Cardiovascular effects of cyclooxygenase‐2 inhibitors: a mechanistic and clinical perspective

Patrono, Carlo

doi:10.1111/bcp.13048

Cited by 129 publications

(82 citation statements)

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“…Cyclooxygenase-2 (COX-2) is an inflammatory signal-induced key enzyme in arachidonic acid metabolism, being induced in normal cell types, including blood-derived macrophages, microglia, and endothelial cells in response to inflammatory cytokines (Patrono, 2016). COX-2 expression in ischemic tissue is quickly up-regulated after tMCAO together with MMP-2 and MMP-9 activity.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory cell populations in early neuroinflammation in the core and peri-ischemic lesions of rat brain after transient focal cerebral ischemia: A morphometric study

Horváth

Orădan

Chiriac

et al. 2018

Preprint

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Background and Objective:Clinical and experimental observations emphasize the role of inflammation as a direct risk factor for stroke. To better characterize the inflammation, we have conducted a detailed histological analysis of the inflammatory cell population after transient middle cerebral artery occlusion in a rat model. Methods:Fifteen adult Wistar male rats were divided randomly into test (n=10) and sham (n=5) groups. In the ischemic group, transient focal cerebral ischemia was induced with an intraluminal filament technique. Histologic lesions of the ischemic core and the surrounding penumbra zone were evaluated, based on a complex algorithm. Representative morphological changes in the core and the penumbra zone were compared. Immunohistochemistry was performed for leukocytes markers (CD15, CD68, CD3), leukocyte-released effectors (MMP-9 and COX-2), and FXIII (possibly involved in microglia and macrophage activation)Results: Neuronal vacuolation and degeneration were significantly more in the core lesion, whereas cellular edema and inflammatory infiltrate were increased in the penumbra. CD68, CD3, FXIII and Cox-2 expression were significantly higher in the penumbra than in the core (p=0.026; p=0.006; p=0.002; and p<0.001).Discussion: In the rat model of middle cerebral artery occlusion, inflammatory mechanisms, microglia/macrophage cells, and T-lymphocytes likely play an important role in the penumbra. The deterioration of neurons is less in the penumbra than in the core. Appreciation of the role of the inflammatory cells and mechanisms involved in stroke might lead to measures to inhibit the injury and save brain volume. ABSTRACT Background and Objective: Clinical and experimental observations emphasize the role of inflammation as a direct risk factor for stroke. To better characterize the inflammation, we have conducted a detailed histological analysis of the inflammatory cell population after transient middle cerebral artery occlusion in a rat model.

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Section: Discussionmentioning

confidence: 99%

Inflammatory cell populations in early neuroinflammation in the core and peri-ischemic lesions of rat brain after transient focal cerebral ischemia: A morphometric study

Horváth

Orădan

Chiriac

et al. 2018

Preprint

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“…This is the first demonstration in a large, randomized, double‐blind, placebo‐controlled phase III study that using anti‐cytokine‐based therapies may be a viable approach for secondary prevention of atherosclerosis‐related CVD. This is particularly relevant given that the use of traditional non‐steroidal anti‐inflammatory drugs and coxibs alike is limited by cardiovascular toxicity, as comprehensively discussed by Patrono (). He provides an overview of the cardiovascular effects of COX‐2 inhibitors, with a focus on the mechanisms contributing to the clinical readouts of COX‐2 inhibition.…”

Section: Nomenclature Of Targets and Ligandsmentioning

confidence: 99%

Targeting inflammation to reduce cardiovascular disease risk

Maffia

Cirino

2017

British J Pharmacology

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This joint themed section of the British Journal of Pharmacology and the British Journal of Clinical Pharmacology stems from a joint British Pharmacological Society -Italian Society of Pharmacology symposium held at the 37 th National Congress of the Italian Society of Pharmacology in Naples (Italy) from 27 to 30 October 2015. LINKED ARTICLESThis article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/ 10.1111/bcp.v82.4/issuetoc Abbreviations AT, adipose tissue; ATL, aspirin-triggered lipoxin A4; CVDs, cardiovascular diseases Cardiovascular diseases (CVDs) are the major cause of morbidity and mortality in Western society and, in the near future, are expected to be the main cause of death globally (WHO, 2011). Basic research data strongly support a crucial role played by inflammatory and immune mechanisms in CVD, and studies in animal models have shown that specific immune-inflammatory pathways could be targeted for therapeutic utility. However, the translation of this scientific knowledge to the treatment of human CVDs is still in the early stages (Welsh et al., 2017).New and selective immune therapies are already in use for the treatment of autoimmune diseases, and large clinical trials have just been published or are currently evaluating the effect of several of these treatments on atherosclerosis and related pathologies. The outcome of these studies is likely to lead to new approaches in the management of vascular inflammation.This joint themed section of the British Journal of Pharmacology and the British Journal of Clinical Pharmacology has brought together scientists studying cardiovascular inflammation over a broad range of topics. The aim is to provide an up-todate overview of the current understanding of inflammatory and immune mechanisms in CVD, to summarize the current clinical picture regarding the use of anti-inflammatory drugs in cardiovascular medicine and to discuss future directions towards more specific immune therapies.The themed section is introduced by Welsh et al. (2017). These authors provide an overview of the key therapeutic targets in the treatment of vascular inflammation, placing basic research in a wider clinical perspective. Following the publication of the review article, data from the Phase III Canakinumab Anti-inflammatory Thrombosis Outcomes Study (https://clinicaltrials.gov/ct2/show/NCT01327846) have been published, showing that canakinumab -a monoclonal antibody against IL-1β -in combination with standard therapy reduces recurrent cardiovascular events in patients with a prior myocardial infarction and high levels of circulating C-reactive protein (Ridker et al., 2017). This is the first demonstration in a large, randomized, double-blind, placebo-controlled phase III study that using anti-cytokine-based therapies may be a viable approach for secondary prevention of atherosclerosis-r...

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“…The chronic oral administration of non-selective NSAIDs are linked with many gastrointestinal complications like ulceration, bleeding and perforation (Rafaniello et al), while highly selective COX-2 inhibitors (coxibs) are associated with an increased risk of adverse cardiovascular events (Patrono, 2016). However, in our study, it was not observed any side effects of NSAIDs, which can be reasonable explained by the absence of previous systemic disease in patients, the short-term drug intake and no other age-related factors.…”

Section: Nícoli G A; Conte-neto N; Campos J á D B; Cabrini-mentioning

confidence: 99%

Efficacy of Lumiracoxib Versus Diclofenac Sodium in Pain Control Following Extraction of Impacted Lower Third Molar

Nícoli

Neto

Campos

et al. 2017

Int. J. Odontostomat.

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ABSTRACT:The aim of this paper was to compare the efficacy of two different anti-inflammatory agents, Diclofenac (Deltaflogin ® ) and Lumiracoxib (Prexige ® ) in the control of postoperative pain that results from surgical removal of impacted lower third molars. Twenty adult patients from the Oral and Maxillofacial Surgery Division of the Araraquara Dentistry School, UNESP who presented bilateral impacted lower third molars were included in the study. Removal of the impacted teeth was performed in each side in different operative moments in a split mouth design for the study. The anti-inflammatory drugs evaluated were randomly administered on the first and second surgical procedures. The pain level was recorded using an analogical visual scale at 6, 24, 48 and 72 hours after surgical intervention. Both lumiracoxib 400 mg and diclofenac 100 mg are efficient for acute pain control after surgical removal of impacted lower third molars. However, lumiracoxib offered better pain control.

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Cardiovascular effects of cyclooxygenase‐2 inhibitors: a mechanistic and clinical perspective

Cited by 129 publications

References 72 publications

Inflammatory cell populations in early neuroinflammation in the core and peri-ischemic lesions of rat brain after transient focal cerebral ischemia: A morphometric study

Inflammatory cell populations in early neuroinflammation in the core and peri-ischemic lesions of rat brain after transient focal cerebral ischemia: A morphometric study

Targeting inflammation to reduce cardiovascular disease risk

Efficacy of Lumiracoxib Versus Diclofenac Sodium in Pain Control Following Extraction of Impacted Lower Third Molar

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