Edn1, which encodes endothelin 1, a potent endogenous vasoconstrictor, plays a crucial role in maintaining vascular homeostasis and redistributing tissue blood flow during exercise [3]. It is involved in multiple biological pathways, and its abnormal regulation has been linked to various diseases, making it an important gene for understanding physiological and pathological processes. Genetic models, such as gene knockout mouse models, can help further clarify its functions.

Edn1 has been associated with numerous diseases. A meta-analysis found that the EDN1 rs5370 polymorphism was significantly associated with an increased risk of pulmonary arterial hypertension (PAH) in all genetic models [1]. In colorectal cancer, a positive correlation between EDN1 and its receptor EDNRA levels was found, and both EDN1 and EDNRA promoted cell proliferation and migration in vitro, with the EDN1/EDNRA/β -arrestin axis regulating STAT3 phosphorylation to drive cancer progression [2]. The EDN1 rs5370 T allele was more prevalent in high-altitude pulmonary oedema (HAPE) patients, and was associated with elevated EDN1 gene expression and ET-1 levels, indicating its role in adaptation/maladaptation physiology under hypobaric hypoxia [3]. Additionally, the EDN1 gene polymorphism rs5370 was correlated with an increased risk of preeclampsia, especially severe and early-onset forms [4]. It may also be involved in acute mountain sickness, as the allele T in SNP rs2070699 was positively correlated with its occurrence [6]. In non-small cell lung cancer, EDN1 promoted cisplatin resistance by regulating the TNF signaling pathway [5], and in hepatocellular carcinoma, the ARHGEF2/EDN1 pathway participated in ER stress-related drug resistance by promoting angiogenesis and malignant proliferation [7].

In conclusion, Edn1 is essential for maintaining vascular homeostasis. Model-based research, especially studies on its polymorphisms, has revealed its significant role in multiple disease areas, including pulmonary arterial hypertension, colorectal cancer, high-altitude-related disorders, preeclampsia, non-small cell lung cancer, and hepatocellular carcinoma. Understanding Edn1 functions through these models provides insights into disease mechanisms and potential therapeutic targets.