Myostatin mediates abdominal aortic atherosclerosis progression by inducing vascular smooth muscle cell dysfunction and monocyte recruitment
| Autor: | Manrico Balbi, Maria Bertolotto, Giorgio Ghigliotti, Samantha Milanesi, Giacomo Garibotto, Claudio Brunelli, Daniela Verzola, Fabrizio Montecucco, Silvano Garibaldi, Chiara Barisione, Domenico Palombo, Barbara Villaggio, Jh Lindeman, Pietro Ameri |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Neointima CCR2 medicine.medical_specialty Vascular smooth muscle THP-1 Cells Muscle Proteins Myostatin 030204 cardiovascular system & hematology Monocytes Muscle Smooth Vascular Article 03 medical and health sciences 0302 clinical medicine Cell Movement Internal medicine Medicine Macrophage Animals Humans Aorta Abdominal Cells Cultured Cell Proliferation Multidisciplinary biology business.industry Monocyte Skeletal muscle Anatomy Atherosclerosis Actins Rats Cytoskeletal Proteins 030104 developmental biology Endocrinology medicine.anatomical_structure biology.protein cardiovascular system Disease Progression Smoothelin business |
| Zdroj: | Scientific Reports Scientific Reports, 7 |
| Popis: | Myostatin (Mstn) is a skeletal muscle growth inhibitor involved in metabolic disorders and heart fibrosis. In this study we sought to verify whether Mstn is also operative in atherosclerosis of abdominal aorta. In human specimens, Mstn expression was almost absent in normal vessels, became detectable in the media of non-progressive lesions and increased with the severity of the damage. In progressive atherosclerotic lesions, Mstn was present in the media, neointima, plaque shoulder and in infiltrating macrophages. Mstn co-localized with α-smooth muscle actin (α-SMA) staining and with some CD45+ cells, indicating Mstn expression in VSMCs and bloodstream-derived leukocytes. In vitro, Mstn was tested in VSMCs and monocytes. In A7r5 VSMCs, Mstn downregulated proliferation and Smoothelin mRNA, induced cytoskeletal rearrangement, increased migratory rate and MCP-1/CCR2 expression. In monocytes (THP-1 cells and human monocytes), Mstn acted as a chemoattractant and increased the MCP-1-dependent chemotaxis, F-actin, α-SMA, MCP-1 and CCR2 expression; in turn, MCP-1 increased Mstn mRNA. Mstn induced JNK phosphorylation both in VSMCs and monocytes. Our results indicate that Mstn is overexpressed in abdominal aortic wall deterioration, affects VSMCs and monocyte biology and sustains a chronic inflammatory milieu. These findings propose to consider Mstn as a new playmaker in atherosclerosis progression. |
| Databáze: | OpenAIRE |
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