Cardiovascular Events Associated with Long-Term Use of Celecoxib, Rofecoxib and Meloxicam in Taiwan

Huang, Weng Foung; Hsiao, Fei‐Yuan; Tsai, Yi Wen; Wen, Yue; Shih, Yaw Tang

doi:10.2165/00002018-200629030-00009

Cited by 32 publications

(12 citation statements)

References 15 publications

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“…Macrophages from Ind. COX-2 KOs revealed evidence consistent with substrate rediversion to the 5-lipoxygenase pathway with increased formation of their most abundant products, 5-HETE and LTC 4 . Thus, these mice may more closely correspond to those models described above in which 5-lipoxygenase induction accompanies further acceleration of atherosclerosis than observed with ApoE deficiency alone and in which the FLAP inhibitor MK 886 was effective.…”

Section: Discussionmentioning

confidence: 77%

“…Observational studies consistent with a cardiovascular risk have been reported for several traditional NSAIDs, which also exhibit selectivity for inhibition of COX-2, such as diclofenac and meloxicam (2)(3)(4)(5). The clinically manifest elements of this hazard (a predisposition to thrombotic events, an elevation of blood pressure, cardiac failure, and arrhythmogenesis) have been recapitulated in rodent models in which the COX-2-dependent formation of prostacyclin (PGI 2 ) or its action is disrupted (6)(7)(8).…”

mentioning

confidence: 78%

“…Pharmacological inhibition or genetic deletion of BLT1, a receptor of LTB 4 , restrains atherogenesis (40,41). Cysteine leukotrienes, LTC 4 and LTD 4 , induce concentration-dependent contractions in atherosclerotic coronary arteries (42). LTE 4 , the stable metabolite of LTC 4 , mediates pulmonary inflammation and platelet activation through the P2Y12 receptor (43).…”

Section: Discussionmentioning

confidence: 99%

“…Cysteine leukotrienes, LTC 4 and LTD 4 , induce concentration-dependent contractions in atherosclerotic coronary arteries (42). LTE 4 , the stable metabolite of LTC 4 , mediates pulmonary inflammation and platelet activation through the P2Y12 receptor (43). However, the importance of 5-lipoxygenase in atherogenesis has been debated.…”

Section: Discussionmentioning

confidence: 99%

“…Subsequent pairwise analysis revealed significant (P < 0.05) differences in the most abundant 5-lipoxygenase pathway products, 5-HETE and LTC 4 . Comparative P values obtained for LTB, LTD 4 , and LTE 4 are 0.055, 0.056, and 0.058, respectively. Error bars indicate SEM.…”

Section: Methodsmentioning

confidence: 97%

See 4 more Smart Citations

Disruption of the 5-lipoxygenase pathway attenuates atherogenesis consequent to COX-2 deletion in mice

Zhang

Crichton

Tang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Suppression of cyclooxygenase 2 (COX-2)–derived prostacyclin (PGI 2 ) is sufficient to explain most elements of the cardiovascular hazard from nonsteroidal antinflammatory drugs (NSAIDs). However, randomized trials are consistent with the emergence of cardiovascular risk during chronic dosing with NSAIDs. Although deletion of the PGI 2 receptor fosters atherogenesis, the importance of COX-2 during development has constrained the use of conventional knockout (KO) mice to address this question. We developed mice in which COX-2 was deleted postnatally, bypassing cardiorenal defects exhibited by conventional KOs. When crossed into ApoE-deficient hyperlipidemic mice, COX-2 deletion accelerated atherogenesis in both genders, with lesions exhibiting leukocyte infiltration and phenotypic modulation of vascular smooth muscle cells, as reflected by loss of α-smooth muscle cell actin and up-regulation of vascular cell adhesion molecule-1. Stimulated peritoneal macrophages revealed suppression of COX-2–derived prostanoids and augmented 5-lipoxygenase product formation, consistent with COX-2 substrate rediversion. Although deletion of the 5-lipoxygenase activating protein (FLAP) did not influence atherogenesis, it attenuated the proatherogeneic impact of COX-2 deletion in hyperlipidemic mice. Chronic administration of NSAIDs may increasingly confer a cardiovascular hazard on patients at low initial risk. Promotion of atherogenesis by postnatal COX-2 deletion affords a mechanistic explanation for this observation. Coincident inhibition of FLAP may offer an approach to attenuating such a risk from NSAIDs.

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Section: Discussionmentioning

confidence: 77%

mentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 97%

See 3 more Smart Citations

Disruption of the 5-lipoxygenase pathway attenuates atherogenesis consequent to COX-2 deletion in mice

Zhang

Crichton

Tang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Veterinary Adverse Reactions and Crisis Management

Woodward¹

2009

Veterinary Pharmacovigilance

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Celecoxib decreases mitochondrial complex IV activity and induces oxidative stress in isolated rat heart mitochondria: An analysis for its cardiotoxic adverse effect

Atashbar

Jamali

Khezri

et al. 2021

J Biochem & Molecular Tox

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In spite of the cardiotoxic effect of selective cyclooxygenase-2 inhibitors, they are most widely used as anti-inflammatory and analgesic drugs. Today, valdecoxib and rofecoxib have been withdrawn in the market but celecoxib remains.In this study, we focused on an analysis of celecoxib toxic effects on isolated mitochondria. Isolated rat heart mitochondria were obtained using differential centrifugation. Using flow cytometry and biochemical assays, we searched succinate dehydrogenases, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) formation, mitochondrial swelling, ATP/ADP ratio, lipid peroxidation, and mitochondrial complexes activity in rat heart isolated mitochondria. Herein, our results indicated a significant decrease in the activity of complex IV after exposure with celecoxib (16 µg/ml). This decrease in the activity of complex IV is paralleled by the MMP collapse, ROS formation, mitochondrial swelling, depletion of ATP, and lipid peroxidation. For the first time, this introductory study has shown a significant decrease in the activity of complex IV and mitochondrial dysfunction after exposure with celecoxib in rat heart isolated mitochondria.

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Cardiovascular Events Associated with Long-Term Use of Celecoxib, Rofecoxib and Meloxicam in Taiwan

Cited by 32 publications

References 15 publications

Disruption of the 5-lipoxygenase pathway attenuates atherogenesis consequent to COX-2 deletion in mice

Disruption of the 5-lipoxygenase pathway attenuates atherogenesis consequent to COX-2 deletion in mice

Veterinary Adverse Reactions and Crisis Management

Celecoxib decreases mitochondrial complex IV activity and induces oxidative stress in isolated rat heart mitochondria: An analysis for its cardiotoxic adverse effect

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