Changes in retardation with time when the chemical reagent was applied to the cell to alter the cellular contraction state. Under the assumption that the refractive index stays constant, retardation measurements provide information on the mechanical state. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.
Additionally, high homoarginine reinforces VSMCs osteogenic transition and vascular calcification given the background of hyperphosphatemia . Whereas, a recent study found that adventitial VSCs did not differentiate into the pathogenic VSMCs in atherosclerosis . Earlier studies believed that tunica adventitia derived mesenchymal-like VSMCs contribute to atherosclerotic plaque growth and CKD-induced vascular calcification . Once vascular injury occurred, VSCs migrate to the tunica media and differentiate into mesenchymal-like VSMCs for repairing . In addition to deriving from contractile VSMCs, Mesenchymal-like VSMCs can also derive from SCA1+ vascular stem cells (VSCs) originally located in the tunica adventitia. The potential plasticity shown by VSMCs is comprehensive and inherent, since VSMCs necessitate high abilities of proliferation, migration, and ECM secretion (such as collagen and elastin) in response to vascular morphogenesis and frequent vascular injury. Whereas, contractile VSMCs spontaneously modify their phenotype instantaneously to a highly synthetic phenotype when the vessel is physically or chemically damaged. In healthy adults, oosch casino the vast majority of VSMCs are located in tunica media and represent quiescent contractile phenotype.
Buffer solutions—such as the University of Wisconsin solution, TiProtec, and He solution—can better maintain ion homeostasis and physiological pH. These solutions provide superior protection of endothelial structure and function compared to AWB and normal saline (93). The proposed protective mechanisms include the preservation of eNOS activity, which is abundantly expressed in the adventitia, and the retention of perivascular adipose tissue markers such as leptin and adiponectin (85, 86). These approaches provide a diversified portfolio for improving vein graft patency. Further elucidation of their roles may not only deepen our understanding of IH but also provide theoretical foundations and therapeutic targets for developing effective intervention strategies. To facilitate comparison and provide an integrated overview of the evidence discussed above, representative studies describing non-coding RNAs-mediated regulation of VSMCs phenotypic switching, including molecular targets and functional consequences, are summarized in Table 2. These molecules participate in the regulation of VSMCs phenotypic switching through intricate molecular mechanisms and play essential roles in the onset and progression of cardiovascular diseases (Figure 2).
Malonyl-CoA decarboxylase (MCD) is an endogenous inhibitor of CPT1 and a key regulatory enzyme of FAO . As a result, FAO is suppressed, causing accumulation of intracellular long-chain fatty acids and reduced palmitate oxidation activity, ultimately enhancing VSMC proliferation and migration . In Elovl6-/- mice, the formation of new intima is significantly reduced, the number of Ki-67-positive cells and the expression of α-SMA and SM22α are reduced. The latest study found that Elovl6 co-localizes with α-SMA -positive cells during vascular injury. The energy produced by aerobic glycolysis can be provided by FAO, and the activity of glycolysis is regulated by the feedback of FAO metabolites . In TRAP1-knockout rats, acetyl-CoA and citrate were increased, and the expression levels of senescence markers (P53, P21, and P16) and H4K12la in VSMCs were decreased, while lipid accumulation, plaque area, and necrotic core size in the aorta were reduced . In addition, SM22α can synergistically enhance G6PD activity, stimulate the PPP to increase NADPH production, maintain GSH homeostasis, and promote VSMC proliferation and migration . Immunoprecipitation revealed that the N-terminal domain of G6PD interacts with VDAC1 and competes with Bax for binding to VDAC1, alleviating VSMC apoptosis by reducing VDAC1 oligomerization and maintaining the synthetic phenotype of VSMC .
Rapamycin (mTOR inhibitor) failed to reverse these changes, indicating a potential role between impaired autophagy mediated by the KLF4-dependent mTOR signaling pathway and the VSMC phenotypic remodeling . Leucine supplementation activates the SIRT1-Foxo1 pathway through the Slc3a2/Slc7a5 transporter, inhibiting the transformation of VSMC to a synthetic phenotype, vascular inflammatory response, and ROS generation during aging . At the same time, single-cell RNA sequencing and microarray analysis found that glutamate metabolism-related enzymes Glutamate-Ammonia Ligase and Glutaminase (GLS) and glutamate receptor subunits GRIA1 and GRIA2 were highly expressed in VSMCs. The latest study found that glutamine and serine as anaplerosis of the TCA cycle increased in unstable plaques . Adipokine stimulation upregulates CD36, a key fatty acid transporter in VSMCs, resulting in enhanced fatty acid uptake and lipid deposition, ERK pathway activation, and subsequent VSMC proliferation and inflammatory responses .
This value is larger than the cell retardation measured in the current study, approximately 0.3 nm (Fig. 4h), implying that changes in cell retardation would not be detected in aortic tissue. According to our previous study31, the retardation of aortic tissue with a thickness of 100 µm is approximately 30 nm. This study demonstrates that retardation measurement is useful for evaluating the cell phenotype in VSMCs. Generally, SFs in cells dynamically change their position and structure on this time scale. Figure 2b of the present study shows that retardation increased mainly in the central region upon calyculin A application, implying that retardation is increased by SF contraction. (d–f) Changes in (d) cell retardation, RetCell; (e) cell area, ACell; and (f) total cell retardation, RetCellTotal, with time. (a–c) Typical time-lapse images of retardation of single cells after application of (a) DMEM (control), (b) calyculin A, and (c) Y solution.
Shi J, Yang Y, Cheng A, Xu G, He F. Metabolism of vascular smooth muscle cells in vascular diseases. Atherosclerotic plaques are characterized by the accumulation of cholesterol crystals in the arterial wall, a fibrous cap rich in extracellular matrix produced by vascular smooth muscle cells (VSMCs) and infiltration of immune cells (such as monocytes-macrophages, T cells, and mast cells) 3, 4. Photoelasticity-based evaluation of cellular contractile force for phenotypic discrimination of vascular smooth muscle cells. Photoelasticity-based evaluation of cellular contractile force for phenotypic discrimination of vascular smooth muscle cells Coronary artery bypass grafting, intimal hyperplasia, phenotypic switching, vascular smooth muscle cells, vein graft failure Zargham R, Touyz RM, Thibault G. Alpha 8 integrin overexpression in de‐differentiated vascular smooth muscle cells attenuates migratory activity and restores the characteristics of the differentiated phenotype. Generation and comparative analysis of an Itga8‐CreER (T2) mouse with preferential activity in vascular smooth muscle cells. Shioi A, Nishizawa Y, Jono S, Koyama H, Hosoi M, Morii H. Beta‐glycerophosphate accelerates calcification in cultured bovine vascular smooth muscle cells.
Zhang P, Guan Y, Chen J, Li X, McConnell BK, Zhou W, Boini KM, Zhang Y. Contribution of p62/SQSTM1 to PDGF‐BB‐induced myofibroblast‐like phenotypic transition in vascular smooth muscle cells lacking Smpd1 gene. Adipocytic differentiation and liver x receptor pathways regulate the accumulation of triacylglycerols in human vascular smooth muscle cells. Feil S, Fehrenbacher B, Lukowski R, Essmann F, Schulze‐Osthoff K, Schaller M, Feil R. Transdifferentiation of vascular smooth muscle cells to macrophage‐like cells during atherogenesis. Extensive proliferation of a subset of differentiated, yet plastic, medial vascular smooth muscle cells contributes to neointimal formation in mouse injury and atherosclerosis models. KLF4‐dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis. Regulation of differentiation of vascular smooth muscle cells.