New ways to tackle cardiovascular diseases
Atherosclerotic cardiovascular disease (CVD) is the leading cause of mortality worldwide. Current therapeutic treatments are primarily based on the use of statins and aimed at decreasing cholesterol levels.

Despite their proven effectiveness and widespread use, the incidence of CVD remains high, implying that there is an urgent need for additional therapeutic strategies. Recent work has provided evidence that certain proteins in cells, called nuclear, receptors playan important role in controlling causes of CVD. These are, therefore, potential therapeutic targets for treatment and prevention of CVD. This project aims to understand the mechanisms by which these receptors act. The receptors influence many different physiological processes. Modulating them currently means the desired result is usually achieved, but with many side effects. Understanding their mechanism may lead to a more accurate modulation, thus reducing or eliminating side effects. Research so far has yielded, among other findings, a method to completely map the influence of potential new drugs on the glucocorticoid receptor. This receptor not only plays a role in the development of CVD, but is also involved in immune response, metabolism and development.

Fast facts
Full project title: Nuclear receptors as targets for anti-atherosclerotic therapies
Start date: June 2007End date: June 2011
Goal: Identifying potential therapeutic targets for treatment and prevention of cardiovascular disease and developing methods to improve modulation of these targets
Principal investigator: Martin-Jan Smit, MSD
Project size: 6,4 M
Partners: Academic Medical Center Amsterdam, Leiden University, MSD, Radboud University Nijmegen, University Medical Center Groningen


Atherosclerosis is a condition in which plaque, caused by fatty materials such as cholesterol, builds up inside your arteries. The plaque narrows the arteries and limits the flow of blood, which contains oxygen, to the organs. Moreover, as a result of the plaque the walls of the arteries exhibit a chronic inflammatory reaction. The exact cause of artherosclerosis is unknown. There are, however, certain known risk factors, such as limited excercise, smoking and an unhealthy diet. Generally symptoms are only exposed in a very late stage, where a sudden heart attack is the first sign.

In most western countries atherosclerosis is the main cause of disease and death. In the Netherlands it accounts for 35.000 deaths each year. This is twice the amount of deaths caused by cancer.

PhD theses from this project

Zhaosha Li (project T2-110-1)
Intervention in Hepatic Lipid Metabolism

“What TI Pharma can deliver from collaborations is more efficient healthcare, faster time to market and quicker patient benefit.”

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