The Effect of mascRNA on the Phenotype Transition and Mitophagy in Vascular Smooth Muscle Cells Exposed to Hypoxia.
A primary complication of atherosclerosis(AS) is characterized by chronic inflammatory and mitochondrial dysfunction, both of which play critical roles in the disease's progression. This study aims to investigate the regulatory role of mascRNA in mediating the hypoxia-induced phenotypic transition of vascular smooth muscle cells (VSMCs).
An AS model was established, and the aortic plaque area was assessed by Oil Red O staining. Human VSMCs were divided into five groups: normoxia, hypoxiainduced, negative control (pGV-NC), mascRNA overexpression (pGV-mascRNA), and inhibitor-treated. Quantitative PCR (qPCR) was utilized to detect the expression of mascRNA, vWF, and MMP2. Western blotting was performed to detect the expression of phenotypic transformation-related proteins.
In high-fat diet (HFD)-fed mice, the expression of mascRNA was significantly decreased in the aortas (P < 0.05). Hypoxia led to a reduction in mascRNA levels, an upregulation of synthetic markers, and increased reactive oxygen species (ROS) in VSMCs. Overexpression of mascRNA suppressed VSMC migration and proliferation, enhanced mitophagy, and inhibited the PI3K-AKT pathway. Our study has been the first to demonstrate mascRNA play a crucial role in VSMC phenotypic transformation and functions via regulation of mitophagy. These findings highlight mascRNA's role in AS development and provide a theoretical basis for its clinical applications, but in vivo experiments are called for to validate its anti-AS effect.
MascRNA suppressed hypoxia-induced phenotypic transformation of VSMCs, potentially through the modulation of the PI3K-AKT signaling pathway and the enhancement of mitochondrial autophagy. These findings indicate a prospective therapeutic application of mascRNA in AS.
An AS model was established, and the aortic plaque area was assessed by Oil Red O staining. Human VSMCs were divided into five groups: normoxia, hypoxiainduced, negative control (pGV-NC), mascRNA overexpression (pGV-mascRNA), and inhibitor-treated. Quantitative PCR (qPCR) was utilized to detect the expression of mascRNA, vWF, and MMP2. Western blotting was performed to detect the expression of phenotypic transformation-related proteins.
In high-fat diet (HFD)-fed mice, the expression of mascRNA was significantly decreased in the aortas (P < 0.05). Hypoxia led to a reduction in mascRNA levels, an upregulation of synthetic markers, and increased reactive oxygen species (ROS) in VSMCs. Overexpression of mascRNA suppressed VSMC migration and proliferation, enhanced mitophagy, and inhibited the PI3K-AKT pathway. Our study has been the first to demonstrate mascRNA play a crucial role in VSMC phenotypic transformation and functions via regulation of mitophagy. These findings highlight mascRNA's role in AS development and provide a theoretical basis for its clinical applications, but in vivo experiments are called for to validate its anti-AS effect.
MascRNA suppressed hypoxia-induced phenotypic transformation of VSMCs, potentially through the modulation of the PI3K-AKT signaling pathway and the enhancement of mitochondrial autophagy. These findings indicate a prospective therapeutic application of mascRNA in AS.