RESUMEN
Endothelial dysfunction, and the differentiation of smooth muscle cells (SMCs) into proliferative, secretory phenotypes, are two major pathophysiological processes in atherosclerosis. SMCs have the potential to recruit macrophages in atherosclerotic plaques, in which macrophages drive inflammatory responses. In this study, we found that microRNA-503-5p (miR-503-5p) was enriched in either extracellular vesicles (EVs), secreted by oxidized low-density lipoprotein-treated macrophages, or the EVs from peripheral blood mononuclear cells of atherosclerosis patients. miR-503-5p was transferred intercellularly from macrophages to the co-cultured human coronary artery endothelial cells (HCAECs) and HCASMCs via EVs, thus reducing the proliferative and angiogenic abilities of HCAECs and accelerating the proliferative and migrating abilities of HCASMCs. Smad family members 1, 2 and 7 were negatively regulated by miR-503-5p in HCAECs and HCASMCs. miR-503-5p was verified as an enhancer of inflammatory cytokines and adhesion molecules released by macrophages, in part via the down-regulation of smad family members 1, 2 and 7. The inhibition of miR-503-5p by lentivirus reduced atherosclerotic lesion formations in the aorta of atherosclerotic mice. Our work demonstrated a miR-503-5p- and EV-mediated mechanism for macrophage communication with HCAECs and HCASMCs in atherosclerosis. miR-503-5p is pro-atherosclerotic stimuli that may be a therapeutic target for atherosclerosis treatment.
Asunto(s)
Aterosclerosis/inmunología , Comunicación Celular/genética , Vesículas Extracelulares/metabolismo , Macrófagos/inmunología , MicroARNs/metabolismo , Adulto , Animales , Aterosclerosis/sangre , Aterosclerosis/genética , Aterosclerosis/patología , Comunicación Celular/inmunología , Movimiento Celular/genética , Movimiento Celular/inmunología , Proliferación Celular/genética , Técnicas de Cocultivo , Vasos Coronarios/citología , Vasos Coronarios/patología , Modelos Animales de Enfermedad , Células Endoteliales/citología , Células Endoteliales/inmunología , Células Endoteliales/metabolismo , Endotelio Vascular/citología , Endotelio Vascular/patología , Femenino , Humanos , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/metabolismo , Lipoproteínas LDL/inmunología , Macrófagos/citología , Macrófagos/metabolismo , Masculino , Ratones , Ratones Noqueados para ApoE , Persona de Mediana Edad , Miocitos del Músculo Liso , Cultivo Primario de Células , Células RAW 264.7 , Células THP-1RESUMEN
BACKGROUND AND PURPOSE: Although many functional magnetic resonance imaging (fMRI) studies have investigated the language architecture and neurobiological mechanism underlying poststroke aphasia (PSA), the pathophysiological mechanisms of PSA still remain poorly understood. In addition to a limited number of subjects (<20) tested with different methodologies and stimuli, inconsistent reports of the brain regions involved have been a major factor. Thus, we conducted a meta-analysis of 12 peer-reviewed studies of abnormal brain activation regions in PSA patients at rest using activation likelihood estimation (ALE). RESULTS: A meta-analysis was performed based on 24 experiments with 497 total participants in 12 studies to establish the ALE of regional activation in PSA. Through experiments with PSA patients and healthy controls, we found that hypoactivation in PSA converged on the left superior frontal gyrus and the left parietal postcentral gyrus, whereas there was hyperactivation in the right cerebellar anterior lobe, left fusiform gyrus, left superior parietal lobule, and right subgyral hippocampus. CONCLUSION: Our study verified that dominant and nondominant language networks play roles in the recovery of language function.
