Background Platelets play a role in promoting inflammatory responses under several disease conditions. Platelets are activated in hypertensive patients. However, the mechanisms responsible for platelet‐mediating vascular inflammation are unknown. The present study investigated the role of platelets in promoting vascular inflammation following angiotensin II (Ang II ) stimulation, and the efficacy of antiplatelet intervention. Methods and Results Within a mouse model of Ang II infusion (490 ng/kg per min), we measured the portion of P‐selectin–positive platelets and platelet‐monocyte (P‐M) binding in blood samples, and platelet accumulation and P‐M binding in vessels under Ang II stimulation at days 1, 3, and 7. We tested the efficacy of clopidogrel (15 mg/kg per day, followed by 5 mg/kg per day) on Ang II ‐induced platelet activation, P‐M binding, vascular platelet accumulation, as well as vascular inflammation and remodeling at day 7 or 14. Clopidogrel reduced platelet vascular deposition (28.7±2.4% versus 18.3±2.9%), suppressed inflammatory cell infiltration (3.6±0.8×10 4 /vessel versus 2.3±1.2×10 4 /vessel) and oxidative stress, and attenuated vascular remodeling and dysfunction (55.0±5.5% versus 84.0±6.0%) following Ang II stimulation at day 7 or 14. Clopidogrel suppressed Ang II ‐induced P‐M binding both at circulating (13.4±3.3% versus 5.9±2.7%) and regional (33.4±4.3% versus 11.9±2.7%) levels. Conclusions Platelets play a critical role in vascular inflammation under Ang II stimulation, with a marked promotion of P‐M binding as an important mechanism. Clopidogrel prevented vascular inflammation in Ang II ‐infused mice.

The aim of the present study was to explore the effects of pannexin1 (Px1) protein channels on osteogenic differentiation of mesenchymal stem cells (MSCs) under mechanical stress stimulation. MSCs were isolated from Sprague Dawley rats (3 weeks old, weighing 100–120 g) and cultured in vitro. A safe concentration of carbenoxolone was determined (CBX, an inhibitor of Px1 channels; 100 µM) on MSCs using the Cell Counting Kit-8 (CCK8) method. MSCs were divided into 6 groups: Control, stress (4,000 µ strain), and stress following 3, 6, 12, and 24 h pretreatment with CBX. Stress groups were stimulated with mechanical stress for 15 min. Alkaline phosphatase (ALP) activity, type I collagen expression, intracellular calcium ion (Ca2+) concentration, Px1 expression, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated phosphorylation were determined. ALP activity was increased in the stress group, and this was prevented by pretreatment with CBX. Similarly, stress-induced increases in type I collagen expression, Ca2+ concentration, Px1 expression, and p38 MAPK phosphorylation decreased in the presence of CBX. ERK phosphorylation was decreased by stress, however was not affected by CBX treatment. Altogether, the results suggest that mechanical stress promoted the osteogenic differentiation of MSCs, and this promotion was inhibited by pretreatment with CBX, possibly through regulating the phosphorylation of p38 MAPK.

Diabetic retinopathy (DR) is a common complication of diabetes mellitus and has been considered a microvascular disease for a long time. However, recent evidence suggests that diabetic retinal neurodegeneration (DRN), which manifests as neuronal apoptosis, a decrease in optic nerve axons, and reactive gliosis, occurs prior to retinal microvascular alterations. Thioredoxin-interacting protein (TXNIP) is an endogenous inhibitor of thioredoxin (Trx), and it acts by inhibiting its reducing capacity, thereby promoting cellular oxidative stress. In addition, it participates in regulating multiple signaling pathways as a member of the α-arrestin family of proteins. Accumulating evidence suggests that TXNIP is upregulated in diabetes and plays a pivotal role in the pathophysiological process of DR. In this review, we summarized the role of TXNIP in DRN, aiming to provide evidence for DR treatment in the future.