On October 25, 2021, the article of the team of Professor Wang Jian with SKLRD, “Resolvin E1 Attenuates Pulmonary Hypertension by Suppressing Wnt7a/β-Catenin Signaling”, was published online in Hypertension, the academic journal of American Heart Association. Adopting the model of pulmonary arterial hypertension of Guinea pigs induced by a low level of oxygen, the research discovered for the first time that Resolvin E1 could reduce the cell proliferation at the smooth muscle of pulmonary artery and attenuate pulmonary hypertension by suppressing the Wnt7a/β-Catenin signaling.

Pulmonary hypertension (PH) is a malignant pulmonary blood vessel disease characterized by the constant rising of pulmonary arterial tension and resistance. It has been called a “cancer” amongst the cardiovascular diseases due to its characteristics such as the difficulty to be diagnosed in the early stage, the poor natural prognosis effect and the short life cycle. According to the latest epidemiological data, the low-oxygen PH, namely PH related with respiratory system diseases and low oxygen, keeps increasing from year to year, which has become a major type of diseases that seriously endanger the people’s health. The thickening of pulmonary vascular wall induced by the excessive proliferation of smooth muscle cells of pulmonary small vessels is the most important pathological process of low oxygen induced PH. Therefore, it can provide us with new targets for the treatment of PH by studying the new mechanism of how to suppress the smooth muscle cell proliferation at the pulmonary artery.

According to the latest research, Resolvin E1 (RvE1) from ω -3 polyunsaturated fatty acid (PUFA) not only acts on inflammatory cells and unleashes its anti-inflammatory effect widely, but also affects the function of non-inflammatory cells-- smooth muscle. By dying the lung slices of PH patients, the research team of Wang Jian discovered that the expression quantity of ChemR23, the receptor of RvE1, in the pulmonary arterial smooth muscle declined. Through an animal experiment, they discovered that RvE1 had a therapeutic effect on PH through the receptor ChemR23 and could improve the hemodynamic index of Guinea pigs with PH induced by low oxygen, suppress pulmonary vascular remodeling and improve their right ventricular function. By studying the mechanism, they discovered that the RvE1/ChemR23 signal axis, by reducing the activity of PKA, could reduce the phosphorylation level of serine, the 349th point of the transcription factor Egr2 (namely transcriptional activity), thereby reducing the expression of Wnt7a and ultimately reducing the cell proliferation at the smooth muscle of pulmonary artery. Later, the research team used the model of inducing PH in the Guinea pigs with monocrotaline and gave the treatment of RvE1(10μg/Kg, intraperitoneal injection), discovering that RvE1 can obviously attenuate pulmonary vascular remodeling caused by the cell proliferation at the pulmonary arterial smooth muscle induced by monocrotaline. The research has provided a theoretical basis for RvE1 to be used in the clinical treatment of pulmonary arterial hypertension patients.

Fig. Resolvin E1/ChemR23 signal axis regulates the cell proliferation at pulmonary arterial smooth muscle

Liu Guizhu, a SKLRD post-doctor, Wan Naifu, a doctoral candidate with Ruijin Hospital of Shanghai Jiaotong University, Liu Qian, a doctoral candidate of Tianjin Medical University are the first co-authors; Professor Wang Jian, Professors Shen Yujun and Yu Ying of Tianjin Medical University are corresponding authors; the SKLRD and Guangzhou Medical University are the correspondence units of the paper. The research has been funded by National Natural Science Foundation of China and National Key R&D Program of China, and supported by the SKLRD, Guangdong Provincial Key Laboratory of Vascular Diseases, Shanghai Nutrition and Health Research Institute of Chinese Academy of Sciences and Animal Platform.

The link of the original text of the paper:

https://www.ahajournals.org/doi/abs/10.1161/HYPERTENSIONAHA.121.17809