scholarly journals DNA Fragmentation and Ultrastructural Changes of Degenerating Cells in Atherosclerotic Lesions and Smooth Muscle Cells Exposed to Oxidized LDL in Vitro

1997 ◽  
Vol 17 (10) ◽  
pp. 2225-2231 ◽  
Author(s):  
Stefan Jovinge ◽  
Milita Crisby ◽  
Johan Thyberg ◽  
Jan Nilsson
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Dna Fragmentation ◽  
Oxidized Ldl ◽  
Muscle Cells ◽  
Ultrastructural Changes ◽  
Atherosclerotic Lesions

Abstract 581: Smooth Muscle Cell Specific Loss of the Pluripotency Factor Oct4 Enhances Atherosclerosis via Shifting Smooth Muscle Cells to a Less Migratory, but More Proinflammatory Phenotype

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Olga A Cherepanova ◽  
Gabriel Falcao Alencar ◽  
Svyatoslav M Tkachenko ◽  
Stefan Bekiranov ◽  
Gary K Owens
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
High Fat Diet ◽  
Oxidized Ldl ◽  
Muscle Cells ◽  
Lineage Tracing ◽  
High Fat ◽  
Fibrous Cap ◽  
Pluripotency Factor

Atherosclerosis is the leading cause of death in Western civilization accounting for more than 40% of all deaths. Despite reduced death rates due in part to statin treatment, there is little understanding of the molecular and cellular mechanisms that can help to reverse atherosclerotic development and/or decrease the chances of plaque rupture with associated clinical sequelae such as myocardial infarction or stroke. We recently demonstrated a functional role of the pluripotency factor OCT4 in smooth muscle cells (SMCs) during atherosclerosis, in that SMC-specific conditional Oct4 knockout mice exhibit marked alterations in lesion size and cellular composition within atherosclerotic lesions of Apoe -/- high-fat diet fed mice, including a thinner fibrous cap, increased necrotic core and increased intra-plaque hemorrhage. Results of SMC-lineage tracing studies show that these changes were likely due to marked reductions in SMC number within lesions including in the fibrous cap area, as well as significant increases in macrophage-like (LGALS3 + ) SMCs within the tunica media. Further studies show that inactivation of Oct4 in SMCs nearly completely abrogated the pro-atherogenic oxidized phospholipid POVPC-induced migration of SMCs in vitro and outgrowth of SMCs from aortic explants ex vivo. RNA-seq and ChIP-seq analyses of lesion specimens from Apoe -/- high-fat diet fed mice and cultured SMCs treated with POVPC or 1% O 2 hypoxia show that loss of Oct4 in SMCs was associated with marked activation of genes associated with inflammation and phagocytosis, and suppression of genes associated with cell migration, including extracellular matrix proteins, matrix metalloproteinases and multiple axon guidance molecules. Moreover, loss of Oct4 significantly increased ability of SMCs to phagocyte red blood cells in response to oxidized LDL treatment in vitro . Results advance our understanding of mechanisms by which OCT4 expression in SMCs impacts atherosclerosis lesion development and may help identify novel potential therapeutic targets for treatment of atherosclerosis.

scholarly journals CARMN Loss Regulates Smooth Muscle Cells and Accelerates Atherosclerosis in Mice

2021 ◽  
Author(s):  
Francesca Vacante ◽  
Julie Rodor ◽  
Mukesh K Lalwani ◽  
Amira D Mahmoud ◽  
Matthew Bennett ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Molecular Mechanisms ◽  
Muscle Cells ◽  
Vascular Pathology ◽  
Critical Event ◽  
Knock Out ◽  
Atherosclerotic Lesions

Rationale: In the microenvironment of atherosclerotic lesions, vascular smooth muscle cells (vSMCs) switch to a dedifferentiated state but the underlying molecular mechanisms driving this switch are not fully understood. Long noncoding RNAs (lncRNAs) are dysregulated during vascular pathology, but relatively little is known about their involvement in controlling vSMCs function. CARMN is a lncRNA located immediately upstream of the microRNAs (miRNAs) miR-143 and miR-145, both involved in vSMCs function. Objective: We investigated the role of the lncRNA CARMN, independent from miR-143 and miR-145, as potential a regulator of vSMC phenotypes in vitro and the consequences of its loss during the development of atherosclerosis in vivo. We hypothesized that loss of CARMN is a primary event controlling the functional switch towards pro-atherogenic vSMC phenotype and accelerates the development of the plaques in vivo. Methods and Results: Expression of CARMN lncRNA was silenced using GapmeRs in human coronary arterial smooth muscle cells (hCASMCs), revealing that GapmeR-mediated loss of CARMN negatively affects miR-143 and miR-145 miRNA expression. RNA sequencing of CARMN-depleted hCASMCs revealed large transcriptomic changes, associated with vSMC proliferation, migration, inflammation, lipid metabolism and dedifferentiation. The use of miR-143 and miR-145 mimics revealed that CARMN regulates hCASMC proliferation in a miRNA-independent manner. In human and mouse, CARMN and associated miRNAs were downregulated in advanced versus early atherosclerotic lesions. Using a CRISPR-Cas9 knock-out approach, we explored the implications of CARMN depletion during atherosclerosis in vivo. Consistent with in vitro results, the knock-out of CARMN impaired the expression of miR-143 and miR-145 under homeostatic conditions. Importantly, when atherosclerosis was induced in these mice, CARMN knock-out increased the volume, size, pro-inflammatory LGALS3-expressing cells content and altered plaque composition, yielding an advanced phenotype. Conclusions: We identified the early loss of CARMN lncRNA as critical event which primes vSMCs towards a pro-atherogenic phenotype in vitro and accelerates the development of atherosclerosis in vivo.

Epicardial Cells of Human Adults Can Undergo an Epithelial-to-Mesenchymal Transition and Obtain Characteristics of Smooth Muscle Cells In Vitro

Stem Cells ◽  
2007 ◽  
Vol 25 (2) ◽  
pp. 271-278 ◽  
Author(s):  
John van Tuyn ◽  
Douwe E. Atsma ◽  
Elizabeth M. Winter ◽  
Ietje van der Velde-van Dijke ◽  
Daniel A. Pijnappels ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Muscle Cells ◽  
Mesenchymal Transition ◽  
Epicardial Cells ◽  
Human Adults

Characterization and confocal imaging of calponin in gastrointestinal smooth muscle

1993 ◽  
Vol 265 (5) ◽  
pp. C1371-C1378 ◽  
Author(s):  
M. P. Walsh ◽  
J. D. Carmichael ◽  
G. J. Kargacin
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
Thin Filament ◽  
Muscle Cells ◽  
Biochemical Properties ◽  
Confocal Imaging ◽  
Isolated Cells ◽  
Independent Manner

Calponin isolated from chicken gizzard smooth muscle binds in vitro to actin in a Ca(2+)-independent manner and thereby inhibits the actin-activated Mg(2+)-adenosinetriphosphatase of smooth muscle myosin. This inhibition is relieved when calponin is phosphorylated by protein kinase C or Ca2+/calmodulin-dependent protein kinase II, suggesting that calponin is involved in thin filament-associated regulation of smooth muscle contraction. To further examine this possibility, calponin was isolated from toad stomach smooth muscle, characterized biochemically, and localized in intact isolated cells. Toad stomach calponin had the same basic biochemical properties as calponin from other sources. Confocal immunofluorescence microscopy revealed that calponin in intact smooth muscle cells was localized to long filamentous structures that were colabeled by antibodies to actin or tropomyosin. Preservation of the basic biochemical properties of calponin from species to species suggests that these properties are relevant for its in vivo function. Its colocalization with actin and tropomyosin indicates that calponin is associated with the thin filament in intact smooth muscle cells.

Light and dark smooth muscle cells in estrogen-stimulated rat myometrium

1976 ◽  
Vol 54 (6) ◽  
pp. 822-833 ◽  
Author(s):  
R. E. Garfield ◽  
E. E. Daniel
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Atp Depletion ◽  
Metabolic Inhibitors ◽  
Volume Control ◽  
Control Mechanisms ◽  
Dark Cells ◽  
Light Cells

Smooth muscle cells of different densities to transmission of electrons (termed light and dark cells) were found in rat myometrium examined in the electron microscope following fixation by immersion in glutaraldehyde. Light cells accounted for about 4% of the total population of cells. No light cells were found in tissues fixed in situ by intraarterial perfusion with glutaraldehyde. In addition to staining differences, light cells were distinguished from most dark cells by differences in nuclear, mitochondrial, endoplasmic reticular, and surface structures. The relative number of light and dark cells after in vitro fixation was not changed in tissues relaxed with adrenaline or contracted with oxytocin. Mechanical injury resulted in increased numbers of light cells. Similarly, chemical injury with metabolic inhibitors resulted in ATP depletion, followed by increased numbers of light cells and gain in water content. We concluded that light cells were produced by mechanical or metabolic damage, leading to loss of volume control mechanisms, swelling, and leakage of protein. Light cells found after fixation in vitro in numerous prior studies represent cells damaged during isolation, and not a physiological variant among smooth muscle cells.

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