Suppression of EC‐SOD by oxLDL During Vascular Smooth Muscle Cell Proliferation

Abstract

Reactive oxygen species (ROS) produced by endothelial cells and macrophages play important roles in atherogenesis because they promote the formation of oxidized low-density lipoproteins (oxLDL). Extracellular-superoxide dismutase (EC-SOD) is mainly produced by vascular smooth muscle cells (VSMCs), is secreted into the extracellular space, and protects cells from the damaging effects of the superoxide anion. Thus, the expression of EC-SOD in VSMCs is crucial for protecting cells against atherogenesis; however, oxLDL-induced changes in the expression of EC-SOD in VSMCs have not yet been examined. We herein showed that oxLDL decreased EC-SOD mRNA and protein levels by binding to lectin-like oxidized LDL receptor-1 (LOX-1). Moreover, we demonstrated the significant role of mitogen-activated protein kinase (MEK)/extracellular-regulated protein kinase (ERK) signaling in oxLDL-elicited reductions in the expression of EC-SOD and proliferation of VSMCs. The results obtained with the FCS treatment indicate that oxLDL-elicited reductions in the expression of EC-SOD are related to the proliferation of VSMCs. We herein showed for the first time that luteolin, a natural product, restored oxLDL-induced decreases in the expression of EC-SOD and proliferation of VSMCs. Collectively, the results of the present study suggest that oxLDL accelerates the development of atherosclerosis by suppressing the expression of EC-SOD and also that luteolin has potential as a treatment for atherosclerosis. J. Cell. Biochem. 117: 2496-2505, 2016. © 2016 Wiley Periodicals, Inc.

Persistent myopathy despite release of partial obstruction: in vivo reversal of dysfunction and transcriptional responses using rapamycin

“…However, QPCR for these genes using a larger dataset showed that these three target genes increase during obstruction, persist in REL and are profoundly inhibited by rapamycin. All three encode extracellular proteins, and have known effects on mesenchymal and smooth muscle differentiation . Indeed, we saw that they have diverging effects on SMC number and SMC phenotype (Figure E).…”

“…All three encode extracellular proteins, and have known effects on mesenchymal and smooth muscle differentiation. [73][74][75][76][77][78] Indeed, we saw that they have diverging effects on SMC number and SMC phenotype ( Figure 6E).…”

SIRT1 inhibition causes oxidative stress and inflammation in patients with coronary artery disease

“…In addition, a study has shown that LOX-1 expression levels are activated in several pathological scenarios or systemic diseases, such as hypertension, diabetes, and hypercholesterolemia [24]. Activated LOX-1 facilitates the production of free radicals and impairs antioxidant level, thereby causing oxidative stress in the circulatory system [35]. SIRT1 negatively regulates LOX-1 expression by modulating the LOX-1 promoter [36].…”

CAPE increases the expression of SOD3 through epigenetics in human retinal endothelial cells

“…(34,35) It has been reported that CAPE is decomposed into caffeic acid and phenethyl alcohol by intracellular esterase, and caffeic acid with catechol skeleton possess anti-oxidative properties. (8,36) We recently reported that a treatment with CAPE suppressed monocyte adhesion to endothelial cells by inhibiting the accumulation of intracellular ROS.…”