Pathophysiology of Lymphatic Circulation in Different Disease Conditions

Lymphatic vessels have historically been viewed as passive conduits for fluid and as a transit system of immune cells from the extracellular space to the blood circulation. This classical perspective is increasingly being reappraised as new functions of lymphatic vessels are being revealed. Lymphatic vessels within different organs and in different physiological and pathological processes show a remarkable heterogeneity, reflecting their functional specialization. The discovery of lymphatic vessels in organs where they were previously not thought to exist has opened new avenues of investigation for unexpected roles. The cardinal manifestation of lymphatic dysfunction is lymphedema; emerging evidence shows that lymphatic dysfunction takes an active part in the uptake and clearance of cholesterol from peripheral tissues and atherosclerotic lesions. It has also been speculated that by enhancing lymphangiogenesis it might be possible to develop novel therapeutic modalities to modulate inflammatory responses of metabolic and cardiovascular diseases. By contrast, reducing lymphangiogenesis might constitute a novel approach to prevent cancer metastasis. The identification of novel regulators of the lymphatic vasculature and the development of suitable animal models to explore the pathophysiology of lymphatic circulation are providing new information toward the development of novel molecular mechanisms that could facilitate the design of therapeutic strategies against cancer, inflammatory conditions, and cardiovascular diseases.