Contrast MR lymphangiography with gadobenate dimeglumine is capable of visualizing the precise anatomy of lymphatic vessels and lymph nodes in lymphedematous limbs. It also provides information concerning the functional status of lymph flow transport in the lymphatic vessels and lymph nodes of these limbs.
Angiopoietin (Ang)-2, a ligand of the receptor tyrosine kinase Tie2, is known to be involved in the regulation of embryonic lymphangiogenesis. However, the role of Ang-2 in postnatal pathological lymphangiogenesis, such as inflammation, is largely unknown. We used a combination of imaging, molecular, and cellular approaches to investigate whether Ang-2 is involved in inflammatory lymphangiogenesis. We observed strong and continuous expression of Ang-2 on newly generated lymphatic vessels for 2 wk in sutured corneas of BALB/c mice. This expression was concurrent with an increased number of lymphatic vessels. TNF-α expression also increased, with peak TNF-α expression occurring before peak Ang-2 expression was reached. In vitro experiments showed that TNF-α stimulates Ang-2 and Tie2 and ICAM-1 expression on human lymphatic endothelial cells (LECs) and blood vascular endothelial cells (BECs). Ang-2 alone did not affect the biological behavior of LECs, whereas Ang-2 combined with TNF-α significantly promoted the proliferation of LECs but not BECs. In mouse models, blockade of Ang-2 with L1-10, an Ang-2-specific inhibitor, significantly inhibited lymphangiogenesis but promoted angiogenesis. These results clearly indicate that Ang-2 acts as a crucial regulator of inflammatory lymphangiogenesis by sensitizing the lymphatic vasculature to inflammatory stimuli, thereby directly promoting lymphangiogenesis. The involvement of Ang-2 in inflammatory lymphangiogenesis provides a strong rationale for the exploitation of anti-Ang-2 treatment in the prevention and treatment of tumor metastasis and transplant rejection.
Background?Imaging of the lymphatic system is difficult because of its structural and anatomical characteristics, and the conventional diagnostic method, radionuclide-based imaging, has the disadvantage of poor resolution. Magnetic resonance (MR) imaging has been shown the capability of depicting lymphatic channels in lymphedema recently. The purpose of this study was to evaluate the imaging of MR lymphangiography (MRL) in diagnosis of limb lymphedema and its possible role in the microsurgical management of lymphedema.
Methods?A total of 710 patients with primary lymphedema (n?=?378), secondary lymphedema (n?=?332), were enrolled in the study. Contrast-enhanced lymphangiography was performed with 3.0 T MR unit (Philips Medical Systems, Best, The Netherlands) after intracutaneously injection of gadobenate dimeglumine. Kinetic of enhanced lymph flow within lymphatics and lymph nodes as well as the morphological abnormalities of lymphatic system were evaluated.
Results?MRL was able to display the detailed anatomical changes in the vessels and nodes. In primary lymphedema, there are three major types of lymphatic system malformation: (1) only lymph nodes affected, (2) only lymph vessels affected, and (3) both lymph vessels and lymph nodes affected. In secondary lymphedema MRL clearly demonstrated tortuous and dilated collecting lymphatics in lymphedemtous limbs. MRL also provided information concerning the functional status of lymph transport in lymphatic vessels and nodes by real-time visualization of enhanced lymph flow in lymphatic channels and within lymph nodes.
Conclusion?Contrast MRL was capable of evaluating the anatomical and functional status of lymphatic vessels and lymph nodes in lymphedematous limb. This new imaging shows good potential for use in the diagnosis and surgical management of lymphedema.
The number of functional remaining lymphatic collectors increases with the prolongation and severity of BCRL. This may imply persistent reactions of lymphatic collectors in response to lymphostasis.
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