Antisense Oligonucleotides to the P65 Subunit of NF-κb Inhibit Human Vascular Smooth Muscle Cell Adherence and Proliferation and Prevent Neointima Formation in Rat Carotid Arteries

Autieri, M. V.; Yue, Tian‐Li; Ferstein, G. Z.; Eh, Ohlstein

doi:10.1006/bbrc.1995.2204

Cited by 124 publications

(73 citation statements)

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“…The measurement of activated NF-cB in surgical tissue may therefore serve as a useful prognostic tool to identify patients at high risk for thrombotic complications and restenosis. In addition, specific inhibition of NF-KB-related pathways may be a useful goal for future therapeutic intervention (Autieri, Yue, Feuerstein & Ohlstein, 1995).…”

Section: Conclusion and Further Implicationsmentioning

confidence: 99%

Role of nuclear factor‐kappa B in atherogenesis

Brand¹,

Page²,

Walli³

et al. 1997

Experimental Physiology

160

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Section: Conclusion and Further Implicationsmentioning
confidence: 99%

Role of nuclear factor‐kappa B in atherogenesis
Brand¹,
Page²,
Walli³
et al. 1997
Experimental Physiology
160
4
90
0
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“…Two additional studies showed that NF-B activity can produce vascular smooth muscle proliferation [248,249]. In one of these studies [248], antisense polynucleotides blocked expression of one of the protein subunits of NF-B and blocked vascular smooth muscle proliferation.…”

Section: Nf-bmentioning
confidence: 99%

“…In one of these studies [248], antisense polynucleotides blocked expression of one of the protein subunits of NF-B and blocked vascular smooth muscle proliferation. In the other study [249], a hyperactive mutant gene for the inhibitor of NF-B IkappaBalpha, greatly lowered NF-B activity and also blocked vascular smooth muscle proliferation.…”

Section: Nf-bmentioning
confidence: 99%

Pulmonary Hypertension Is a Probable NO/ONOO⁻ Cycle Disease: A Review
Pall
¹

2013
ISRN Hypertension
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16
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e NO/ONOO − cycle is a primarily local biochemical/physiological vicious cycle that appears to cause a series of chronic in�ammatory diseases. is paper focuses on whether the cycle causes pulmonary arterial hypertension (PAH) when located in the pulmonary arteries. e cycle involves 12 elements, including superoxide, peroxynitrite (ONOO − ), nitric oxide (NO), oxidative stress, NF-B, in�ammatory cytokines, iNOS, mitochondrial dysfunction, intracellular calcium, tetrahydrobiopterin depletion, NMDA activity, and TRP receptor activity. 10 of the 12 are elevated in PAH (NMDA?, NO?) and 11 have documented causal roles in PAH. Each stressor that initiates cases of PAH acts to raise cycle elements, and may, therefore, initiate the cycle in this way. PAH involves a primarily local mechanism as required by the cycle and the symptoms and signs of PAH are generated by elements of the cycle. Endothelin-1, which acts as a causal factor in PAH, acts as part of the cycle; its synthesis is stimulated by cycle elements, and it, in turn, increases each element of the cycle. is extraordinary �t to the principles of the NO/ONOO − cycle allows one to conclude that PAH is a NO/ONOO − cycle disease, and this �t supports the cycle as a ma�or paradigm of chronic in�ammatory disease.

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“…NF-B is a key transcriptional factor implicated in inflammation, and contributes to SMCs' ability to proliferate 121 . Therefore, NF-B activity was an important measure of inflammation in SMCs.…”

Section: Introductionmentioning
confidence: 99%

“…A variety of pro-inflammatory cytokines have been found in atherosclerotic plaques 121 . Pro-inflammatory cytokine expression is regulated by NF-B activity, which is highly regulated by atheroprone flow, PECAM, and FN 48 .…”

Section: Introductionmentioning
confidence: 99%

Mechanisms Regulating Smooth Muscle Cell Phenotype by Atheroprone and Atheroprotective Hemodynamics on Endothelial Cells
Boerboom
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Atherosclerosis is an inflammatory disease of the arteries that develops preferentially in regions where shear stress, caused by blood flowing within the lumen of the vessel, is disturbed. Recent evidence demonstrates focal fibronectin (FN) expression in the subendothelial layer in pre-atherosclerotic and advanced lesions. We have found that atheroprone shear stress promotes FN deposition and inflammatory signaling pathways in endothelial cells (ECs). Recently, our lab discovered that EC platelet endothelial cell adhesion molecule-1 (PECAM), which is important for sensing biomechanical stresses, is necessary for the production, secretion, and assembly of the FN-rich matrix in atheroprone regions.Similar to ECs, underlying vascular smooth muscle cells (SMCs) also display a proinflammatory phenotype in regions of atherogenesis, which is a key feature involved in the development of atherosclerosis. Our lab has designed a novel in vitro system that applies human-derived shear stresses to ECs, which are co-cultured with underlying SMCs. This allows for molecular manipulation of individual cell types, while permitting the study of the inherent signaling cross-talk between ECs and SMCs. Such an approach is useful because, while atheroprone shear stress is known to regulate EC signaling and promote a pro-inflammatory environment, the influence of that signaling on SMC phenotype has yet to be investigated.To assess the role of endothelial PECAM and FN signaling in promoting an inflammatory SMC phenotype, the co-culture model was exposed to atheroprone hemodynamic shear stress. siRNA knockdown of either PECAM or FN in ECs reduced SMC inflammatory genes, proteins, and transcription activity. The reduction in SMC inflammation also has the functional consequence of reducing monocyte adhesion. When EC FN is knocked down, the 4 inflammatory SMC phenotype was rescued through the addition of exogenous FN to the EC media. In addition to an increased inflammatory phenotype in response to atheroprone shear stress, SMCs are able to promote inflammation back to ECs. SMC FN was found to regulate EC inflammatory transcription activity and adhesion protein expression.Next, the role of secreted proteins in signaling inflammation from ECs under atheroprone shear stress to SMCs was determined. Cell media collected from EC PECAM and Finally, the atheroprotective role of Kruppel-like factor 4 (KLF4) in the endothelium was investigated. Anti-inflammatory and anti-thrombotic factors were previously shown to be under the regulation of the transcription factor KLF4. To study the role of KLF4 in establishing an atheroprotective phenotype, mono-cultured ECs were exposed to hemodynamic shear stress. KLF4 had increased expression under atheroprotective shear stress compared to atheroprone.Overexpression of KLF4 conferred an atheroprotective EC phenotype even when exposed to an atheroprone shear stress environment. In contrast, knockdown of EC KLF4 resulted in a proinflammatory and pro-thrombotic gene program despite exposure to atheroprotect...

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Antisense Oligonucleotides to the P65 Subunit of NF-κb Inhibit Human Vascular Smooth Muscle Cell Adherence and Proliferation and Prevent Neointima Formation in Rat Carotid Arteries

Cited by 124 publications

References 0 publications

Role of nuclear factor‐kappa B in atherogenesis

Role of nuclear factor‐kappa B in atherogenesis

Pulmonary Hypertension Is a Probable NO/ONOO⁻ Cycle Disease: A Review

Mechanisms Regulating Smooth Muscle Cell Phenotype by Atheroprone and Atheroprotective Hemodynamics on Endothelial Cells

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Antisense Oligonucleotides to the P65 Subunit of NF-κb Inhibit Human Vascular Smooth Muscle Cell Adherence and Proliferation and Prevent Neointima Formation in Rat Carotid Arteries

Cited by 124 publications

References 0 publications

Role of nuclear factor‐kappa B in atherogenesis

Role of nuclear factor‐kappa B in atherogenesis

Pulmonary Hypertension Is a Probable NO/ONOO− Cycle Disease: A Review

Mechanisms Regulating Smooth Muscle Cell Phenotype by Atheroprone and Atheroprotective Hemodynamics on Endothelial Cells

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Product

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Pulmonary Hypertension Is a Probable NO/ONOO⁻ Cycle Disease: A Review