Organotypic angiogenesis, lymphangiogenesis and vascular remodeling

Abstract

Part I. Conditional ablation of LYVE-1+ cells unveils defensive roles of lymphatic vessels in intestine and lymph node To understand more about the potential organotypic role and vulnerability of lymphatic vessels (LVs), I generated a LYVE-1-Cre/iDTR (LCiDT) double-transgenic mouse and ablated LYVE-1-expressing LVs in adult mice in a diphtheria toxin (DT)-inducible manner based on selective expression of LYVE-1 in most LVs. Strikingly, LVs in the small intestine and lymph nodes (LNs) were rapidly ablated, but LVs in the other organs were relatively intact at 24 h after DT administration. Unexpectedly, LCiDT mice died from septic shock without visible edema at 24 and 60 h after DT administration. The cause of death appeared to be related to acute failure of immune surveillance systems in the small intestine and draining LNs. Of note, acute loss of lymphatic lacteals in intestinal villi appeared to trigger distortion of blood capillaries and whole architecture of the villi whereas acute loss of LVs in LNs caused dysfunction of lymph drainage and abnormal distribution of dendritic cells and macrophages. Thus, intact LVs are required for structural and functional maintenance of surrounding tissues in an organotypic manner, at least in the intestine and LNs.

Part II. Vasculatures of endocrine organs are dynamically remodeled under hormonal stimulation and regulated by distinct vascular growth factor-receptor interaction Endocrine glands are generally highly vascularized organs required for active hormonal regulation. The endocrine vasculature has distinguishable characteristics such as endothelial fenestrations, and it also serves as a conduit between endocrine gland blood vessels and systemic circulation. Here, I show unique patterns of gene expressions for angiogenic growth factors and distinctive features of vascular remodeling upon various stimuli in the thyroid gland, parathyroid gland and adrenal glands. Interestingly, thyroid gland vasculatures were most d...