Photoelasticity-based Evaluation Of Cellular Contractile Force For Phenotypic Discrimination Of Vascular Smooth Muscle Cells Scientific Reports

Non-coding RNAs, important epigenetic regulators, primarily include microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Targeting key molecules within the NF-κB pathway—such as circACTA2 and HMGB1/2—may help preserve the contractile phenotype of VSMCs and offers promising therapeutic strategies for vascular remodeling–related diseases. A variety of stimuli can activate this pathway in VSMCs, promoting their transition to a synthetic phenotype and accelerating pathological remodeling. Elucidating its molecular mechanisms not only enhances our understanding of vascular remodeling but also provides a promising foundation for the development of targeted therapeutic strategies aimed at preventing vascular graft failure and related pathologies. It involves the integration of multiple signaling pathways (MAPK, mTOR, NF-κB, TGF-β) and a complex network of non-coding RNAs (miRNAs, lncRNAs, circRNAs), which collectively orchestrate the transition from a contractile to a synthetic phenotype. The mechanism is initiated by endothelial dysfunction and amplified by the key driver PDGF-BB. A thorough understanding of PDGF-BB–mediated signaling pathways may provide essential theoretical support for the development of targeted therapies to prevent VGF.

Furthermore, the contribution of endogenous progenitor cells in the tunica media or adventitia remains to be further verified. In addition, VSMCs are thought to achieve phenotype switching through selective expression of marker genes. In ApoE−/− mice, NFATc1 deletion reduced CD137L-induced neointima formation . Chappell et al. showed that VSMCs-derived cells in the neointima of AS were usually formed by clonal expansion of a few VSMCs in tunica media . Another study showed that VSMC-derived foam cells carried a higher cholesterol burden than leukocyte derived foam cells . A recent study showed that in advanced coronary atherosclerotic plaque, 50% of foam cells express the VSMCs marker ACTA2. A recent lineage tracing experiment exploring the origin of foam cells in AS showed that manifold VSMCs, which should be quiescent in the tunica media, migrated to tunica intima and transform to macrophage-like VSMCs . Since vascular calcification occurs only in arteries but not in veins, it suggests that VSMCs, the specific component of arteries, play an irreplaceable role in arterial calcification.

These findings are important for a better understanding of the complex pathogenesis of atherosclerosis, which in turn can potentially inspire novel therapeutic strategies. In addition to the 2 types of VSMCs mentioned above, recent studies have uncovered a number of other phenotypes of VSMCs, which appear to exert diverse roles in atherosclerosis. Due to the strong plasticity of VSMC, it is feasible to treat vascular diseases by reversing VSMCs phenotype to contractile. For these life-threatening vascular diseases, existing treatments cannot reverse their aggravation. Importantly, the studies of VSMCs phenotypes provide new ideas and targets for pharmacological treatment.

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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 ooosch casino bonus 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.

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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.

A more complete understanding of the role of VSMC phenotype transition and the relative contributions of the different VSMC phenotypes can potentially aid the identification of new therapeutic targets and the development of new drugs that can modulate VSMC phenotypes and inhibit atherosclerosis progression. Studies to date have provided substantial insights into VSMC plasticity and phenotypic switching, and its roles in atherosclerosis. The single‐cell RNA sequencing technique provides transcriptomic data of individual cells and therefore can be applied to identify VSMCs of different types according to their gene expression profiles. In response to the nonspecific expression of Cre recombinase, He et al reported a dual recombinase‐mediated genetic lineage tracing technique.92 The combination of the Dre‐rox recombination system permits rigorous control of potential unintentional Cre‐loxP recombination, effectively improving the accuracy of the traditional Cre‐loxP approach in lineage tracing. The Myh11 transgene is located on the Y chromosome and so this line is unsuitable for studying female mice.

For the very first time, agent of the Special Operations Executive (SOE), Harry Hawker steps out of the shadows as the lead protagonist While Sniper Elite 5 included updates set in Vichy France, the team decided to make a standalone game set in this location because the team "felt that there was much more to explore". The game retained the same gameplay systems, though the team added some new features, such as a new grenade type and a new timed-based mode. Once in Amiens, Hawker finds out that when he finishes his mission by trapping the Zugwerfers for an RAF bombing, he will not be able to escape in time. The dam from the first mission is being repaired, however, one of the crashed RAF bombers had a bouncing bomb, which the Germans are studying.

Cholesterol‐induced phenotypic modulation of smooth muscle cells to macrophage/fibroblast‐like cells is driven by an unfolded protein response. Transdifferentiation of mouse aortic smooth muscle cells to a macrophage‐like state after cholesterol loading. Low LAL (lysosomal acid lipase) expression by smooth muscle cells relative to macrophages as a mechanism for arterial foam cell formation. Contribution of intimal smooth muscle cells to cholesterol accumulation and macrophage‐like cells in human atherosclerosis. BMAL1 modulates smooth muscle cells phenotypic switch towards fibroblast‐like cells and stabilizes atherosclerotic plaques by upregulating YAP1.

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, the vast majority of VSMCs are located in tunica media and represent quiescent contractile phenotype.

Hu CT, Shao YD, Liu YZ, Xiao X, Cheng ZB, Qu SL, Huang L, Zhang C. Oxidative stress in vascular calcification. Epigenetic control of smooth muscle cell differentiation and phenotypic switching in vascular development and disease. Atheroprotective roles of smooth muscle cell phenotypic modulation and the TCF21 disease gene as revealed by single‐cell analysis. Plaque evaluation by ultrasound and transcriptomics reveals BCLAF1 as a regulator of smooth muscle cell lipid transdifferentiation in atherosclerosis. Dichotomous roles of smooth muscle cell‐derived MCP1 (monocyte chemoattractant protein 1) in development of atherosclerosis. Ten‐eleven translocation‐2 (TET2) is a master regulator of smooth muscle cell plasticity.

Yap C, Mieremet A, de Vries CJM, Micha D, de Waard V. Six shades of vascular smooth muscle cells illuminated by KLF4 (Kruppel‐like factor 4). In addition, this article summarizes several methodologies that have been developed and used to study VSMC phenotypic switching and discusses their respective advantages and limitations. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. Upregulation of key enzymes like GLUT1, HK2, and PFKFB3 provides abundant ATP and metabolic intermediates, supporting migration, proliferation, and ECM synthesis in synthetic VSMCs. These findings suggest that targeting the miR-145/miR-143 axis may provide a potential strategy to prevent Hcy-induced VSMC phenotypic remodeling. In addition, Hcy activated the PI3K/AKT/mTOR signaling pathway by inhibiting miR-145 expression, inducing VSMC proliferation, migration, and transformation to a synthetic phenotype. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

Adipocyte‐derived factors regulate vascular smooth muscle cells through mineralocorticoid and glucocorticoid receptors. Zhang F, Guo X, Xia Y, Mao L. An update on the phenotypic switching of vascular smooth muscle cells in the pathogenesis of atherosclerosis. Yoshida T, Yamashita M, Hayashi M. Kruppel‐like factor 4 contributes to high phosphate‐induced phenotypic switching of vascular smooth muscle cells into osteogenic cells. Nakahara T, Kawai‐Kowase K, Matsui H, Sunaga H, Utsugi T, Iso T, Arai M, Tomono S, Kurabayashi M. Fibroblast growth factor 23 inhibits osteoblastic gene expression and induces osteoprotegerin in vascular smooth muscle cells. Toll‐like receptor 4 mediated oxidized low‐density lipoprotein‐induced foam cell formation in vascular smooth muscle cells via Src and Sirt1/3 pathway. Burger F, Baptista D, Roth A, da Silva RF, Montecucco F, Mach F, Brandt KJ, Miteva K. NLRP3 inflammasome activation controls vascular smooth muscle cells phenotypic switch in atherosclerosis. Zhang Z, Huang J, Wang Y, Shen W. Transcriptome analysis revealed a two‐step transformation of vascular smooth muscle cells to macrophage‐like cells.