Young Jun Koh

Conditional ablation of LYVE-1+ cells unveils defensive roles of lymphatic vessels in intestine and lymph nodes.

To unveil the organotypic role and vulnerability of lymphatic vessels, we generated a lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)-Cre/iDTR double-transgenic mouse and ablated LYVE-1-expressing lymphatic vessels in adult mice in a diphtheria toxin (DT)-inducible manner based on selective expression of LYVE-1 in most lymphatic vessels. Strikingly, lymphatic vessels in the small intestine and lymph nodes were rapidly ablated, but lymphatic vessels in the other organs were relatively intact at 24 hours after DT administration. Unexpectedly, LYVE-1-Cre/iDTR mice died of sepsis without visible edema at 24 and 60 hours after DT administration. The cause of death appeared to be related to acute failure of immune surveillance systems in the small intestine and draining lymph nodes. Of note, acute loss of lymphatic lacteals in intestinal villi appeared to trigger distortion of blood capillaries and the whole architecture of the villi, whereas acute loss of lymphatic vessels in lymph nodes caused dysfunction of lymph drainage and abnormal distribution of dendritic cells and macrophages. Thus, intact lymphatic vessels are required for structural and functional maintenance of surrounding tissues in an organotypic manner, at least in the intestine and lymph nodes.

Endothelial Deletion of Phospholipase D2 Reduces Hypoxic Response and Pathological Angiogenesis

Objective— Aberrant regulation of the proliferation, survival, and migration of endothelial cells (ECs) is closely related to the abnormal angiogenesis that occurs in hypoxia-induced pathological situations, such as cancer and vascular retinopathy. Hypoxic conditions and the subsequent upregulation of hypoxia-inducible factor-1&agr; and target genes are important for the angiogenic functions of ECs. Phospholipase D2 (PLD2) is a crucial signaling mediator that stimulates the production of the second messenger phosphatidic acid. PLD2 is involved in various cellular functions; however, its specific roles in ECs under hypoxia and in vivo angiogenesis remain unclear. In the present study, we investigated the potential roles of PLD2 in ECs under hypoxia and in hypoxia-induced pathological angiogenesis in vivo. Approach and Results— Pld2 knockout ECs exhibited decreased hypoxia-induced cellular responses in survival, migration, and thus vessel sprouting. Analysis of hypoxia-induced gene expression revealed that PLD2 deficiency disrupted the upregulation of hypoxia-inducible factor-1&agr; target genes, including VEGF, PFKFB3, HMOX-1, and NTRK2. Consistent with this, PLD2 contributed to hypoxia-induced hypoxia-inducible factor-1&agr; expression at the translational level. The roles of PLD2 in hypoxia-induced in vivo pathological angiogenesis were assessed using oxygen-induced retinopathy and tumor implantation models in endothelial-specific Pld2 knockout mice. Pld2 endothelial-specific knockout retinae showed decreased neovascular tuft formation, despite a larger avascular region. Tumor growth and tumor blood vessel formation were also reduced in Pld2 endothelial-specific knockout mice. Conclusions— Our findings demonstrate a novel role for endothelial PLD2 in the survival and migration of ECs under hypoxia via the expression of hypoxia-inducible factor-1&agr; and in pathological retinal angiogenesis and tumor angiogenesis in vivo.

Wrist-wearable bioelectrical impedance analyzer with contact resistance compensation function

Bioelectrical impedance analysis (BIA) is used to calculate the body fat percentage of a human by applying a small amount of alternating current through a human body and measuring the impedance. As the electrode size of a BIA device becomes small, the measurement error of impedance becomes large due to the contact resistance between the electrode and human skin. Most commercial BIA devices, therefore, utilize electrodes large enough to ignore the effect of contact resistance, e.g. 35×40 mm2 × 4EA. We propose a novel method for compensating the contact resistance by performing a 4-point and a 2-point measurement alternately such that body impedance can be accurately estimated even with a considerably smaller size of electrode (8×8 mm2 × 4EA). Also, we report a wrist-wearable BIA device with single-finger contact measurement and analysis results of user data acquired from 148 volunteers: the correlation coefficient of body fat percentage was 0.903 and the SEE (Standard Error of Estimate) of body fat percentage was 3.07% when compared with InBody 720 (whole-body composition analyzer), which was found to be at the same level of performance as commercial portable upper-body BIA device.