Activated nuclear factor-κB is present in the coronary vasculature in experimental hypercholesterolemia

Wilson, Stephanie H.; Caplice, Noel M.; Simari, Robert D.; Holmes, David R.; Carlson, Paula; Lerman, Amir

doi:10.1016/s0021-9150(99)00211-7

Cited by 122 publications

(68 citation statements)

References 29 publications

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“…The observed constitutive activation of NF-B by US28 is of potential pathophysiological relevance, as NF-B is an ubiquitously expressed transcription factor that plays a critical role in the regulation of inducible genes in immune response and inflammatory events associated with, for example, atherosclerosis (41)(42)(43). Activation of NF-B-mediated transcription has been reported in human aortic smooth muscle cells after CMV infection via PTX-sensitive G proteins.…”

Section: Resultsmentioning

confidence: 98%

Constitutive Signaling of the Human Cytomegalovirus-encoded Chemokine Receptor US28

Casarosa¹,

Bakker

Verzijl³

et al. 2001

Journal of Biological Chemistry

223

295

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Previously it was shown that the HHV-8-encoded chemokine receptor ORF74 shows considerable agonist-independent, constitutive activity giving rise to oncogenic transformation (Arvanitakis, L., Geras-Raaka, E., Varma, A., Gershengorn, M. C., and Cesarman, E. (1997) Nature 385, 347-350). In this study we report that a second viral-encoded chemokine receptor, the human cytomegalovirus-encoded US28, also efficiently signals in an agonist-independent manner. Transient expression of US28 in COS-7 cells leads to the constitutive activation of phospholipase C and NF-B signaling via G q/11 proteindependent pathways. Whereas phospholipase C activation is mediated via G␣ q/11 subunits, the activation of NF-B strongly depends on ␤␥ subunits with a preference for the ␤ 2 ␥ 1 dimer. The CC chemokines RANTES (regulated on activation, normal T cell expressed and secreted) and MCP-1 (monocyte chemotactic protein-1) act as neutral antagonists at US28, whereas the CX 3 C chemokine fractalkine acts as a partial inverse agonist with IC 50 values of 1-5 nM. Our data suggest that a high level of constitutive activity might be a more general characteristic of viral G protein-coupled receptors and that human cytomegalovirus might exploit this G protein-coupled receptor property to modulate the homeostasis of infected cells via the early gene product US28.

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Section: Resultsmentioning

confidence: 98%

Constitutive Signaling of the Human Cytomegalovirus-encoded Chemokine Receptor US28

Casarosa¹,

Bakker

Verzijl³

et al. 2001

Journal of Biological Chemistry

223

295

View full text Add to dashboard Cite

show abstract

“…3B), suggesting increased plaque vulnerability. Finally, we investigated the synergistic effect of DM and HC on the activation of the proinflammatory and prosurvival transcription factor NF-B, which is activated in atherogenesis (11,58). The results showed that while DM or HC alone had no effect on NF-B p65 activation, the combination of DM and HC resulted in a significant increase in enzyme activation (P Ͻ 0.05, Fig.…”

Section: Effects Of Hypophosphorylated Akt On Markers Of Inflammationmentioning

confidence: 96%

Akt pathway is hypoactivated by synergistic actions of diabetes mellitus and hypercholesterolemia resulting in advanced coronary artery disease

Hamamdzic

Fenning

Patel

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…24 This may stem from an increase of nuclear transcription factor-B (NF-B), which regulates many of the inflammatory vascular effects in hypercholesterolemia as well. 25 Arterial hypertension is perhaps the sturdiest stroke risk factor; accordingly, antihypertensives are most potent in stroke prevention. The association of chronically or acutely elevated blood pressure with markers of inflammation is well documented.…”

Section: Link Between Traditional Stroke Risk Factors and Inflammationmentioning

confidence: 99%

Inflammation and Infections as Risk Factors for Ischemic Stroke

Lindsberg

Grau

2003

Stroke

453

306

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Background-Inflammatory processes have fundamental roles in stroke in both the etiology of ischemic cerebrovascular disease and the pathophysiology of cerebral ischemia. We summarize clinical data on infection and inflammation as risk or trigger factors for human stroke and investigate current evidence for the hypothesis of a functional interrelation between traditional risk factors, genetic predisposition, and infection/inflammation in stroke pathogenesis. Summary of Review-Several traditional vascular risk factors are associated with proinflammatory alterations, including leukocyte activation, and predispose cerebral vasculature to thrombogenesis on inflammatory stimulation. Furthermore, accumulation of inflammatory cells, mainly monocytes/macrophages, within the vascular wall starts early during atherogenesis. During later disease stages, their activation can lead to plaque rupture and thrombus formation, increasing stroke risk. Inflammatory markers (eg, leukocytes, fibrinogen, C-reactive protein) are independent predictors of ischemic stroke. Chronic infections (eg, infection with Chlamydia pneumoniae or Helicobacter pylori) were found to increase the risk of stroke; however, study results are at variance, residual confounding is not excluded, and causality is not established at present. In case-control studies, acute infection within the preceding week was a trigger factor for ischemic stroke. Acute and exacerbating chronic infection may act by activating coagulation and chronic infections and may contribute to atherogenesis. Genetic predisposition of the inflammatory host response may be an important codeterminant for atherogenesis and stroke risk. Conclusions-Inflammation contributes to stroke risk via various interrelated mechanisms. Infectious diseases, traditional risk factors, and genetic susceptibility may cooperate in stimulating inflammatory pathways. Final proof of a causal role of infectious/inflammatory mechanisms in stroke pathogenesis is still lacking and will require interventional studies.

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Activated nuclear factor-κB is present in the coronary vasculature in experimental hypercholesterolemia

Cited by 122 publications

References 29 publications

Constitutive Signaling of the Human Cytomegalovirus-encoded Chemokine Receptor US28

Constitutive Signaling of the Human Cytomegalovirus-encoded Chemokine Receptor US28

Akt pathway is hypoactivated by synergistic actions of diabetes mellitus and hypercholesterolemia resulting in advanced coronary artery disease

Inflammation and Infections as Risk Factors for Ischemic Stroke

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