Grant: Project Grant - PA: Circulatory and Respiratory Health

High blood cholesterol is an important risk factor of cardiovascular disease (CVD) such as atherosclerosis. High-density lipoprotein (HDL) is called ''good cholesterol''. HDL transports cholesterol away from tissues like the blood vessel walls and carries cholesterol through the blood circulation for eventual excretion into the intestines. Unfortunately, the clinical outcomes aiming at increasing levels of circulating HDL ("good cholesterol") have not been as successful as expected. This suggests that raising HDL may not lead to an increased cholesterol clearance capacity or prevention of CVD. In essence, we can make a similar comparison with cargo ships. For example, despite more cargo ships (HDL) leaving from the harbour docks (blood vessel wall) has not led to more merchandise being delivered (cholesterol clearance). Thus, a better understanding of the cholesterol clearance process has become necessary to efficiently modulate the progression of atherosclerosis. In this regard, we provided unprecedented insight into the path that cholesterol trapped in peripheral tissues takes during cholesterol mobilization for eventual excretion. We demonstrated that cholesterol (merchandise) gets out of tissues (harbour docks) and reaches the bloodstream (sea) by first entering so-called lymphatic vessels (canals). As the lymphatic system - lymph, from Latin lympha, meaning water - generally governs the transport of macromolecules from the tissues to the blood and peripheral lymph contains cholesterol transporters (HDL), a role in cholesterol transport seemed logical. Therefore, we view that improving the delivery efficiency would rely on enhancing the navigation conditions, instead of the number of cargo ships. The main objective of our translational research program aims to understand the mechanisms connecting abnormal lymphatic function and atherosclerosis onset and progression, which may ultimately lead to the identification of new therapeutic targets in CVD.