Biomedical subjects
Publications and source records attributed to Sik Lee.
Unilateral renal cystic disease (URCD) is a distinct entity that is one of the renal cystic diseases. The clinical importance of URCD is to make a differential diagnosis from autosomal dominant polycystic kidney disease (ADPKD), multicystic dysplastic kidney, multilocular cystic renal neoplasm, and simple cysts. To confirm the diagnosis and to rule out asynchronous ADPKD requires long-term follow up, especially in younger patients.
BACKGROUND AND AIMS: The Dendroaspis natriuretic peptide (DNP), which was recently isolated from the venom of the green Mamba snake, Dendroaspis angusticeps, is a 38 amino acid peptide containing a 17 amino acid disulfide ring structure. The purpose of this study was to evaluate the effect of haemodialysis (HD) on the plasma concentration of DNP, and to investigate the relationship between the 2-D echocardiographic parameters and the changes in the plasma DNP levels during HD. METHODS: Forty-five haemodialysis patients and 22 healthy individuals underwent a measurement of plasma DNP-like immunoreactivity, serum creatinine, haematocrit, blood pressure and bodyweight before and after each HD session. Echocardiography was performed before and after HD. The peak early diastolic transmitral flow velocity (E), peak late diastolic transmitral flow velocity (A), and E/A ratio were measured by using a pulsed Doppler echocardiogram. RESULTS: The plasma DNP-like immunoreactivity of those in the pre-HD state was significantly higher (235.6 +/- 45.8 pg/mL) than those of the healthy subjects (105.3 +/- 31.1 pg/mL). In addition, the plasma DNP-like immunoreactivity was significantly decreased after HD (204.4 +/- 55.4 pg/mL). The left atrial diameter, left ventricular diameter at end diastole and end systol, E velocity, A velocity, E/A ratio and inferior vena cava diameter were significantly decreased after HD. There were significant correlations between the changes of plasma DNP-like immunoreactivity and the changes in the bodyweight and inferior vena cava diameter, respectively. CONCLUSION: These results suggest that the plasma DNP-like immunoreactivity might be involved in the regulation of the blood volume in patients undergoing HD.
Adrenomedullin (AM) is a multifunctional peptide in human pheochromocytoma. To evaluate whether AM could be an angiogenic factor, we examined its effect on kinases and angiogenic processes. AM induced tyrosine phosphorylation of Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase1/2 (ERK1/2) by using distinct signaling pathways in human umbilical vein endothelial cells (HUVECs). AM also phosphorylated focal adhesion kinase, and phosphatidylinositol 3'-kinase inhibitor inhibited AM-induced focal adhesion kinase phosphorylation. Pretreatment with high concentrations of AM22-52, a putative AM receptor antagonist, partially suppressed AM-induced phosphorylation of Akt, ERK1/2, and focal adhesion kinase. AM and vascular endothelial growth factor produced increases in DNA synthesis and migration in HUVECs. AM induced tube formation in HUVECs, and its effect was inhibited by pretreatment with phosphatidylinositol 3'-kinase inhibitor or ERK1/2 inhibitor. AM induced sprouting in porcine pulmonary arterial endothelial cells and promoted neovessel formation in a mouse Matrigel plug assay. Inhibitors of phosphatidylinositol 3'-kinase and ERK1/2 inhibited AM-induced endothelial sprouting in vitro and angiogenesis in vivo. AM exerts angiogenic activity through activation of Akt, MAPK, and focal adhesion kinase in endothelial cells.
OBJECTIVE: In the initial phase of inflammation, vascular endothelial growth factor (VEGF) can act as a proinflammatory cytokine by inducing adhesion molecules that bind leukocytes to endothelial cells. Adrenomedullin (AM) is known to act as either a proinflammatory or an anti-inflammatory agent. In this study, we examined the effects of AM on adhesion molecule expression and leukocyte adhesiveness in VEGF-stimulated human umbilical vein endothelial cells. METHODS AND RESULTS: When stimulated with VEGF, the mRNAs of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin were dose-dependently upregulated. AM inhibited the VEGF-induced protein and mRNA expression of ICAM-1, VCAM-1, and E-selectin. Phosphatidylinositol 3'-kinase inhibitor and a dominant-negative form of Akt significantly inhibited the suppressive effect of AM on VEGF-induced adhesion molecule expression. Thus, AM inhibits VEGF-stimulated ICAM-1 and VCAM-1 expression through a phosphatidylinositol 3'-kinase/Akt pathway. AM reduced VEGF-induced endothelial adhesiveness for leukocytes. CONCLUSIONS: These results suggest that AM might have an anti-inflammatory role in controlling VEGF-induced adhesion molecule gene expression and adhesiveness toward leukocytes in endothelial cells.
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Mannitol therapy is widely used for reducing brain edema, and ischemic brain swelling. However, mannitol at clinical concentrations induces apoptosis in endothelial cells. Because apoptosis may be a pathogenic mechanism in vascular injury, antiapoptotic agents may have a protective role in mannitol-induced apoptosis. In this study, we examined whether adrenomedullin (AM) prevents mannitol-induced apoptosis and also evaluated the associated signaling pathway of AM in human umbilical vein endothelial cells. AM prevented mannitol-induced apoptosis in a dose-dependent manner. Pretreatment with wortmannin blocked the AM-induced antiapoptotic effect. AM stimulated Akt at Ser473, and wortmannin inhibited the AM-induced Akt phosphorylation. These findings indicate that phosphatidylinositol 3'-kinase/Akt pathway transmits the survival signal from AM. The potency of antiapoptotic effect of AM is stronger than that of vascular endothelial growth factor and angiopoietin-1 in mannitol-induced apoptosis. AM can have a protective role not only in umbilical vein, but also in pulmonary, coronary, and aortic endothelial cells. These findings indicate that AM has a potent protective role in mannitol-induced apoptosis, through phosphatidylinositol 3'-kinase/Akt pathway. Therefore, pretreatment with AM might help to maintain normal endothelial integrity during systemic mannitol therapy.
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