Current Evidence on the Potential Role of Endothelial SHP-1 in Pulmonary Vascular Remodeling Associated With Pulmonary Hypertension

Pulmonary hypertension (PH) is characterized by an abnormally high pressure within the pulmonary arteries, which can be attributed to various factors. Severe diseases affecting pulmonary vessels may result in heart failure and potentially lead to death; these conditions are linked to significant mortality and unfavorable outcomes. Approximately 1% of adults worldwide have PH, and this condition may affect up to 10% of people older than 65 years. Currently, the mechanisms involved in the development of PH are not fully known and are thought to result from multiple coordinated factors. This lack of understanding remains a bottleneck in clinical practice. Numerous studies have confirmed that pulmonary artery endothelial cell (PAEC) dysfunction plays an important role in occlusive pulmonary vascular remodeling and the pathogenesis of PH. Src homology region 2 domain-containing phosphatase-1 (<i>SHP-1</i>) is a regulatory molecule that negatively modulates various cellular mediators and growth factors, primarily playing a negative regulatory role in signal transduction pathways. This review mainly presents an in-depth exploration of the key signaling pathways through which <i>SHP-1</i> regulates the expression of endothelial cells (ECs), thereby influencing various physiological functions, including proliferation, migration, oxidative stress, angiogenesis, apoptosis, autophagy, the inflammatory response, and vascular permeability. Furthermore, the potential mechanisms through which endothelial <i>SHP-1</i> plays a role in pulmonary vascular remodeling in PH are discussed. These findings underscore <i>SHP-1</i> as an encouraging therapeutic target for preventing and managing PH.