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.

Characteristics of exercise intolerance in different subgroups of pulmonary arterial hypertension associated with congenital heart disease.

BACKGROUND: Exercise intolerance is a major manifestation of pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). We aimed to investigate the characteristics of exercise intolerance in different subgroups of PAH-CHD. METHODS: We retrospectively enrolled 171 adult patients with PAH-CHD and 30 age and sex-matched healthy subjects and performed cardiopulmonary exercise testing. Gas exchange parameters, including peak oxygen uptake (peak V̇o2), anaerobic threshold, and the slope of ventilatory equivalent for carbon dioxide (V̇e/V̇co2 slope), were recorded. RESULTS: The median age of patients at enrollment was 27.8 years, and 131 (76.6%) were female. Peak V̇o2 was reduced in patients compared to healthy controls (median, 14.8 ml/kg/min versus 26.9 ml/kg/min, p < 0.001). Of all 171 patients, 60 (35.1%) had Eisenmenger syndrome, 35 (20.5%) had PAH associated with systemic-to-pulmonary shunts (PAH-SP), 39 (22.8%) had PAH with small defects (PAH-SD), and 37 (21.6%) had PAH after cardiac defect correction (PAH-CD). Patients with Eisenmenger syndrome had the lowest peak V̇o2 (p = 0.003) and the highest V̇e/V̇co2 slope (p = 0.012), compared with other patients, representing the worst exercise capacity and ventilatory efficiency. Patients with PAH-SP had the best exercise capacity among the four groups, indicated by the highest peak V̇o2 (p = 0.003) compared with other patients. Peak V̇o2 was negatively correlated with pulmonary vascular resistance (r = -0.411, p < 0.001). CONCLUSIONS: Exercise capacity was severely reduced in patients with PAH-CHD. Among the four subgroups, patients with Eisenmenger syndrome had the worst exercise capacity and ventilatory efficiency.

Tracking the Stepwise Formation of a Water-Soluble Fluorescent Tb12 Cluster for Efficient Doxorubicin Detection.

Doxorubicin (DOX) is an anthraquinone drug used for the efficient treatment of a variety of tumors in human beings. Unfortunately, its poor biodegradability causes incomplete metabolism in the body. Therefore, it is of great significance to synthesize a sensitive and selective material for DOX detection. In this paper, we report a water-soluble Tb12 cluster and track its step-by-step formation (L → Tb1L1 → Tb2L1 → Tb2L2 → Tb3L2 → Tb4L2 → Tb12L6). Tb12 can be used to determine the presence of DOX, which quenches the luminescence of the Tb12 aqueous solution, and the detection limit can reach 13 nM (KSV = 8.7 × 105 M-1). Tb12 has advantages of high sensitivity and high selectivity for the detection of DOX in a simulated environment of human urine and serum.