Topical captopril: a promising treatment for secondary lymphedema

被引：11

作者：

Brown, Stav ^{[1
]}

Nores, Gabriela D. G. ^{[1
]}

Sarker, Ananta ^{[1
]}

Ly, Catherine ^{[1
]}

Li, Catherine C. ^{[1
]}

Gardenier, Jason ^{[1
]}

Hespe, Geoffrey E. ^{[1
]}

Brown, Tal ^{[1
]}

Park, Hyeung Ju ^{[1
]}

Campbell, Adana ^{[1
]}

Shin, Jinyeon ^{[1
]}

Kataru, Raghu P. ^{[1
]}

Aras, Omer ^{[1
]}

Dayan, Joseph H. ^{[1
]}

Mehrara, Babak J. ^{[1
,2
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Surg Plast & Reconstruct Surg Serv, New York, NY USA

[2] Mem Sloan Kettering Canc Ctr, Dept Surg Plast & Reconstruct Surg Serv, 328 East 62nd St, New York, NY 10065 USA

来源：

TRANSLATIONAL RESEARCH | 2023年 / 257卷

关键词：

ANGIOTENSIN-CONVERTING-ENZYME; GROWTH-FACTOR-BETA; LYMPHATIC REGENERATION; CONTRACTILE ACTIVITY; RECEPTOR ANTAGONIST; TISSUE FIBROSIS; RENAL FIBROSIS; LIVER FIBROSIS; ACE-INHIBITORS; TGF-BETA;

D O I：

10.1016/j.trsl.2023.01.005

中图分类号：

R446 [实验室诊断]; R-33 [实验医学、医学实验];

学科分类号：

1001 ;

摘要：

Transforming growth factor-beta 1 (TGF-/1)-mediated tissue fibrosis is an important regulator of lymphatic dys-function in secondary lymphedema. However, TGF-/1 targeting can cause toxicity and autoimmune complica-tions, limiting clinical utility. Angiotensin II (Ang II) modulates intracellular TGF-/1 signaling, and inhibition of Ang II production using angiotensin-converting enzyme (ACE) inhibitors, such as captopril, has antifibrotic effi-cacy in some pathological settings. Therefore, we analyzed the expression of ACE and Ang II in clinical lymph-edema 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-/1 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.

引用

页码：43 / 53

页数：11

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