High Glucose Levels Promote Switch to Synthetic Vascular Smooth Muscle Cells via Lactate/GPR81
Hyperglycemia, lipotoxicity, and insulin resistance are known to increase the secretion of extracellular matrix from cardiac fibroblasts as well as the activation of paracrine signaling from cardiomyocytes, immune cells, and vascular cells, which release fibroblast-activating mediators. However, the...
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MDPI AG
2024-01-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/13/3/236 |
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| author | Jing Yang Glenn R. Gourley Adam Gilbertsen Chi Chen Lei Wang Karen Smith Marion Namenwirth Libang Yang |
| author_facet | Jing Yang Glenn R. Gourley Adam Gilbertsen Chi Chen Lei Wang Karen Smith Marion Namenwirth Libang Yang |
| author_sort | Jing Yang |
| collection | DOAJ |
| description | Hyperglycemia, lipotoxicity, and insulin resistance are known to increase the secretion of extracellular matrix from cardiac fibroblasts as well as the activation of paracrine signaling from cardiomyocytes, immune cells, and vascular cells, which release fibroblast-activating mediators. However, their influences on vascular smooth muscle cells (vSMCs) have not been well examined. This study aimed to investigate whether contractile vascular vSMCs could develop a more synthetic phenotype in response to hyperglycemia. The results showed that contractile and synthetic vSMCs consumed high glucose in different ways. Lactate/GPR81 promotes the synthetic phenotype in vSMCs in response to high glucose levels. The stimulation of high glucose was associated with a significant increase in fibroblast-like features: synthetic vSMC marker expression, collagen 1 production, proliferation, and migration. GPR81 expression is higher in blood vessels in diabetic patients and in the high-glucose, high-lipid diet mouse. The results demonstrate that vSMCs assume a more synthetic phenotype when cultured in the presence of high glucose and, consequently, that the high glucose could trigger a vSMC-dependent cardiovascular disease mechanism in diabetes via lactate/GPR81. |
| first_indexed | 2024-03-08T03:59:43Z |
| format | Article |
| id | doaj.art-81b9250985654c228d6e1e6220fcafad |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-08T03:59:43Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-81b9250985654c228d6e1e6220fcafad2024-02-09T15:09:40ZengMDPI AGCells2073-44092024-01-0113323610.3390/cells13030236High Glucose Levels Promote Switch to Synthetic Vascular Smooth Muscle Cells via Lactate/GPR81Jing Yang0Glenn R. Gourley1Adam Gilbertsen2Chi Chen3Lei Wang4Karen Smith5Marion Namenwirth6Libang Yang7Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan 442000, ChinaDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USADepartment of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USADepartment of Food Science and Nutrition, CFANS, University of Minnesota, St Paul, MN 55108, USADepartment of Food Science and Nutrition, CFANS, University of Minnesota, St Paul, MN 55108, USADepartment of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USADepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USADepartment of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USAHyperglycemia, lipotoxicity, and insulin resistance are known to increase the secretion of extracellular matrix from cardiac fibroblasts as well as the activation of paracrine signaling from cardiomyocytes, immune cells, and vascular cells, which release fibroblast-activating mediators. However, their influences on vascular smooth muscle cells (vSMCs) have not been well examined. This study aimed to investigate whether contractile vascular vSMCs could develop a more synthetic phenotype in response to hyperglycemia. The results showed that contractile and synthetic vSMCs consumed high glucose in different ways. Lactate/GPR81 promotes the synthetic phenotype in vSMCs in response to high glucose levels. The stimulation of high glucose was associated with a significant increase in fibroblast-like features: synthetic vSMC marker expression, collagen 1 production, proliferation, and migration. GPR81 expression is higher in blood vessels in diabetic patients and in the high-glucose, high-lipid diet mouse. The results demonstrate that vSMCs assume a more synthetic phenotype when cultured in the presence of high glucose and, consequently, that the high glucose could trigger a vSMC-dependent cardiovascular disease mechanism in diabetes via lactate/GPR81.https://www.mdpi.com/2073-4409/13/3/236smooth muscle cellsphenotype changeglucoselactateGPR81diabetes |
| spellingShingle | Jing Yang Glenn R. Gourley Adam Gilbertsen Chi Chen Lei Wang Karen Smith Marion Namenwirth Libang Yang High Glucose Levels Promote Switch to Synthetic Vascular Smooth Muscle Cells via Lactate/GPR81 Cells smooth muscle cells phenotype change glucose lactate GPR81 diabetes |
| title | High Glucose Levels Promote Switch to Synthetic Vascular Smooth Muscle Cells via Lactate/GPR81 |
| title_full | High Glucose Levels Promote Switch to Synthetic Vascular Smooth Muscle Cells via Lactate/GPR81 |
| title_fullStr | High Glucose Levels Promote Switch to Synthetic Vascular Smooth Muscle Cells via Lactate/GPR81 |
| title_full_unstemmed | High Glucose Levels Promote Switch to Synthetic Vascular Smooth Muscle Cells via Lactate/GPR81 |
| title_short | High Glucose Levels Promote Switch to Synthetic Vascular Smooth Muscle Cells via Lactate/GPR81 |
| title_sort | high glucose levels promote switch to synthetic vascular smooth muscle cells via lactate gpr81 |
| topic | smooth muscle cells phenotype change glucose lactate GPR81 diabetes |
| url | https://www.mdpi.com/2073-4409/13/3/236 |
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