Phenotypic plasticity of vascular smooth muscle cells in vascular calcification: Role of mitochondria

Abstract

Vascular calcification (VC) is an important hallmark of cardiovascular disease, the osteo-/chondrocyte phenotype differentiation of vascular smooth muscle cells (VSMCs) is the main cause of vascular calcification. Accumulating evidence shows that mitochondrial dysfunction may ultimately be more detrimental in the VSMCs calcification. Mitochondrial participate in essential cellular functions, including energy production, metabolism, redox homeostasis regulation, intracellular calcium homeostasis, apoptosis, and signal transduction. Mitochondrial dysfunction under pathological conditions results in mitochondrial reactive oxygen species (ROS) generation and metabolic disorders, which further lead to abnormal phenotypic differentiation of VSMCs. In this review, we summarize existing studies targeting mitochondria as a treatment for VC, and focus on VSMCs, highlighting recent progress in determining the roles of mitochondrial processes in regulating the phenotype transition of VSMCs, including mitochondrial biogenesis, mitochondrial dynamics, mitophagy, mitochondrial energy metabolism, and mitochondria/ER interactions. Along these lines, the impact of mitochondrial homeostasis on VC is discussed.

Mitochondria-Targeted Natural Antioxidant Nanosystem for Diabetic Vascular Calcification Therapy

“…Hyperglycemia induces mitochondrial electron transport chain dysfunction and reduces mitochondrial membrane potential, resulting in mitochondrial dysfunction and cellular homeostasis disruption. Consequently, an upsurge in ROS production triggers pathways that promote the transition of VSMCs to an osteogenic phenotype, thereby aggravating VC. − To effectively inhibit VC, it is essential to reduce oxidative stress and repair mitochondrial damage. Mitochondria targeting was first studied using the BODIPY@ PEG–PLGA and BODIPY@TPP/PEG–PLGA nanoparticles.…”

“…The use of T4O@TPP/PEG–PLGA brought about a substantial rise in the ratio, demonstrating mitochondrial repair. Perturbation of mitochondrial dynamics is crucial for maintaining mitochondrial homeostasis due to an imbalance in mitochondrial fission and fusion processes. ,− In order to evaluate the impact of T4O@TPP/PEG–PLGA on mitochondrial dynamics, the protein expression levels of dynamin-related protein 1 (DRP1) and mitofusin 1 (MFN1) were assessed, which plays crucial roles in mitochondrial fission and fusion processes . In Figure E,F, HG treatment increased DRP1 expression and decreased MFN1 expression.…”

A Modified Protocol for the Isolation, Culture, and Characterization of Human Smooth Muscle Cells from the Umbilical Cord

“…In atherosclerosis, VSMC phenotypic switching has a role in the initiation, stability, and, subsequently, the transfer of plaques [ 12 , 13 ]. Myointimal thickening and arterial occlusion arise from damage to the endothelium and exposure of VSMCs to circulating blood components such as oxidized lipoproteins [ 14 ]. In addition, conditions such as hyperglycemia and hyperlipidemia have been shown to transform the contractile phenotype of VSMCs into a synthetic phenotype, which plays a key role in the development of vascular diseases [ 4 ].…”

Biological function, mediate cell death pathway and their potential regulated mechanisms for post-mortem muscle tenderization of PARP1: A review

“…When energy is exhausted, apoptosis is inhibited, energy dependent life processes in myocytes stop, cell membranes are disrupted, and cytoplasm leaks out, leading to cell necrosis. Mitochondria are central regulators of apoptosis and provide sites for metabolic pathways such as oxidative phosphorylation, tricarboxylic acid cycle, energy conversion, and calcium ion storage under normal conditions ( 89 , 90 ). After animal slaughter, the disruption of communication between muscle tissue and the outside world leads to tissue ischemia and hypoxia, which then leads to excessive ROS production in the metabolic processes of muscle cells.…”