Cdh5, also known as VE-cadherin, is a cadherin expressed by endothelial cells. It is crucial for vascular morphogenesis, maintaining vascular integrity and lymphatic function. It may be involved in pathways such as the cGAS-STING pathway in endothelial cells [2]. Cdh5 is of great biological importance as it plays a role in processes like the development of the lymphatic vasculature, and its abnormal expression is associated with diseases such as lymphedema and various cancers [1,3]. Genetic models, especially knockout (KO) and conditional knockout (CKO) mouse models, are valuable for studying Cdh5.

In a study on lymphedema, six different variants (five missense and one nonsense) were detected in the Cdh5 gene in Italian patients with lymphedema, suggesting that Cdh5 variants may contribute to the onset of lymphedema, although further in-vitro studies are needed [1]. In a doxorubicin-induced cardiotoxicity study, EC-specific conditional Sting deficiency (Stingflox/flox/Cdh5-CreERT) mice were used. It was found that the cGAS-STING pathway in cardiac ECs plays a critical role in doxorubicin-induced cardiotoxicity, and EC-specific Sting deficiency significantly prevented cardiotoxicity and endothelial dysfunction [2]. In an ischemic stroke study, using VE-cadherin-Cre transgenic mice to conditionally delete Fpn1 in mouse endothelial cells, it was shown that Fpn1 knockout in ECs had a dual consequence: neuroprotective during the acute phase but inhibitory during the recovery phase of ischemic stroke [4].

In conclusion, Cdh5 is essential for vascular and lymphatic-related biological functions. Studies using KO/CKO mouse models have revealed its roles in lymphedema, doxorubicin-induced cardiotoxicity, and ischemic stroke. These findings contribute to our understanding of the underlying mechanisms of these diseases and may potentially lead to new therapeutic strategies.