Myostatin mediates abdominal aortic atherosclerosis progression by inducing vascular smooth muscle cell dysfunction and monocyte recruitment.

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.

Systemic vascular inflammation in abdominal aortic aneurysm patients: a contrast-enhanced PET/CT study.

AIM: The aim of this paper was to investigate the presence of systemic vascular inflammation and its relationship with risk factors and biomarkers of systemic inflammation related to atherosclerosis in asymptomatic abdominal aortic aneurysm (AAA) patients. METHODS: Thirty AAA patients and 30 age-matched controls underwent contrast-enhanced 2-deoxy-2-[18F]fluoro-D-glucose (FDG) PET/CT. C-reactive protein, erythrocyte sedimentation rate, white blood cell count and differential, serum fibrinogen, D-dimer and full lipid panel were also evaluated. Region of interest analyses were performed to obtain target-to-background (TBR) metabolism of aorta, subclavian, carotid, iliac arteries and AAA. CT-based arterial calcium load (CL) was evaluated. Arterial Metabolism and CL intergroup differences were tested (unpaired t-test). Linear regression analysis was performed only between blood biomarkers on one side and both TBR and ACL of the arterial districts that resulted significantly different between patients and controls on the other. In all the analyses P values <0.05 were considered significant. RESULT: FDG-uptake was higher with respect to controls in aorta, carotid and iliac arteries (P<0.01, P<0.007, P<0.04 respectively). AAA and aorta metabolism showed an inverse correlation with HDL-chol (P<0.02 and P<0.01, respectively) while only aorta showed a direct correlation with lymphocytes' count (P<0.02). Carotid metabolism was directly correlated with monocytes' count and C-reactive protein concentration (P<0.02 and P<0.004, respectively). CONCLUSION: The present findings support the relevance of systemic vascular inflammation in all phases of atherosclerosis-related disorders. Moreover they confirm the concept that acute ischemic syndromes might represent the local result of a systemic inflammation rather than the focal involvement of a single arterial lesion.