Lymphangiogenesis in renal diseases

Abstract

Lymphatic vessels (LVs) are thin walled structures that transport lymph from tissues to lymph nodes. By this function they are complementary to the cardiovascular system in the maintenance of body fluid homeostasis. They play a pivotal role in many (patho)-physiological processes, such as inflammation, immune surveillance and tolerance, fat abortion and metabolism, and general tissue homeostasis, and are involved in disease conditions as diverse as hypertension, atherosclerosis, transplant rejection and survival, and tumor metastasis. Although our understanding has been improved substantially, the biology of LVs is still in its infancy. During recent years many details have emerged as to how LVs function in diseased states, mostly in cancer related conditions. However, the functional significance of the lymphatic network in individual organ health and disease is still poorly understood. Data obtained in kidney transplantation, albeit few, support the important role of LV in intra-organ pathophysiology. Lymphangiogenesis, the outgrowth of preexisting and genesis of new LVs, is an important component of the tissue response to microenvironmental changes, and can have huge impact on disease progression and tissue homeostasis. In the present thesis, we have provided more insight into the mechanistical role of lymphatic vessels (LVs) and lymphangiogenesis in the pathophysiology of renal diseases. To this end, we evaluated whether lymphangiogenesis occurs in renal disease conditions, and if so, whether lymphangiogenesis associates with the degree of renal damage. Even more important, we studied whether targeting lymphangiogenesis can pose a beneficial therapeutic effect in experimental models of kidney injury