淋巴水肿
卡托普利
医学
纤维化
转化生长因子
淋巴系统
血管紧张素转换酶
血管紧张素II
癌症研究
药理学
内科学
病理
乳腺癌
癌症
受体
血压
作者
Stav Brown,Gabriela D. García Nores,Ananta Sarker,Catherine Ly,Catherine C. Li,Hyeung Ju Park,Geoffrey E. Hespe,Adana Campbell,Raghu P. Kataru,Ömer Aras,Babak J. Mehrara
标识
DOI:10.1016/j.trsl.2023.01.005
摘要
Transforming growth factor-beta 1 (TGF-β1)-mediated tissue fibrosis is an important regulator of lymphatic dysfunction in secondary lymphedema. However, TGF-β1 targeting can cause toxicity and autoimmune complications, limiting clinical utility. Angiotensin II (Ang II) modulates intracellular TGF-β1 signaling, and inhibition of Ang II production using angiotensin-converting enzyme (ACE) inhibitors, such as captopril, has antifibrotic efficacy in some pathological settings. Therefore, we analyzed the expression of ACE and Ang II in clinical lymphedema biopsy specimens from patients with unilateral breast cancer-related lymphedema (BCRL) and mouse models, and found that cutaneous ACE expression is increased in lymphedematous tissues. Furthermore, topical captopril decreases fibrosis, activation of intracellular TGF-β1 signaling pathways, inflammation, and swelling in mouse models of lymphedema. Captopril treatment also improves lymphatic function and immune cell trafficking by increasing collecting lymphatic pumping. Our results show that the renin-angiotensin system in the skin plays an important role in the regulation of fibrosis in lymphedema, and inhibition of this signaling pathway may hold merit for treating lymphedema.
科研通智能强力驱动
Strongly Powered by AbleSci AI