RNA m6A methylation and regulatory proteins in pulmonary arterial hypertension.

m6A (N6­methyladenosine) is the most common and abundant apparent modification in mRNA of eukaryotes. The modification of m6A is regulated dynamically and reversibly by methyltransferase (writer), demethylase (eraser), and binding protein (reader). It plays a significant role in various processes of mRNA metabolism, including regulation of transcription, maturation, translation, degradation, and stability. Pulmonary arterial hypertension (PAH) is a malignant cardiopulmonary vascular disease characterized by abnormal proliferation of pulmonary artery smooth muscle cells. Despite the existence of several effective and targeted therapies, there is currently no cure for PAH and the prognosis remains poor. Recent studies have highlighted the crucial role of m6A modification in cardiovascular diseases. Investigating the role of RNA m6A methylation in PAH could provide valuable insights for drug development. This review aims to explore the mechanism and function of m6A in the pathogenesis of PAH and discuss the potential targeting of RNA m6A methylation modification as a treatment for PAH.

Role of macrophages in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary vascular disease characterized by progressive pulmonary artery pressure elevation, increased pulmonary vascular resistance and ultimately right heart failure. Studies have demonstrated the involvement of multiple immune cells in the development of PAH in patients with PAH and in experimental PAH. Among them, macrophages, as the predominant inflammatory cells infiltrating around PAH lesions, play a crucial role in exacerbating pulmonary vascular remodeling in PAH. Macrophages are generally polarized into (classic) M1 and (alternative) M2 phenotypes, they accelerate the process of PAH by secreting various chemokines and growth factors (CX3CR1, PDGF). In this review we summarize the mechanisms of immune cell action in PAH, as well as the key factors that regulate the polarization of macrophages in different directions and their functional changes after polarization. We also summarize the effects of different microenvironments on macrophages in PAH. The insight into the interactions between macrophages and other cells, chemokines and growth factors may provide important clues for the development of new, safe and effective immune-targeted therapies for PAH.