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Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Macrophage-Derived Exosomal MALAT1 Induced by Hyperglycemia Regulates Vascular Calcification Through miR-143-3p/MGP
Kou-Gi Shyu1, Bao-Wei Wang2, Wei-Jen Fang2
1Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, 95 Wen-Chang Road, Taipei 111, Taiwan.
Abstract:
Metastasis-associated lung adenocarcinoma transcript 1(MALAT1) is associated with vascular calcification and diabetes-related complications. However, the effect of exosomal MALAT1 derived from macrophages induced by hyperglycemia on vascular calcification (VC) remains unclear. In this study, we investigated the effect of VC and its regulatory mechanisms in cultured vascular smooth muscle cells (VSMCs) and diabetic rats by exosomal MALAT1 derived from macrophages treated with high levels of glucose. Macrophages and VSMCs were cultured in 25 mM glucose. Macrophages exposed to high glucose exhibited increased expression of exosomal MALAT1. When transferred to VSMCs, exosomal MALAT1 significantly suppressed the expression of miR-143-3p while upregulating Matrix Gla protein (MGP, an inhibitor of VC) mRNA and protein levels. Interventions using MALAT1 siRNA or miR-143-3p mimics effectively reversed this effect. Both MALAT1 siRNA and overexpression of miR-143-3p significantly increased the calcium content in cultured VSMCs and in the carotid artery of diabetic rats following balloon injury. Balloon injury to the carotid artery in diabetic rats treated with macrophage-derived exosomes significantly increased the expression of MALAT1 and MGP while reducing the expression of miR-143-3p in the carotid artery. These findings demonstrate that macrophage-derived exosomal MALAT1 modulates VC via the MALAT1/miR-143-3p/MGP axis under hyperglycemic conditions. The results suggest that targeting exosomal MALAT1 may offer a novel and effective therapeutic approach for mitigating VC in metabolic disorders such as diabetes.
Insights
High glucose induces macrophage exosomal MALAT1, promoting vascular calcification (VC) by suppressing miR-143-3p and upregulating MGP. Targeting exosomal MALAT1 may treat VC in diabetes.
Area of Science:
- Biomedical research
- Molecular biology
- Cardiovascular research
Background:
- Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is linked to vascular calcification (VC) and diabetes complications.
- The role of exosomal MALAT1 from hyperglycemia-induced macrophages in VC is not fully understood.
Purpose of the Study:
- To investigate the impact of exosomal MALAT1 from high-glucose-treated macrophages on vascular calcification.
- To elucidate the regulatory mechanisms involved in VC under hyperglycemic conditions.
Main Methods:
- Cultured human macrophages and vascular smooth muscle cells (VSMCs) in high glucose (25 mM).
- Analyzed exosomal MALAT1 expression and its transfer to VSMCs.
- Utilized MALAT1 siRNA and miR-143-3p mimics for intervention studies.
- Assessed VC in cultured VSMCs and in a diabetic rat carotid artery injury model.
Main Results:
- High glucose increased exosomal MALAT1 in macrophages.
- Exosomal MALAT1 suppressed miR-143-3p and upregulated Matrix Gla protein (MGP) in VSMCs.
- MALAT1 inhibition or miR-143-3p restoration reversed VC.
- Exosomal MALAT1 promoted VC in VSMCs and diabetic rat carotid arteries.
Conclusions:
- Macrophage-derived exosomal MALAT1 drives VC through the MALAT1/miR-143-3p/MGP pathway under hyperglycemia.
- Targeting exosomal MALAT1 presents a potential therapeutic strategy for VC in metabolic disorders like diabetes.
