Muscle Cells Research Articles

Endothelial cell Piezo1 promotes vascular smooth muscle cell differentiation on large arteries.

Endothelial cell Piezo1 promotes vascular smooth muscle cell differentiation on large arteries.

Antisense oligonucleotide-mediated exon 27 skipping restores dysferlin function in dysferlinopathy patient-derived muscle cells.

Antisense oligonucleotide-mediated exon 27 skipping restores dysferlin function in dysferlinopathy patient-derived muscle cells.

Genomic and transcriptomic analyses reveal the genetic basis of leg diseases in laying hens.

Genomic and transcriptomic analyses reveal the genetic basis of leg diseases in laying hens.

Quantification of Cardiac Iron Overload at 3 T MRI in a Rabbit Model Utilizing ME-GRE T2* Sequence.

Myocardial iron overload can lead to myocardial dysfunction, muscle cell injury, and end-stage heart failure. The enhanced signal-to-noise ratio and technical advancements have made 3 T magnetic resonance imaging (MRI) more accessible in clinical settings. However, 3 T assessments for early diagnosis of myocardial iron overload are scarce. To evaluate the feasibility of myocardial iron quantification using 3 T MRI in a rabbit model of iron overload. Animal model. Overall, 40 male New Zealand white rabbits were categorized into control (N = 8; no treatment) and experimental (N = 32; weekly 200 mg/kg iron dextran injections) groups. 3 T MRI with multi-echo gradient echo (ME-GRE) T2* sequence. Each week, two experimental rabbits were randomly selected for blood collection to determine serum iron (SI) levels; their tissue was harvested to assess myocardial and hepatic iron deposition. Spearman's rank correlation tests were used to evaluate the correlations among R2*, cardiac iron concentration (CIC), liver iron concentration (LIC), total amount of iron injected, and SI levels. P ≤ 0.05 was considered statistically significant. The myocardial T2* value in the experimental group was significantly lower than that of the control group. An excellent correlation was observed between R2* values and CIC (r = 0.854). CIC moderately correlated with LIC (r = 0.712) and the total amount of iron injected (r = 0.698). A strong correlation was observed between the total amount of iron injected and LIC (r = 0.866). SI levels poorly correlated with the total amount of iron injected (r = 0.205, P = 0.277) and LIC (r = 0.170, P = 0.370) but fairly correlated with CIC (r = 0.415, P = 0.022). A 3 T MRI with an ME-GRE sequence may serve as a noninvasive method for evaluating cardiac iron content. N/A TECHNICAL EFFICACY: Stage 1.

ECM Modifications Driven by Age and Metabolic Stress Directly Promote Vascular Smooth Muscle Cell Osteogenic Processes.

The ECM (extracellular matrix) provides the microenvironmental niche sensed by resident vascular smooth muscle cells (VSMCs). Aging and disease are associated with dramatic changes in ECM composition and properties; however, their impact on VSMC phenotype remains poorly studied. Here, we describe a novel in vitro model system that utilizes endogenous ECM to study how modifications associated with age and metabolic disease impact VSMC phenotype. ECM was synthesized using primary human VSMCs and modified during culture or after decellularization. Integrity, stiffness, and composition of the ECM was measured using superresolution microscopy, atomic force microscopy, and proteomics, respectively. VSMCs reseeded onto the modified ECM were analyzed for viability and osteogenic differentiation. ECMs produced in response to mineral stress showed extracellular vesicle-mediated hydroxyapatite deposition and sequential changes in collagen composition and ECM properties. VSMCs seeded onto the calcified ECM exhibited increased extracellular vesicle release and Runx2 (Runt-related transcription factor 2)-mediated osteogenic gene expression due to the uptake of hydroxyapatite, which led to increased reactive oxygen species and the induction of DNA damage signaling. VSMCs seeded onto the nonmineralized, senescent ECM also exhibited increased Runx2-mediated osteogenic gene expression and accelerated calcification. In contrast, glycated ECM specifically induced increased ALP (alkaline phosphatase) activity, and this was dependent on RAGE (receptor for advanced glycation end products) signaling with both ALP and RAGE receptor inhibition attenuating calcification. ECM modifications associated with aging and metabolic disease can directly induce osteogenic differentiation of VSMCs via distinct mechanisms and without the need for additional stimuli. This highlights the importance of the ECM microenvironment as a key driver of phenotypic modulation acting to accelerate age-associated vascular pathologies and provides a novel model system to study the mechanisms of calcification.

Death-associated protein kinase 1 prevents hypoxia-induced metabolic shift and pulmonary arterial smooth muscle cell proliferation in PAH

Death-associated protein kinase 1 prevents hypoxia-induced metabolic shift and pulmonary arterial smooth muscle cell proliferation in PAH

Monotropein resists atherosclerosis by reducing inflammation, oxidative stress, and abnormal proliferation and migration of vascular smooth muscle cells.

Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR-/- mice given high-fat diet to investigate the effects of monotropein on atherosclerosis. Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.

The protective effect and potential mechanism of Zanthoxylum bungeanum Maxim. on atherosclerosis.

The protective effect and potential mechanism of Zanthoxylum bungeanum Maxim. on atherosclerosis.

MicroRNAs in vascular smooth muscle cells: Mechanisms, therapeutic potential, and advances in delivery systems.

MicroRNAs in vascular smooth muscle cells: Mechanisms, therapeutic potential, and advances in delivery systems.

Unraveling the molecular complexity of bicuspid aortopathy: Lessons from comparative proteomics.

Unraveling the molecular complexity of bicuspid aortopathy: Lessons from comparative proteomics.

SERCA2 dysfunction accelerates angiotensin II-induced aortic aneurysm and atherosclerosis by induction of oxidative stress in aortic smooth muscle cells.

SERCA2 dysfunction accelerates angiotensin II-induced aortic aneurysm and atherosclerosis by induction of oxidative stress in aortic smooth muscle cells.

Serum Uric Acid/Serum Creatinine Ratio and Chronic Vascular Lesions on Renal Biopsy: A Retrospective Observational Study.

Increased serum uric acid (SUA) levels are found in cardiovascular and kidney diseases, associated with the development of vascular injury. Uric acid stimulates the inflammatory pathways, promotes vascular smooth muscle cells proliferation, activates renin-angiotensin system leading to the development and progression of vascular damage. Renal function-normalized uric acid [SUA to serum creatinine ratio (SUA/SCr)] has been suggested to be a better indicator of uric acid. To investigate the correlation between SUA level and SUA/SCr in the development of chronic and vascular lesions (CVL) in patients with primary glomerulonephritis (GN). A retrospective observational study was conducted in 95 consecutive renal native biopsies performed at Policlinico Umberto I of Rome (Italy). Patient inclusion criteria were age ≥ 18 years, a renal biopsy confirming diagnosis of primary GN, the availability of complete demographic, clinical, pathological, and laboratory data. Median SCr was 1.06 mg/dl (IQR 0.77;1.70) with a median eGFR of 70.40 ml/min (IQR 40.40;105). Median SUA was 5.90 mg/dl (IQR 4.30;6.90) and median SUA/SCr was 4.70 (IQR 3.20;6.80). CVL were reported in 56 (58.9%) patients. Median SUA/SCr was significantly lower in patients with CVL than patients without CVL [3.95 (IQR 2.65;6) vs 5.90 (IQR 4.30;7.20), p<0.01]. Logistic regression analysis showed that SUA/SCr ≤ 4.05 [OR 5.451 (95% CI 1.222;24.325), p<0.05] was independently associated with CVL. CVL play a crucial role in the progression of kidney disease. SUA/SCr ≤ 4.05 is associated with CVL in patients with primitive GN.

Study on the mechanism of Huangqi Chifeng decoction regulating ferroptosis inhibiting smooth muscle cells derived foam cell formation.

Study on the mechanism of Huangqi Chifeng decoction regulating ferroptosis inhibiting smooth muscle cells derived foam cell formation.

Heparin suppresses FoxO1/pFoxO1 signaling axis in vascular smooth muscle cells.

Heparin suppresses FoxO1/pFoxO1 signaling axis in vascular smooth muscle cells.

YBX1 Modulates Intimal Hyperplasia by Regulating Expression and Alternative Splicing of Cell Cycle Associated Genes in RASMCs.

YBX1, a DNA-/RNA-binding protein, is implicated in various diseases, yet its role in intimal hyperplasia (IH) remains unclear. This study investigates YBX1's function in rat aortic smooth muscle cells (RASMCs) through knockdown experiments. Results show that YBX1 knockdown reduces cell proliferation and migration while inducing apoptosis. ELISA and western blot analyses revealed increased levels of the anti-inflammatory factor IL10 and markers for phenotypic transformation, Calponin and Myocardin. Transcriptome sequencing identified 1598 differentially expressed genes (DEGs), with 347 upregulated and 1251 downregulated. Upregulated DEGs were linked to pathways like ECM-receptor interaction and Wnt signalling, while downregulated genes involved cell cycle and p53 signalling. Additionally, 629 significant alternative splicing events were noted, primarily affecting pathways related to cell division and migration. Integrated analysis of YBX1-bound RNAs and RNA-seq data highlighted key DEGs, such as CCNB1 and TPM1, which are crucial for vascular cell behaviour. This study underscores YBX1's vital role in RASMCs and suggests potential therapeutic targets for IH treatment.

Challenges and opportunities in targeting epigenetic mechanisms for pulmonary arterial hypertension treatment.

Challenges and opportunities in targeting epigenetic mechanisms for pulmonary arterial hypertension treatment.

Effects of alpha-ketoisocaproate in oxidative stress-induced C2C12 myotubes via inhibition of p38 MAPK and ERK1/2.

Effects of alpha-ketoisocaproate in oxidative stress-induced C2C12 myotubes via inhibition of p38 MAPK and ERK1/2.

A Preliminary Study of Effect of Melatonin on Inflammation and Hypoxia-Related Factors in a Mouse Model of Elastase-Induced Intracranial Aneurysm.

Intracranial aneurysms (IAs) are relatively common cerebrovascular anomalies. Melatonin could modulate inflammatory and offers neuroprotective effects, and its role in IA has not been fully elucidated. An elastase-induced IA mouse model was constructed and melatonin (150mg/kg) was administered to investigate its therapeutic effects on IA. Aneurysm formation was observed by bromophenol blue gelatin perfusion, and the pathology changes in IA mice were examined using hematoxylin-eosin (HE) staining. The potential mechanisms of melatonin treatment of IA were explored using western blot, enzyme-linked immunosorbent, real-time qPCR, immunohistochemistry, and flow cytometry. An H2O2-reduced human brain vascular smooth muscle cells (HBVSMC) injury model was also constructed. The formation of aneurysms was observed in the circle of Willis in the IA mice. Melatonin treatment alleviated the thinning of blood vessel walls and disruption of the internal elastic lamina in IA mice. The levels of Bcl-2 were significantly increased and Bax and cleaved caspase-3 were decreased in IA mice with melatonin treatment, suggesting reduced apoptosis. Furthermore, melatonin reduced levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) in IA mice. The H2O2-reduced HBVSMCs model showed consistent results. Melatonin reduced levels of krüppel-like factor 6 (KLF6) in IA mice. Importantly, melatonin significantly reduced levels of regulatory T cells (Treg), hypoxia-inducible factor (HIF)-1α, nuclear factor interleukin 3-regulated (NFIL3), TCDD-inducible poly-ADP-ribose polymerase (TIPARP), and increased levels of monocytes in IA mice. Melatonin mitigates IA injury by modulating immune cells and hypoxia-related factors. These findings provide an exploratory foundation for therapeutic strategies in IA.

Enhanced vascular contraction induced by exposure to angiotensin II mediated by endothelin-1 biosynthesis following PKCβ activation.

Protein kinase C (PKC) reportedly plays a role in the pathogenesis of many vascular dysfunction-related conditions. In this study, we investigated whether PKCβ is associated with vascular contractile changes induced by angiotensin II (Ang II) exposure. Long-term (24 h) treatment of rat aortae and mesenteric arteries in Ang II-containing culture medium enhanced 5-hydroxytryptamine (5-HT)-induced vascular contraction in a dose-dependent manner, in association with enhanced phosphorylation of PKCβ S660. Increased contraction induced by Ang II treatment was also observed in endothelium-denuded aorta. Enhanced contraction induced by Ang II was markedly diminished by the knockout of the PKCβ gene or treatment with LY333531 and CGP53353 (PKCβ inhibitors). Cycloheximide (protein synthesis inhibitor) blocked the Ang II-induced enhanced contraction. Gene expression profiling and real-time PCR analyses showed marked upregulation of endothelin-1 (ET-1) expression in Ang II-treated aorta but was not observed in PKCβ-knockout aorta. Ang II increased the secretion of ET-1 peptide in endothelium-intact and -denuded aortae. Ang II-induced enhancement of vascular contraction was diminished by BQ-123 (ETAR blocker). In vivo treatment with Ang II (250 ng/kg/min) for 7 days increased phosphorylation of PKCβ S660 in rat vascular tissue and increased the in vitro contractile responses to 5-HT and in vivo systolic blood pressure, but these changes were largely absent in PKCβ-knockout experiments. These data suggest that long-term exposure to Ang II increases vascular smooth muscle contraction and blood pressure elevation, mediated by activation of PKCβ and subsequent biosynthesis of ET-1 in vascular smooth muscle cells.NEW & NOTEWORTHY We studied the role of PKCβ in Ang II-induced hypertension using a rat model. Our study showed that PKCβ plays a key role in Ang II-induced vascular hypercontractility. Our results also suggest that transcriptional activation-mediated ET-1 expression in vascular smooth muscle is responsible for this vascular change as a downstream pathway of PKCβ activation, which leads to blood pressure elevation. This Ang II-PKCβ-ET-1 mechanism may affect vascular homeostasis in hypertension.

New insights into the relationship of mitochondrial metabolism and atherosclerosis.

New insights into the relationship of mitochondrial metabolism and atherosclerosis.