Activated endothelial cells (ECs) play an important role in the development of atherosclerosis (AS) because they form neointima resulting from abnormal vascular smooth muscle cell (VSMC) hyperplasia. TET2 was recently reported as a major regulator of the phenotypic switch of VSMCs, and it also protects ECs from noxious stimuli and represses inflammation in AS. The purpose of the present study is to determine whether activation of CD137 signaling can regulate the function of VSMCs by altering endothelial TET2 expression and to explore the potential mechanisms. VSMCs were isolated from C57BL/6 J mice, and the influence of ECs on VSMCs was analyzed using a co-culture system. Western blotting was used to detect the protein expression levels of TET2 and CD9, CD81, and CD63 as well as VSMC phenotypic markers. RT-PCR was performed to detect the TET2 mRNA levels. EdU proliferation assay and transwell migration assay were employed to assess the functions of VSMCs. EXO-spin kits were used to extract and purify exosomes. Transmission electron microscopy and nanoparticle tracking analysis were applied to characterize exosomes. ECs transduced with the TET2-overexpression lentivirus showed that the activation of endothelial CD137 signaling decreased TET2 expression and the TET2 content in exosomes. EC-derived exosomes were internalized by VSMCs, which inhibited phenotypic switching in vitro and neointimal formation in vivo. However, exosomes derived from CD137-activated ECs exhibited weakened protective effects on VSMCs. In conclusion, activation of endothelial CD137 signaling attenuated the repressive effects of EC-derived exosomes on platelet-derived growth factor (PDGF)-BB-induced phenotypic switching of VSMCs and neointimal formation after carotid injury.

Ferroptosis is a form of iron-dependent cell death caused by an excessive accumulation of reactive oxygen species and lipid peroxidation. The importance of ferroptosis in the occurrence and progression of various diseases is gradually being recognized; however, the exact biological effects and potential mechanisms of endothelial cell ferroptosis remain unclear. The endothelium forms the innermost layer of the blood vessels and lymphatic vessels. It acts as an important functional interface, responds to various pathological stimuli and causes endothelial dysfunction. Here, we review recent findings to elucidate the role of ferroptosis in endothelial cells under different pathophysiologic settings.

Nuclear factor of activated T cells (NFAT) was first identified as a transcription factor about 3 decades ago and was not well studied until the development of immunosuppressant. Numerous studies confirm that calcineurin/NFAT signaling is very important in the development of vasculature and cardiovascular system during embryogenesis and is involved in the development of vascular diseases such as hypertension, atherosclerosis and restenosis. Recent studies demonstrated that NFAT proteins also regulate immune response and vascular cells in the pulmonary microenvironment. In this review, we will discuss how different NFAT isoforms contribute to pulmonary vascular remodeling and potential new therapeutic targets for treating pulmonary arterial hypertension.

Atherosclerosis is a chronic inflammatory disease. Research has focused on identifying specific serum biomarkers to detect vulnerable plaques. These markers serve as diagnostic tools for acute coronary syndrome and assist in identifying high-risk patients. However, the existing data are limited and conflicting. This study tested the hypothesis that CD137 levels identify patients with acute coronary syndrome who are at a heightened risk for recurrent cardiac events. The levels of soluble CD137 (sCD137) were measured using ELISA in 180 patients with acute coronary syndrome and 120 patients with acute chest pain. Platelet activation was assessed by flow cytometry. Receiver operating characteristic curve analysis was performed to evaluate the prognostic characteristics of sCD137. The levels of sCD137 were elevated in 75 patients with acute coronary syndromes and 20 patients with acute chest pain (>35.0 ng/ml). In patients with acute coronary syndrome, elevated sCD137 levels (>35.0 ng/ml) indicated an increased risk for major adverse cardiovascular events (OR =1.93, 95% CI: 1.39-2.54). Elevated serum levels of sCD137 and cTnT were correlated with a significantly increased risk of major adverse cardiovascular events in both groups after 30 days, six months and nine months of follow-up. The increased sCD137 levels were significantly correlated with the levels of troponin I (r = 0.4799, p<0.001). Importantly, 26 patients with normal cTnI levels had acute coronary syndrome. However, elevated sCD137 levels identified these patients as a being high-risk subgroup (OR = 2.14, 95% CI: 1.25-4.13). Elevated sCD137 levels indicate an increased risk of cardiovascular events in patients with acute coronary syndrome. Soluble CD137 may be a useful prognostic marker or indicator for adverse events in patients with acute coronary syndrome.