Lymphatic network in atherosclerosis: the underestimated path

Abstract

The lymphatic system is a key component of tissue fluid homeostasis. In contrast to the closed and high-pressure blood vascular system, the lymphatic vascular system transports lymph in an open and low-pressure network. A prerequisite player in the transport of immune cells and cholesterol metabolism, it has been understudied until recently. Whereas defects in lymph circulation are mostly associated with pathologies such as congenital or acquired lymphedema, emerging significant developments are unraveling the role of lymphatic vessels in other pathological settings. In the last decade, discoveries of underlying genes responsible for developmental and postnatal lymphatic growth, combined with state-of-the-art lymphatic function imaging and quantification techniques, have matched the growing interest in understanding the role of the lymphatic system in atherosclerosis. With a historical perspective, this review highlights the current knowledge regarding interaction between the lymphatic vascular tree and atherosclerosis, with an emphasis on the physiological mechanisms of this multifaceted system throughout disease onset and progression.

Abstract

The blood and lymphatic vascular systems are parallel but interdependent networks. The lymphatic system governs the transport of superfluous interstitial fluids from peripheral tissues to the blood circulation, maintaining fluid balance throughout the body. Defects in lymphatic function have been broadly associated with pathologies such as congenital or acquired lymphedema. Although longstanding observations suggested that the lymphatic vasculature could be central in the development of chronic inflammatory diseases, recent publications specifically point out its potential implication in atherosclerosis. In this review, we highlight the current knowledge unraveling the interaction between the lymphatic network and atherosclerosis, with an emphasis on the physiological mechanisms of this intricate system.