Transcription Factor Control of Lymphatic Quiescence and Maturation of Lymphatic Neovessels in Development and Physiology

Abstract

The lymphatic system is a vascular system comprising modified lymphatic endothelial cells, lymph nodes and other lymphoid organs. The system has diverse, but critical functions in both physiology and pathology, and forms an interface between the blood vascular and immune system. It is increasingly evident that remodelling of the lymphatic system occurs alongside remodelling of the blood microvascular system, which is now considered a hallmark of most pathological conditions as well as being critical for normal development. Much attention has focussed on how the blood endothelium undergoes phenotypic switching in development and disease, resulting in over two decades of research to probe the mechanisms underlying the resulting heterogeneity. The lymphatic system has received less attention, and consequently there are fewer descriptions of functional and molecular heterogeneity, but differential transcription factor activity is likely an important control mechanism. Here we introduce and discuss significant transcription factors of relevance to coordinating cellular responses during lymphatic remodelling as the lymphatic endothelium dynamically changes from quiescence to actively remodelling.

Mechanisms of Myocardial Edema Development in CVD Pathophysiology

“…Lymphatic vessels are involved in the transport of excess fluid from the interstitium, but for interstitial drainage and lymph transport the normal pumping function of the heart within certain limits is required [17], since small lymphatic capillaries do not have contractile cells [18,19]. In order to push lymph, the pressure created by cardiomyocytes during systole is necessary [20,21]. Hence, pulsating shocks of blood pressure into the capillaries can lead to the penetration of fluid into the interstitial space under normal conditions.…”

Molecular and metabolic orchestration of the lymphatic vasculature in physiology and pathology

“…This regulation encompasses not only its establishment and maturation but also the maintenance of lymphatic identity and function in postnatal stages. Albeit less explored than angiogenesis, the molecular network coordinating lymphangiogenesis has been extensively studied over the last decades 6 , 9 – 12 . Different molecular players, including transcription factors, growth factors, and cytokines, have been described as key mediators of embryonic and adult lymphangiogenesis.…”

“…So far, the molecular regulation of lymphangiogenesis has been extensively studied and reviewed, from the transcriptional control of lymphatic fate acquisition in embryonic stages to the growth factors and signaling pathways controlling developmental and adult lymphangiogenesis 6 , 9 – 12 . In the last decade, an involvement of metabolism in lymphatic formation and function has been elucidated.…”