Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Myocytes, Smooth Muscle”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2026

LncRNA H19 promotes vascular remodeling by inhibiting MFN2.

Neointimal hyperplasia, featuring excessive proliferation and migration of vascular smooth muscle cells (VSMCs), is crucial in vascular remodeling diseases. Long non-coding RNA (lncRNA) H19 promotes vascular remodeling, yet underlying mechanisms remain incompletely elucidated. Here, we investigated whether H19 acts via its derivative miR-675-5p. Bioinformatics found a conserved H19/miR-675-5p/MFN2 (mitofusin 2) axis. Cell assays were performed to evaluate the effects of H19 and miR-675-5p on VSMC proliferation and migration. The dual-luciferase reporter gene assay was used to assess the interaction between miR-675-5p and Mfn2 mRNA. The mouse model of common carotid artery ligation was used to evaluate the role of H19 in neointimal hyperplasia. Our data suggested that knockdown of H19 inhibited VSMC proliferation and migration, as well as neointimal hyperplasia. Mechanistically, H19 regulated MFN2 through miR-675-5p, leading to ERK1/2 (extracellular signal-regulated kinase 1/2) activation. In conclusion, we suggest that targeting the H19/miR-675-5p/MFN2/ERK1/2 axis may help to treat vascular remodeling diseases.

Animals↗
PubMed2025

The impact of m6A methyltransferase METTL3 on airway remodeling in bronchial asthma.

BACKGROUND: Methyltransferase-like 3 (METTL3) is known to play a role in asthma airway remodeling and cell proliferation. Adenylate kinase 4 (AK4) regulates the proliferation of pulmonary artery smooth muscle cells and exerts its effects through the protein kinase B (AKT) pathway. However, the role of METTL3 and AK4-AKT in bronchial smooth muscle cells remains unclear. METHODS: Systemic METTL3 knockout mice and a mouse model of asthma were established. Airway remodeling was assessed using pulmonary function tests, histopathological staining, and Western blot analysis. RNA sequencing (RNA-seq) was performed to detect changes in gene expression following METTL3 knockdown. The 5-ethynyl-2'-deoxyuridine (EdU) assay was used to evaluate cell proliferation. Finally, the expression levels of relevant proteins were validated by Western blotting. RESULTS: Compared with the control model group, the METTL3 knockout group showed significantly reduced inflammatory cell infiltration, decreased collagen fiber deposition, and attenuated airway smooth muscle hyperplasia. RNA-seq revealed that the expression of numerous proliferation-related genes, including AK4, was upregulated following METTL3 knockdown. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these genes were primarily enriched in the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. The EdU assay demonstrated that METTL3 knockdown inhibited cell proliferation. Western blot validation showed increased AK4 expression in lung tissues of the METTL3 knockout group compared to the control group, while phosphorylated AKT (p-AKT) levels were reduced. CONCLUSIONS: METTL3 knockout inhibits airway smooth muscle hyperplasia and alleviates airway remodeling in asthma. This effect may be mediated through the regulation of AK4 and the AKT signaling pathway.

Airway Remodeling↗
PubMed2025

Comprehensive evaluation of differential expression of piRNAs in abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a prevalent and fatal cardiovascular condition characterized by a high incidence rate and nonspecific clinical manifestations, with no effective preventive or therapeutic measures currently available. Piwi-interacting RNAs (piRNAs) have been identified as significant biomarkers for disease diagnosis due to their essential functions in transposon suppression, maintenance of genomic stability, immune response, and epigenetic modulation. The piRNA is intimately associated with various diseases such as cardiac hypertrophy, tumors, and neurodegeneration, yet its role in AAA is unclear. In this study, we employed gene sequencing to analyze the piRNA expression profiles in AAA vascular tissues and predicted variations in their target genes. Our findings revealed a total of 1368 piRNAs with abnormal expression in the AAA group relative to the control group, including 1240 up-regulated and 128 down-regulated piRNAs (|log2(fold change)|&#xa0;&#x2265;&#xa0;1.0), with 82 demonstrating significant differences (P&#xa0;<&#xa0;0.05). Through bioinformatics analysis, it was determined that the Wnt signaling pathway, calcium signaling, TNF-&#x3b1; and the p53 pathway are crucial mechanisms by which piRNAs contribute to the development of AAA. RT-qPCR confirmed that hsa_piR_011324 was the most significantly up-regulated piRNA in AAA (P&#xa0;<&#xa0;0.0001), corroborating RNA sequencing results. Further results indicate that hsa_piR_011324 promotes phenotypic transformation of human aortic vascular smooth muscle cells (HAVSMCs), enhances the activity of matrix metalloproteinases (MMPs), increased up-regulation of inflammation-related markers IL-1&#x3b2; and TNF-&#x3b1;, and induces apoptotic processes. In conclusion, the present study emphasizes the important regulatory role of hsa_piR_011324 in AAA, suggesting that it holds promise as a prospective target for diagnostic and therapeutic intervention.

Aortic Aneurysm, Abdominal↗
PubMed2026

Generation of Fibrin-Based Three-Dimensional Engineered Vascular Tissues from Human Aortic Smooth Muscle Cells for Proteomic Analysis.

Vascular smooth muscle cells (SMCs) reside within the medial layer of blood vessels, where they interact with an extracellular matrix (ECM) composed of collagen, elastin, and proteoglycans to maintain vascular structure and function. Aberrant ECM remodeling contributes to multiple vascular diseases; however, conventional two-dimensional culture systems do not adequately recapitulate the three-dimensional (3D) cellular and matrix environment required to study SMC-ECM interactions and matrix remodeling. This protocol describes the generation of engineered vascular tissues (EVTs) from primary human aortic SMCs cultured within fibrin-based 3D hydrogels. Following casting between flexible polydimethylsiloxane posts, EVTs undergo cellular alignment, contraction, and deposit de novo ECM, providing a physiologically relevant platform for studying vascular matrix biology. The protocol details tissue fabrication, culture, harvesting, and downstream analysis of newly deposited ECM by immunofluorescence staining. In addition, a workflow is presented for qualitative and quantitative characterization of EVT-derived proteins using Western blotting and mass spectrometry-based proteomics. Sequential protein extraction enables assessment of soluble and ECM-enriched protein fractions, facilitating in-depth evaluation of ECM composition. This platform provides a reproducible approach for investigating ECM production and remodeling by human SMCs in a 3D environment.

Humans↗
PubMed2026

The association of cardiovascular health with new-onset pulmonary hypertension and the mediating role of proteomic signatures.

BACKGROUND: The cardiovascular health (CVH) metrics have been reported to play an important role in the development of noncommunicable chronic diseases, yet its link to pulmonary hypertension (PH) risk and the underlying biological mechanisms remain unclear. This study aimed to investigate the association of CVH with PH risk and elucidate the mediating role of plasma proteomic signatures. METHODS: A total of 279 220 participants without PH at enrollment of the UK Biobank were included. Cox regression was used to quantify the association between CVH and incident PH. Proteome-wide association analysis, mediation analysis, and functional enrichment analysis were conducted to identify protein mediators. Key hub proteins were further validated at the transcriptional level through quantitative polymerase chain reaction (qPCR) in an animal model of PH, as well as at the protein level, and by macrophage-specific knockdown of interleukin (IL)-6 and CCL4 to evaluate its impact on rat pulmonary artery smooth muscle cell (PASMC) migration and proliferation. RESULTS: Over a median 13.2-year follow-up, 1325 PH cases occurred. Compared to the lowest CVH, participants with moderate and high CVH had 59% [hazard ratio (HR): 0.41; 95% confidence interval (CI): 0.33-0.49] and 82% (HR: 0.18; 95% CI: 0.14-0.23) lower risk, respectively. Proteomic analyses revealed that this association was significantly mediated by a distinct plasma protein signature. Pathway enrichment analysis indicates that proteins are significantly enriched in inflammatory/immune pathways, and key hub proteins were identified as participating in the central mechanism pathway. In the lung tissue of PH rat models, the mRNA and protein expression levels of IL-6 and C-C motif chemokine ligand 4 (CCL4) were significantly elevated. Furthermore, functional assays demonstrated that knockdown of IL-6 or CCL4 in macrophages significantly attenuated the migration and proliferation of rat PASMCs in vitro. CONCLUSION: High CVH level, defined by Life's Essential 8 (LE8), is significantly linked to a reduced risk of developing PH. This protective effect is primarily mediated by a proteomic signature, revealing the role of signaling pathways such as cytokine-cytokine receptor interaction in the prevention of PH.

Hypertension, Pulmonary↗
PubMed2026

Generation and validation of a Myh11Dre-Spp1Cre intersectional mouse model for lineage tracing of disease-associated smooth muscle cell states.

BACKGROUND: Phenotypic modulation of vascular smooth muscle cells (VSMCs) is a hallmark of vascular remodeling and cardiovascular disease. Recent lineage-tracing and single-cell transcriptomic studies have identified secreted phosphoprotein 1 (SPP1) as a prominent marker associated with disease-associated VSMC states, particularly those linked to fibrotic remodeling and vascular calcification. However, the cellular origins and fate of SPP1-associated VSMC populations remain incompletely understood. METHODS AND RESULTS: We generated a novel Spp1-rSTOPr-Cre (Spp1Cre) knock-in mouse line in which Cre recombinase is expressed from the endogenous Spp1 locus following Dre-mediated excision of a rox-flanked transcriptional STOP cassette. Correct targeting of the knock-in allele was validated by internal, 5' junction, 3' junction, and long-range PCR analyses, as well as Sanger sequencing. To establish an intersectional lineage-tracing strategy, Spp1Cre mice were crossed with Myh11DreERT2 and Rosa26-RSR-LSL-tdTomato-LSL-eGFP reporter mice, enabling permanent labeling of VSMC-derived populations following activation of the endogenous Spp1 locus. Under physiological conditions, eGFP-positive cells were detected at low frequency within the vascular wall and were predominantly negative for the contractile markers ACTA2 and MYH11. As a proof-of-principle application, eGFP-positive cells markedly expanded within atherosclerotic lesions induced by AAV-PCSK9D377Y and high-fat diet feeding. These lineage-traced cells remained largely ACTA2- and MYH11-negative, consistent with a modulated phenotype. Notably, only a minority of eGFP-positive cells expressed SPP1 or fibronectin at the time of analysis, demonstrating the utility of permanent lineage tracing for tracking cells with a history of endogenous Spp1 activation during vascular remodeling. CONCLUSION: We report the generation and validation of a novel Myh11Dre-Spp1Cre intersectional mouse model for lineage tracing of VSMC-derived populations that have activated the endogenous Spp1 locus. This genetic resource provides a valuable platform for investigating the origin, fate, and phenotypic evolution of Spp1-associated VSMC populations during vascular remodeling and cardiovascular disease.

Animals↗
PubMed1977

An autoradiographic study of smooth muscle hyperplasia in the swine ureter.

Autoradiographs of healing ureteral defects demonstrated significant uptake of tritiated thymidine in pigs sacrificed during the first 2 weeks after ureterotomy. The earliest and most heavily labeled tissue was epithelium followed by proliferation of subepithelial connective tissues and smooth muscle of the muscularis. The labeling of significant numbers of myocytes within the muscularis was indicative of smooth muscle replacement by hyperplastic means. The fact that most mitotically active smooth muscle cells were seen in the muscle remnant adjacent to wound margins suggests this as the primary source for new muscle.

Animals↗
PubMed1979

Primary myocardial disease in the diabetic mouse. An ultrastructural study.

The hearts from C57BL/KsJ db+/db+ mice and controls were examined by light and electron microscopy at intervals during 5 to 28 weeks of age. C57BL/6J ob/ob mice and their lean littermates served as other controls. The percentage of increase in body and heart weights of the diabetic animals was 150% and 64% greater, respectively, than that of the controls. Over the period of observation there was progressive damage to the ventricular myocytes and intramural small arteries and arterioles of the diabetic animals. Initially, the cardiac muscle cells of both ventricles contained large numbers of lipid droplets. Subsequently, there was shrinkage and increased electron density of mitochondria that were enveloped by single limiting membranes that in turn gave rise to large residual bodies. This was followed by loss of myofilaments and atrophy of myocytes. Similar changes occurred in the smooth muscle cells of intramural arteries and arterioles but not in those of epicardial arteries. Reduplicated layers of basal laminae were seen around interstitial capillaries. Degenerative changes also occurred in perivascular nerve endings. These changes are discussed in relation to the altered metabolism of the diabetic state. It is concluded that the pathologic lesions in the cardiac muscle cells and intramural arterial vessels and capillaries constitute a primary myocardial disease in the genetically diabetic mouse.

Animals↗
PubMed1976

[Reactivity of the smooth muscle tissue of the large intestine under conditions of experimental obstruction].

Morphohistochemical and autoradiographic techniques were used to study the reactivity of the large intestine tunica mascularis under experimental ileus. The smooth muscle cells are subjected to pronounced changes. At early terms (1-2 days) reactive-compensatory reactions are observed. They include increased metabolic processes, hypertrophy of myocytes, their increased synthetic and proliferative activity. Simultaneously there appear degenerative phonomena which become predominant on the 4th-6th days. The level of metabolism in the smooth muscle tissue drops and the synthetic and proliferative activity of myocytes decreases. They undergo atrophy and lyse.

Acid Phosphatase↗
PubMed1979

Comparative studies on the pre- and postterminal blood vessels in the cerebellar cortex of Rhesus monkey, cat, and rat.

In the rhesus monkey, cat and rat, pial arteries give off branches which run vertically through all three layers of the cerebellar cortex. The large cortical arteries are surrounded by a perivascular space in the molecular layer. Their wall consists of several layers of smooth-muscle cells and the luminal endothelium. As the arteries reach the deeper layers of the cerebellar cortex, the number of smooth-muscle cells is reduced. In the rat, sometimes no smooth-muscle cells are detectable in the preterminal arterial vessels. If these deep arteries branch off by dichotomy of terminal vessels there occurs a gradual or complete loss of myocytes in all three species. In the cat, where cortical arteries give off branches at right angles, there is a sphincter-like accumulation of smooth-muscle cells at the opening to the smaller branch. The postterminal vessels and veins in all species exhibit the same mural structure found in capillaries. The wall consists only of an endothelium and occasional pericytes embedded in the basal lamina. Even the large veins which run to the pial veins show this simple mural structure.

Animals↗
PubMed1976

[Hypertensive arteriopathy: aortic histo-metabolic changes during postnatal ontogenesis in spontaneous hypertensive rats (Okamoto-Aoki strain) (author's transl)].

27 aortic histoenzymatic activities and 6 aortic macromolecular substances were comparatively studied in spontaneous hypertensive rats (SHR) and normotensive Wistar rats (3, 5, 13 and 16 month-old). The earlier aortic changes (3rd month) were only histoenzymatic: 5 Nase and LDH were increased in the entire aorta: some oxido-reductases increase near the intima. These early minor changes might represent some of the factors of the functional disturbance of the arterial smooth muscle cell. At the stage of stable hypertension (5th-13th month) two lesion patterns were seen: 1) metabolic: increase of the histoenzymatic activities involved in lipolysis, GAG anabolism, glycolysis, cell respiration, energizing metabolism and nucleotides-esterolysis. 2) Structural: cell hypertrophy and hyperplasia, interstitial fibrosis. The stimulus of the metabolic changes seems to be dual: 1) the hypertensive factor acting upon smooth muscle cells and/or vasa vasorum. 2) The intraarterial pressure increasing endothelial crossing and stimulating myocyte contraction. The structural change is more probably the reaction to elevated pressure; it has led to diffuse medial thickening providing a balance between hypertension and arterial wall stress. On the 16th month, the cell reaction developed in two ways: 1) increase of metabolic and morphogenetic activation of some cells. 2) irreversible degeneration in some other cell groups (media necrosis, cicatricial fibrosis, decrease of oxidoreductases and lipolytic activities, increase of lysosomal enzymes). Aortic lesions during spontaneous hypertension were less dramatic and occurred later than after experimental hypertension. Some of the observed histometabolic changes might lead to maintenance and worsening of hypertension.

Animals↗
PubMed1978

Segmental differences in morphogenetic activity of arterial smooth muscle cells. Histochemical and radioautographic studies.

Differences in morphogenetic and metabolic activities of the arterial smooth muscle cells (s.m.c.) of the young rat's aorta and femoral artery were studied by histochemical, radiochemical and quantitative radioautographic methods. 3H-proline was found to be incorporated into the medial myocyte of both vessels and released into the extracellular connective tissue matrix during the first 6 hours. The intracellular and extracellular phases of this process were similar to those of other scleroprotein-synthesizing cells. The 3H-proline incorporation, the metachromasia (GAG) and the activities of acetyl-cholinesterase, beta-glucuronidase, aryl-sulfatase and 5'-nucleotidase were more intense in the aortic media. On the other hand, some oxido-reductases linked with cellular respiration, glycogenolysis and energy production as well as the myosin-ATPase and MAO activities are more intense in the femoral artery. These differences suggest the morpho-functional diversity of the arterial s.m.c.: greater morphogenetic activity of the aortic myocyte; earlier and higher contractile differentiation of the femoral one.

Animals↗
PubMed1978

[Effect of combined exposure to hypokinesia and gravitational stress on the structure of the wall of the renal vein].

Renal veins from 25 rabbits were investigated by means of imbedding in paraffin with subsequent hematoxylin--eosin staining, after Van Gieson and with fuchselin after Hart. Prolonged hypokinesia (over 3 weeks) with subsequent single application of gravitational overloading was stated to produce some structural changes in the wall of the renal vein. They are manifested as loosening of the middle vascular sheath with vacuolization of myocytes and outgrowth of its elastic elements. Hypokinesia of longer duration (8 weeks) with subsequent gravitational overloading produces atrophy of smooth muscle tissue in the middle sheath of the venous wall that brings about decreasing in tonus of the wall of the renal vein.

Animals↗
PubMed1975

[Some regularities of the regeneration of the musculature of internal organs].

The paper summarizes the data of the author and his co-workers on regulation of the musculature of vessels, digestive tract, uterus, ureters and urinary bladder. The smooth muscle cells have different degrees of differentiation. The muscular tissue of the vessels is most differentiated. The uterus musculature is very plastical. After injury mature myocytes are the first to undergo destruction. The intermedial substance is more stable. Myoblasts, young elements of the fibroblast row and the subendothelial layer cells are the origin of muscular regeneration. Figures of mitosis and amitosis are noted. Mature myocytes and intercellular substance are formed in the process of differentiation of the regeneration. The content of RNP in the regeneration cells is high, but in the process of differentiation of its elements it becomes lower. The DNP level has inconsiderable fluctuations. In early experiments PAS-positive substances are revealed in greater degree than in later ones. The content of acid mucopolysaccharides decreases in the process of fibrillogenesis. In all internal organs under study the muscular tissue regenerated. The degree of differentiation, severity of the lesion and functional peculiarities of the organ determine the completeness of the tissue reparation. The musculature of the intestinal tract and vessels regenerates more completely. Mighty layers of connective tissue with de novo formed blood vessels are disposed among the bundles of the repaired muscular tissue of the uterus and urine bladder wall. Simultaneously a part of regeneration cells are destroyed. These are two sides of a single process of development.

Animals↗
PubMed1979

Cellular pathology of homozygous familial hypercholesterolemia.

Tissues were studied from four subjects with homozygous familial hypercholesterolemia (FH). The specimens consisted of tissues obtained from a 20-week-old fetus at autopsy, samples from a 9-year-old girl during open-heart surgery, and biopsies of cutaneous xanthomas from a 13-year-old girl and a 21-year-old man. The FH fetus, but not the 3 control fetuses, exhibited multifocal lipid deposition particularly involving the stromal cells of the thymus, spleen, and skin and both the stromal and parenchymal cells of the kidney. Only one minute focus of intimal lipid accumulation was found in the aorta and coronary arteries of the FH fetus. A segment of the ascending aorta from the 9-year-old girl showed: 1) foam-cell transformation of many medial smooth-muscle cells, 2) abnormal vascularization of the inner media and intima, and 3) intimal involvement by a typical artherosclerotic plaque with lipid deposits in thin, elongated cells that showed some myocytic features and in foam cells that lacked such features. The mitral and aortic valves of this patient also contained numerous foam cells and showed mild to moderate fibrous thickening. A segment of the saphenous vein, however, contained no lipid deposits. The three xanthomas from two FH homozygotes exhibited marked lipid accumulation in histiocytic foam cells but no lipid deposits in the endothelium of blood vessels in the lesions. The findings in this study, in conjunction with those reported in studies of other FH homozygotes, indicate that homozygous FH is characterized by accelerated atherosclerosis and prominent lipid accumulation in macrophages and other stromal cells of the aortic and mitral valves, skin, tendon, and, varibly, in other extravascular sites. Since most of the intracellular lipid was in the form of non-membrane-bound neutral lipid droplets, it appears that the cytoplasm is the major site of lipid storage in this disease.

Adolescent↗
PubMed1977

The role of smooth muscle cells and hematogenous macrophages in atheroma.

Two types of lipid-containing cells were found in diet-induced atheromata of rabbits. The cells of the first type contained little acid esterase activity, were situated mainly in the deep and middle layers of the intima and constituted the overwhelming majority of foam cells. The lipid contained in them was bulky, indicating inefficient lipid emulsification and metabolism. The cells of the second type were rich in acid esterase activity and were situated in the superficial layer of the intima, often in subendothelial rows. These cells contained lipid which was finely emulsified and present in much smaller amounts than the lipid present in the first type of cell. The localisation of the two types of cells, the observation that only the second type of cell exhibited marked AS-D acetate esterase activity and the study of Adams and Bayliss (1976) indicate that, while the cells of the first type are myogenous, the cells of the second type are hematogenous macrophages. It is proposed that relative insufficiency of acid esterase activity in the myocytes is an important factor in the formation of atheroma. The intense acid esterase activity in the macrophages may play a major role in the healing of atheroma and its transformation into a fibrous plaque.

Animals↗