MRTFA overexpression promotes conversion of human coronary artery smooth muscle cells into lipid-laden foam cells
| Autor: | Sébastien Daudi, Johan Holmberg, Mari Ekman, Gabriella Kalliokoski, Azra Alajbegovic, Sebastian Albinsson, Catarina Rippe, Sigurdur Ragnarsson, Karl Swärd, Fatima Daoud |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Vascular smooth muscle Physiology Myocytes Smooth Muscle Vascular Remodeling 030204 cardiovascular system & hematology Muscle Smooth Vascular 03 medical and health sciences 0302 clinical medicine Neointima Transcriptional regulation medicine Humans Foam cell Pharmacology Chemistry Pinocytosis Transdifferentiation Lipid Metabolism Coronary Vessels Up-Regulation Cell biology HEK293 Cells 030104 developmental biology medicine.anatomical_structure Receptors LDL Myocardin Cell Transdifferentiation LDL receptor Trans-Activators Molecular Medicine lipids (amino acids peptides and proteins) Foam Cells Artery |
| Zdroj: | Vascular Pharmacology. 138:106837 |
| ISSN: | 1537-1891 |
| Popis: | Objective Smooth muscle cells contribute significantly to lipid-laden foam cells in atherosclerotic plaques. However, the underlying mechanisms transforming smooth muscle cells into foam cells are poorly understood. The purpose of this study was to gain insight into the molecular mechanisms regulating smooth muscle foam cell formation. Approach and results Using human coronary artery smooth muscle cells we found that the transcriptional co-activator MRTFA promotes lipid accumulation via several mechanisms, including direct transcriptional control of LDL receptor, enhanced fluid-phase pinocytosis and reduced lipid efflux. Inhibition of MRTF activity with CCG1423 and CCG203971 significantly reduced lipid accumulation. Furthermore, we demonstrate enhanced MRTFA expression in vascular remodeling of human vessels. Conclusions This study demonstrates a novel role for MRTFA as an important regulator of lipid homeostasis in vascular smooth muscle cells. Thus, MRTFA could potentially be a new therapeutic target for inhibition of vascular lipid accumulation. |
| Databáze: | OpenAIRE |
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