Background and Aims. Vascular smooth muscle cells (VSMCs) are central components of atherosclerotic plaque. Loss of VSMCs through apoptotic cell death can cause fibrous cap thinning, necrotic core formation, and calcification that may destabilize plaque. Elevated glucocorticoid levels caused by psychological stress promote VSMC apoptosis and can exacerbate atherosclerosis in mice and humans. Changes in the levels of antiapoptosis microRNA-25 (miR-25) have been linked with heart disease, inflammation, VSMC phenotype, oxidative stress, and apoptosis. Here, we investigated the pathways and mechanisms of glucocorticoid-induced apoptosis of mouse VSMCs and the protective role of miR-25. Methods. Primary mouse VSMCs were cultured +/- corticosterone for 48 h. Apoptosis, ROS, apoptotic protein activities, miR-25, MOAP1, a miR-25 target, and p70S6 kinase were quantified at intervals. The roles of miR-25 were assessed by treating cells with lenti-pre-miR-25 and anti-miR-25. Results. VSMC apoptosis, caspase-3 activity, and Bax were increased by corticosterone, and cell death was paralleled by marked loss of miR-25. Protection was conferred by pre-miR-25 and exacerbated by anti-miR-25. Pre-miR-25 conferred reduced expression of the proapoptotic protein MOAP1, and the protective effects of pre-miR-25 were abrogated by overexpressing MOAP1. The antiapoptotic effects of miR-25 were paralleled by inhibition of the p70S6K pathway, a convergence target for the survival signaling pathways, and protection by pre-miR-25 was abrogated by the p70S6k inhibitor rapamycin. Conclusions. MicroRNA-25 blocks corticosterone-induced VSMC apoptosis by targeting MOAP1 and the p70S6k pathway. Therapeutic manipulation of miR-25 may reduce atherosclerosis and unstable plaque formation associated with chronic stress.
BackgroundNummular headache is a distinct headache disorder characterized by a rounded or elliptical symptomatic area that is typically 2 to 6 cm in diameter and does not change in shape or size with time. Although the pathomechanism is still not clear, nummular headache is thought to be a primary headache disorder. To date, more than 250 cases have been reported; the symptoms of this disease vary, but no cases with scalp temperature changes in the symptomatic areas have been reported yet. In this study, we present three patients with a new manifestation of nummular headache, in which the symptomatic areas of the scalp were colder or warmer than normal areas; we believe that our work might be helpful for medical practitioners and researchers.Case presentationThe temperature differences between the symptomatic areas and the normal areas were tested in three patients with nummular headache accompanied by changes in scalp temperature. Three patients’ symptomatic areas were either colder or warmer than the normal areas. In every case, we took measurements from the painful site and from the opposite side of the head. The margin of error was 0.01 °C, and the difference was statistically significant (P < 0.01).ConclusionWe firmly believe that our study will provide an enriched understanding of the variation in clinical manifestations of nummular headache. Our observations might also have clinical implications regarding the pathomechanism of this disease, which remains largely unclear at present.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.