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Background: Atherosclerosis is a main cause of multiple cardiovascular diseases, and cell damage of human umbilical vein endothelial cells (HUVECs) was reported to participate in the development of atherosclerosis. In this study, we aimed to study the action of Astragaloside IV (ASV) on AS development using in vitro AS cell model. Methods: MTT assay, EdU staining assay, and flow cytometry were utilized for detection of cell proliferation and apoptosis, respectively. The protein expression of histone deacetylase 9 (HDAC9), Bax, Bcl‐2, p‐P65, P65, p‐IκBα, and IκBα was gaged using western blot. The angiogenesis was evaluated by tube formation assay. The inflammatory response was evaluated by ELISA kits. SOD activity and MDA level were detected using the matched commercial kits. RT‐qPCR was used for HDAC9 mRNA expression measurement. Results: Oxidized low‐density lipoprotein (ox‐LDL) significantly repressed cell proliferation, angiogenesis, and enhanced apoptosis, inflammation, and oxidative stress in HUVECs. ASV addition could alleviate ox‐LDL‐caused cell damage in HUVECs. Moreover, HDAC9 was overexpressed in AS patients and AS cell model. Functionally, HDAC9 knockdown also exhibited the protective role in ox‐LDL‐treated HUVECs. In addition, ASV treatment protected against ox‐LDL‐induced damage in HUVECs via targeting HDAC9. ASV could inactivate the NF‐κB pathway via regulating HDAC9 in AS cell model. Conclusion: ASV exerted the protective effects on ox‐LDL‐induced damage in HUVECs through the HDAC9/NF‐κB axis. [ABSTRACT FROM AUTHOR]

Background Recent evidence suggested that ClC-3, encoding Cl − channel or Cl − /H + antiporter, plays a critical role in regulation of a variety of physiological functions. However, remarkably little is known about whether ClC-3 is involved in atherosclerosis. This study aims to establish the involvement and direct role of ClC-3 in atherogenesis and underlying mechanisms by using ClC-3 and ApoE double null mice. Methods and results After a 16-week western-type high-fat diet, the ClC-3 +/+ ApoE −/− mice developed widespread atherosclerotic lesions in aorta. However, the lesion size was significantly reduced in aorta of ClC-3 −/− ApoE −/− mice. Compared with the ClC-3 +/+ controls, there was significantly decreased ox-LDL binding and uptake in isolated peritoneal macrophages from ClC-3 −/− mice. Moreover, the expression of scavenger receptor SR-A, but not CD36, was significantly decreased in both ClC-3 −/− peritoneal macrophages and aortic lesions from ClC-3 −/− ApoE −/− mice. These findings were further confirmed in ox-LDL-treated RAW264.7 macrophages, which showed that silence of ClC-3 inhibited SR-A expression, ox-LDL accumulation and foam cell formation, whereas overexpression of ClC-3 produced the opposite effects. In addition, ClC-3 siRNA significantly inhibited, whereas ClC-3 overexpression increased, the phosphorylation of JNK/p38 MAPK in ox-LDL-treated RAW264.7 foam cells. Pretreatment with JNK or p38 inhibitor abolished ClC-3-induced increase in SR-A expression and ox-LDL uptake. Finally, the increased JNK/p38 phosphorylation and SR-A expression induced by ClC-3 could be mimicked by reduction of [Cl − ] i by low Cl − solution. Conclusions Our findings demonstrated that ClC-3 deficiency inhibits atherosclerotic lesion development, possibly via suppression of JNK/p38 MAPK dependent SR-A expression and foam cell formation. [ABSTRACT FROM AUTHOR]