Obesity, a risk factor for atherosclerosis development and progression, is marked by excessive reactive oxygen species (ROS) production. We previously demonstrated that high-glucose (HG) conditions in Show more
Obesity, a risk factor for atherosclerosis development and progression, is marked by excessive reactive oxygen species (ROS) production. We previously demonstrated that high-glucose (HG) conditions induce mitochondrial ROS (mtROS) production in aortic endothelial cells (ECs). However, the link between elevated mtROS levels in obesity and atherosclerosis progression remains unclear. This study aimed to investigate whether endothelial-specific mtROS suppression by overexpressing manganese superoxide dismutase (MnSOD) could attenuate atherosclerosis progression in high-fat diet (HFD)-induced obese apolipoprotein E-deficient (ApoE KO) mice. Atherosclerotic lesion formation did not differ significantly between normal chow-fed control ApoE KO mice and endothelial cell-specific MnSOD-overexpressing ApoE KO (eMnSOD-Tg/ApoE KO) mice. However, in HFD-fed groups, eMnSOD-Tg/ApoE KO mice exhibited reduced atherosclerotic lesion size, decreased relative ROS levels, and lower Our findings demonstrate that endothelial-specific MnSOD overexpression suppresses obesity-related atherosclerosis in ApoE KO mice. mtROS plays a pivotal role in obesity-associated atherosclerosis, and targeting endothelial mtROS may offer a therapeutic strategy for preventing vascular complications in obesity. Show less
Atherosclerosis is a chronic inflammatory disease wherein macrophage polarization critically influences lesion development. Dipeptidyl peptidase-4 (DPP4), a serine protease expressed on immune cells, Show more
Atherosclerosis is a chronic inflammatory disease wherein macrophage polarization critically influences lesion development. Dipeptidyl peptidase-4 (DPP4), a serine protease expressed on immune cells, has been implicated in vascular inflammation; however, its cell type-specific roles remain unclear. This study aimed to determine whether Dpp4 deficiency, particularly in hematopoietic cells, affects macrophage polarization and atherosclerosis progression. Using Apoe-knockout (ApoeKO) and Apoe- and Dpp4-double knockout mice as well as bone marrow transplantation models, we evaluated the impact of systemic and myeloid-specific Dpp4 deficiency on macrophage phenotype and atherogenesis. In bone marrow-derived macrophages, Dpp4 deficiency enhanced M2 marker expression (Arg1, Ym1, Mgl2, and Fizz1) and increased the proportion of CD206 Show less
Liver X receptor (LXR) alpha/beta dual agonists are candidate medicaments for the treatment of metabolic syndrome, because their biological actions include increasing cholesterol efflux mediated by LX Show more
Liver X receptor (LXR) alpha/beta dual agonists are candidate medicaments for the treatment of metabolic syndrome, because their biological actions include increasing cholesterol efflux mediated by LXRbeta. However, their clinical application is currently limited by their enhancing effect on triglyceride (TG) synthesis mediated by LXRalpha. Combination of an LXRalpha-selective antagonist with an LXRalpha/beta dual agonist may overcome this disadvantage. In the present work, structural development studies of phenethylphenyl phthalimide 9, which possesses LXRalpha/beta dual-antagonistic activity and alpha-glucosidase-inhibitory activity, led to the LXRalpha-selective antagonist 23f. Specific alpha-glucosidase inhibitors were also obtained. Show less