2007
End date: February 2012
Goal: Beneficially modulate basic mechanisms underlying different aspects of endothelial dysfunction and identify new relevant targets and mechanisms
Principal investigator: Jo de Mey
Project size: 8 FTE's
Partners: Abbott, Academic Medical Center (AMC) Amsterdam, Leiden University Medical Center, Maastricht University, VU University Medical Center 


The endothelium is the lining of the inner surface of blood vessels and consists of a small layer of cells. It serves as an interface between the blood vessels and the blood, and allows blood to flow smoothly. It is not only a lining, however, it also is one of the largest secreting organs in the body. It is involved in the regulation of homeostasis, the maintenance of a stable internal environment. As such it is involved in blood pressure, inflammatory processes and clot-forming of blood (coagulation). In case of malfunctioning the endothelial cells fail to perform homeostatic functions such as regulating blood flow and keeping blood fluid, and less molecules that protect the blood vessels are secreted. Instead, substances that promote plaque formation are produced. The stimulus that would normally cause vessels to expand and therewith increase the blood flow fail to do so. Moreover, they may even cause contractions. As such patients experience chest pain. In general, the disease is considered to be one of the earliest, clinically detectable, signs of heart disease. If properly treated the disease is reversible.   

PhD theses from this project

“TI Pharma's program managers are experts in the content, enabling them to keep parties focused on the goals that were agreed upon at the outset.”

Jan Raaijmakers
Past VP External Scientific Collaborations GSK Europe
Chair TI Pharma Board of Directors

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