An ex vivo model to test new potential treatments for atherosclerosis

Lasse Gøbel Lorentzen

Atherosclerosis is a commonly occurring condition where the vessel wall is thickened by accumulated biological material, called plaque. These plaques are very diverse, and the state of disease can vary enormously. While some plaques are stable and remain symptom-free for years, others are unstable and can suddenly rupture and form blood clots. This may lead to serious complications such as heart attack and stroke.

The mechanisms that lead to plaque instability are sparsely elucidated and there is a critical lack of treatments that can affect the stability of atherosclerotic plaques. A key reason is that commonly used animal models of atherosclerosis do not develop unstable plaques or blood clots in the heart and brain. Thus, there is a lack of a model that accurately reflects the disease mechanisms that make atherosclerosis a critical condition in humans.

To relieve symptoms or avoid serious complications, atherosclerotic, plaques are routinely removed during surgical procedures. These plaques are normally discarded, but we will instead collect and culture these plaques, i.e, store plaques under close to physiological conditions. We believe that cultured plaques could be a useful model for testing potential novel drugs – particularly treatments targeting plaque stability. To test this, cultured plaques will be subjected to a number of different treatments aimed at increasing plaque stability. We will use a combination of histological methods and proteome analysis to evaluate the effects of these treatments. This may form the basis for further development of drugs that can stabilize atherosclerotic plaques and prevent serious complications in patients with cardiovascular disease.

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