Grant: Project Grant

High blood cholesterol is an important risk factor of cardiovascular disease such as atherosclerosis. High-density lipoprotein (HDL) is called ''good cholesterol'' because it transports cholesterol away from tissues, such as the blood vessel walls, carrying cholesterol through the blood circulation for eventual excretion into intestines. Unfortunately, the clinical outcomes aiming at increasing levels of circulating HDL (or "good cholesterol") have not been as successful as expected, suggesting that raising HDL may not lead to an increased cholesterol clearance capacity or prevention of coronary heart disease. Expressed differently, more cargo ships (cholesterol transporter) leaving from the harbour docks (blood vessel wall), have not led to more merchandise 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 (Martel, JCI 2013). 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, accordingly, peripheral lymph contains cholesterol transporters (HDL), a role in cholesterol transport seemed logical. Therefore, we view that improvement of the delivery efficiency would rely on enhancing the navigation conditions, instead of the number of cargo ships per se. The main objective of our emerging research team aims to understand the mechanisms connecting abnormal lymphatic function and atherosclerosis progression, to ultimately lead to the identification of new therapeutic targets.