Faculty Opinions recommendation of Integrin beta3 regulates clonality and fate of smooth muscle-derived atherosclerotic plaque cells.

2018 ◽  
Author(s):  
Stephen Schwartz
Keyword(s):  
Smooth Muscle ◽  
Atherosclerotic Plaque ◽  
Integrin Beta3

scholarly journals Integrin beta3 regulates clonality and fate of smooth muscle-derived atherosclerotic plaque cells

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Ashish Misra ◽  
Zhonghui Feng ◽  
Rachana R. Chandran ◽  
Inamul Kabir ◽  
Noemi Rotllan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Atherosclerotic Plaque ◽  
Integrin Beta3

Processing of Chimeric Antisense Oligonucleotides by Human Vascular Smooth Muscle Cells and Human Atherosclerotic Plaque

Circulation ◽  
1996 ◽  
Vol 93 (4) ◽  
pp. 772-780 ◽  
Author(s):  
J. Geoffrey Pickering ◽  
Jeffrey M. Isner ◽  
Carol M. Ford ◽  
Lawrence Weir ◽  
Andrew Lazarovits ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Atherosclerotic Plaque ◽  
Antisense Oligonucleotides ◽  
Muscle Cells ◽  
Human Atherosclerotic Plaque

Abstract 102: Cd98 Modulates Atherosclerotic Plaque Morphology by Regulating Smooth Muscle Cell Proliferation via the P-38 Map Kinase Pathway

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Sara McCurdy ◽  
Yvonne Baumer ◽  
Franz Hess ◽  
William A Boisvert
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Atherosclerotic Plaque ◽  
Necrotic Core ◽  
Plaque Morphology ◽  
Fibrous Cap ◽  
Plaque Area

Smooth muscle cells (SMC) are known to migrate and proliferate to form a stabilizing fibrous cap that encapsulates atherosclerotic plaques. It has been shown that CD98hc, a transmembrane protein with a known role in amino acid transport and integrin signaling, is involved in proliferation and survival of various cell types including SMC. Based on these data, we hypothesized that CD98hc deficiency selectively in SMC would have pathogenic effects on atherosclerosis development and plaque composition. To test this, we utilized mice with SMC-specific deletion of the CD98hc ( CD98hc fl/fl SM22Cre + ) to determine the effects of CD98hc deficiency on SMC function in the context of atherosclerosis. We performed in vitro proliferation and survival/apoptosis assays to investigate the role of CD98hc in the proliferation and survival of primary mouse aortic vascular smooth muscle cells. We found that VSMC isolated from whole aortas of CD98hc -/- animals displayed approximately 60% reduced cell counts compared to control (41 ± 8.2% of control) after 5 days in culture. EdU assays in vivo showed a defect in the ability of CD98hc -/- SMC to proliferate, with 25% reduction in EdU-positive VSMC compared to controls (2.3 ± 0.2% vs 3 ± 0.2%). In addition, caspase-3 staining of SMC in vitro displayed a 41% increase in propensity of CD98hc -/- SMC to undergo apoptosis compared to controls (7.9 ± 0.6% vs 5.6 ± 0.5%). Furthermore, the absence of CD98hc in SMC caused a sharp increase in phosphorylated p-38, which was partially abrogated towards control levels when the cells were treated with PDGF-BB to induce proliferation. Long-term atherosclerosis study using SMC-CD98hc -/- /LDLR -/- mice showed that atherosclerotic plaque morphology was altered with increased necrotic core area (25.8 ± 1.9% vs 10.9 ± 1.6% necrotic core area per plaque area) due to a reduction in infiltration of SMC within the plaque (2.1 ± 0.4% vs 4.3 ± 0.4% SM22α positive area per plaque area) compared to control LDLR -/- mice. These data support an important role for CD98hc and its regulation of p-38 MAP kinase signaling in aortic vascular smooth muscle cell proliferation and survival. We conclude that CD98hc is critical for the formation of fibrous cap that is important in maintaining the stability of atherosclerotic plaque.

Abstract 381: IL-19 Inhibits Atherosclerosis in LDLR-/- Mice by Modulating Cholesterol Uptake in Macrophages and Vascular Smooth Muscle Cells

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Khatuna Gabunia ◽  
Stephen P Ellison ◽  
James M Richards ◽  
Sheri E Kelemen ◽  
Michael V Autieri
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Atherosclerotic Plaque ◽  
Scavenger Receptor ◽  
Muscle Cells ◽  
Wild Type ◽  
Anti Inflammatory ◽  
M2 Phenotype

IL-19 is a recently described, putative anti-inflammatory cytokine which had previously been ascribed to be leukocyte specific. IL-19 is not detected in normal artery, but we detected IL-19 in multiple cell types in human atherosclerotic plaque suggesting a role for this interleukin in atherosclerosis. The purpose of this study was to determine whether administration of exogenous IL-19 could attenuate development of pre-formed atherosclerotic plaque, and to identify potential molecular mechanisms. LDLR-/- mice were fed high-fat diet for 12 weeks and then administered with 10ng/g/day IL-19 or PBS for an additional 8 weeks. En face analysis demonstrated that IL-19 could halt, but not reverse existing plaque (26.7+/-1.7%, 41.03+/-3.1%, 23.70+/-2.6% for baseline, PBS control, and IL-19-treated mice). Foam cell formation by macrophages and vascular smooth muscle cells (VSMC) is a hallmark event during atherosclerosis. Nothing has been reported regarding IL-19 effects on macrophage or VSMC lipid uptake; we therefore investigated whether IL-19 affects macrophage and VSMC cholesterol handling. Addition of IL-19 to wild-type bone marrow derived macrophages (BMDM) significantly promoted oxLDL uptake, conversely, BMDM from IL-19-/- mice had significantly less oxLDL uptake compared to wild-type BMDM. Addition of IL-19 to wild type BMDM significantly increased expression of scavenger receptor B1 (SR-B1), and decreased expression of inflammatory cytokines TNFα, IL-12b, MCP1. Interestingly, converse results were obtained with VSMC, as addition of IL-19 to wild-type VSMC decreased uptake of oxLDL ( p<0.05 ) and decreased expression of scavenger receptor CD36. VSMC isolated from IL-19-/- mice had increased uptake of oxLDL (p<0.0001). It is reported that M2 macrophages participate in plaque regression. IL-19 decreased IL-12b and significantly promoted the polarization of anti-inflammatory M2 phenotype in BMDM as evidenced by the increased expression of YM1 and IL-10 mRNA. These data demonstrate that IL-19 can inhibit progression of existing atherosclerotic plaque by modulating lipid metabolism in VSMC and macrophages and by promoting macrophage differentiation into an alternative, anti-inflammatory M2 phenotype.

Abstract 46: The Effects of Membrane Cholesterol on Vascular Smooth Muscle Cell Stiffness and Adhesion to Fibronectin

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Josh Childs ◽  
Zhongkui Hong Hong
Keyword(s):  
Smooth Muscle ◽  
Cell Membrane ◽  
Vascular Smooth Muscle ◽  
Atherosclerotic Plaque ◽  
Adhesion Force ◽  
Foam Cells ◽  
Sensory Function ◽  
Cell Stiffness ◽  
Membrane Cholesterol ◽  
Cholesterol Depletion

Atherosclerosis remains a major cause of cardiovascular disease (CVD). Cholesterol has been identified as a major contributor to the cause of atherosclerosis. It is well known that the cholesterol accumulation in macrophage-derived foam cells is the major component of atherosclerotic plaque. However, growing evidences suggests that cholesterol loading into vascular smooth muscle cells (VSMC) in atherosclerosis is much larger than previously known, and about 40% of total foam cells in the atherosclerotic plaque are VSMC-derived. Cholesterol may not only contribute as the fatty deposition in the atherosclerotic lesion, but also play a critical role in the VSMC migration toward the intima of the blood vessel wall. In addition, the arterial wall becomes stiffer during atherosclerosis altering the micromechanical environment experienced by the VSMCs leading to changes in VSMC stiffens, adhesion, and phenotype. Migration of VSMCs is a complex process including proliferation and phenotypic switching of VSMCs, thus contributing too many changes in cell membrane adhesion molecules. We tested the hypothesis that membrane cholesterol in VSMCs may play an important role in α 5 β 1 -integrin mediated adhesion, and alter the sensory function of VSMCs to ECM mechanical properties. In this study cholesterol manipulation was achieved using methyl-β-cyclodextrin, and gel substrates with varying stiffness were used to mimic the changing environment in atherosclerosis. Atomic force microscopy (AFM) was used to determine integrin-fibronectin adhesion force and cell stiffness. A custom-written MATLAB program was used to interpret the elasticity of the VSMC cytoskeleton and adhesion force. Cellular adhesion was measured for 50%-70% confluent cells with a sample size of 50 cells on a fibronectin coated AFM stylus probe. Our results show that there is a significant decrease in α5β1-integrin adhesion of VSMCs on substrates above 9 kPa upon membrane cholesterol depletion. Additionally, mechanotransduction of VSMCs upon cholesterol depletion is less efficient. In conclusion, cell membrane cholesterol and extracellular mechanical signals may synergistically regulate cellular mechanical functions of VSMCs and their migration in the progression of atherosclerosis.

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