Cyclooxygenase-2 inhibition increases lipopolysaccharide-induced atherosclerosis in mice

Gitlin, Jonathan M.; Loftin, Charles D.

doi:10.1093/cvr/cvn286

Cited by 60 publications

(44 citation statements)

References 33 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Additionally, the dampened HPA response in indomethacin-treated animals likely reduced glucocorticoid inhibition of inflammatory cytokine production resulting in widespread increases in inflammatory cytokine production. These data are of particular interest because nonsteroidal anti-inflammatory drugs are commonly used for the relief of pain and inflammation, yet chronic use is associated with an increased risk of atherosclerosis and thrombosis (6,25,28). It is possible that COX inhibitors create a prothrombotic state by elevating proinflammatory cytokines responses, which upregulate adhesion molecules on endothelial cells promoting leukocyte adhesion and aggregation to vessel walls and increase the production of tissue factor while simultaneously preventing the formation of PGI 2 that typically inhibit proinflammatory cytokine production (44,64) as well as platelet activation (7) and aggregation (4,9,29,33,42).…”

Section: R1653 Time-dependent Mediators Of the Hpa Axis Following E mentioning

confidence: 99%

Time-dependent mediators of HPA axis activation following live Escherichia coli

Zimomra

Porterfield

Camp

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Zimomra ZR, Porterfield VM, Camp RM, Johnson JD. Time-dependent mediators of HPA axis activation following live Escherichia coli . Am J Physiol Regul Integr Comp Physiol 301: R1648-R1657, 2011. First published September 14, 2011 doi:10.1152/ajpregu.00301.2011.-The hypothalamus-pituitary-adrenal (HPA) axis is activated during an immune challenge to liberate energy and modulate immune responses via feedback and regulatory mechanisms. Inflammatory cytokines and prostaglandins are known contributors to HPA activation; however, most previous studies only looked at specific time points following LPS administration. Since whole bacteria have different immune stimulatory properties compared with LPS, the aim of the present studies was to determine whether different immune products contribute to HPA activation at different times following live Escherichia coli challenge. Sprague-Dawley rats were injected intraperitoneally with E. coli (2.5 ϫ 10 7 CFU) and a time course of circulating corticosterone, ACTH, inflammatory cytokines, and PGE2 was developed. Plasma corticosterone peaked 0.5 h after E. coli and steadily returned to baseline by 4 h. Plasma PGE2 correlated with the early rise in plasma corticosterone, whereas inflammatory cytokines were not detected until 2 h. Pretreatment with indomethacin, a nonselective cyclooxygenase inhibitor, completely blocked the early rise in plasma corticosterone, but not at 2 h, whereas pretreatment with IL-6 antibodies had no effect on the early rise in corticosterone but attenuated corticosterone at 2 h. Interestingly, indomethacin pretreatment did not completely block the early rise in corticosterone following a higher concentration of E. coli (2.5 ϫ 10 8 CFU). Further studies revealed that only animals receiving indomethacin prior to E. coli displayed elevated plasma and liver cytokines at early time points (0.5 and 1 h), suggesting prostaglandins suppress early inflammatory cytokine production. Overall, these data indicate prostaglandins largely mediate the early rise in plasma corticosterone, while inflammatory cytokines contribute to maintaining levels of corticosterone at later time points.corticosterone; prostaglandin; IL-6; indomethacin ACTIVATION OF THE hypothalamus-pituitary-adrenal (HPA) axis is one of the critical brain-mediated sickness responses that enhance survival of an organism during an immune challenge. The resulting elevation in circulating glucocorticoids, mainly cortisol in humans and corticosterone in mice and rats, liberate energy necessary to mount a fever and have numerous immunomodulatory effects that reduce the risk of septic shock and increase the chances of survival during infection (52, 53). For example, glucocorticoids suppress proinflammatory cytokines (2, 17, 34) and prostaglandin production (27, 38), stimulate anti-inflammatory cytokine production (16, 20), upregulate Fc receptors and major histocompatibility complex class II molecules on phagocytes (24), increase cell adhesion molecules on endothelial cells (57), enhance acute phase changes in t...

show abstract

Section: R1653 Time-dependent Mediators Of the Hpa Axis Following E mentioning

confidence: 99%

Time-dependent mediators of HPA axis activation following live Escherichia coli

Zimomra

Porterfield

Camp

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…Several studies have reported that repeated injections of endotoxin in animals significantly accelerates atherosclerosis, suggesting that LPS-induced immune mechanisms play an important role in the atherosclerotic process 5,23,24) . The findings of the present study are consistent with those of the above studies, although they are in direct contrast with the results of earlier studies in which no proatherogenic effects of endotoxin administration were observed in piglets or rabbits fed a high-cholesterol diet 25,26) .…”

Section: Discussionmentioning

confidence: 99%

“…One potentially important source of inflammation is endotoxin. Previous studies have indicated a relationship between endotoxin and atherosclerosis 5,6) . In the present study, a simple rabbit model of LPS-induced spontaneous carotid atherosclerotic thrombosis was established using a cholesterol-enriched diet and balloon injury to the target artery.…”

Section: Oct Image Analysismentioning

confidence: 94%

“…Inflammation plays an important role in the generation and development of atherosclerotic plaque. Lipopolysaccharide (LPS), a potent endotoxin, is a potentially important source of inflammation 5,6) . The purpose of the present study was to establish a rabbit model of spontaneous carotid plaque disruption, erosion and LPS-induced secondary thrombosis.…”

Section: Oct Analysismentioning

confidence: 99%

See 1 more Smart Citation

A Rabbit Model of Spontaneous Thrombosis Induced by Lipopolysaccharide

Liu

Hou

et al. 2014

JAT

View full text Add to dashboard Cite

Aim: Inflammation plays a critical role in the development of atherosclerotic plaque, and lipopolysaccharide (LPS) is a potentially important source of inflammation. The aim of this study was to develop a rabbit model of spontaneous thrombosis mimicking the pathophysiological and morphological characteristics of atherosclerotic plaque in humans. Methods: The rabbits were randomized into four groups: group A (n = 10) received a normal diet; group B (n = 10) received a regular diet and weekly LPS injections (1 μg/kg, Escherichia coli); group C (n = 15) received a cholesterol-enriched diet before and after sustaining a balloon injury to the right common carotid artery; and group D (n = 15) was treated the same as group C in addition to receiving LPS injections. The morphological characteristics of the resulting lesions were evaluated using optical coherence tomography (OCT) and histology. Results: No significant atherosclerotic plaque was observed in groups A or B. Group D exhibited a higher incidence of spontaneous luminal thrombi than group C or B (60% vs. 20% vs. 10%, p＜ 0.05). All of the thrombi detected with OCT were confirmed on histology. A good correlation between the fibrous cap thickness and thrombus arc was obtained on OCT and the histological evaluations. Conclusions: A rabbit model of LPS-induced spontaneous thrombosis was developed in which OCT was used to follow changes in plaque morphology.

show abstract

“…Semakin kuat intensitas warna semakin kuat ekspresi COX-2. Hal ini sesuai dengan hasil penelitian 15 bahwa protein COX-2 terekspresi pada sel inflamasi, sel endotel, fibroblas gingiva dan sel epitel pada gingiva yang terinflamasi.…”

Section: Pembahasanunclassified