The interleukin-1β modulator gevokizumab reduces neointimal proliferation and improves reendothelialization in a rat carotid denudation model

Roubille, François; Busseuil, David; Shi, Yanfen; Nachar, Walid; Mihalache-Avram, Téodora; Mecteau, Mélanie; Gillis, Marc‐Antoine; Brand, Geneviève; Théberge-Julien, Gabriel; Brodeur, Mathieu R.; Kernaleguen, Anne-Elen; Gombos, Mélania; Rhéaume, Éric; Tardif, Jean‐Claude

doi:10.1016/j.atherosclerosis.2014.07.012

Cited by 15 publications

(9 citation statements)

References 24 publications

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“…In rats, a single administration of gevokizumab 1 mg/kg improves endothelial regrowth and reduces neointima formation in rats following carotid denudation, at least in part through its beneficial effects on endothelial cells [123]. Furthermore, gevokizumab has been considered as a potential drug to protect b-cell against IL-1-induced inflammation in patients with type 1 diabetes [124].…”

Section: Gevokinumabmentioning

confidence: 98%

Anti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease

Esser

Paquot

Scheen

2014

Expert Opinion on Investigational Drugs

217

150

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The available data supports the concept that targeting inflammation improves insulin sensitivity and β-cell function; it also ameliorates glucose control in insulin-resistant patients with inflammatory rheumatoid diseases as well in patients with metabolic syndrome or T2DM. Although promising, the observed metabolic effects remain rather modest in most clinical trials. The potential use of combined anti-inflammatory agents targeting both insulin resistance and insulin secretion appears appealing but remains unexplored. Large-scale prospective clinical trials are underway to investigate the safety and efficacy of different anti-inflammatory drugs. Further evidence is needed to support the concept that targeting inflammation pathways may represent a valuable option to tackle the cardiometabolic complications of obesity.

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Section: Gevokinumabmentioning

confidence: 98%

Anti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease

Esser

Paquot

Scheen

2014

Expert Opinion on Investigational Drugs

217

150

View full text Add to dashboard Cite

show abstract

“…Several developments have highlighted this effort more excitingly than the advent of percutaneous coronary intervention (PCI), whereby a metallic scaffold device (MESs) alone or sometimes loaded with drug eluting stents (DESs) are deployed to relieve obstructive atherosclerotic lesions, but the effectiveness of PCI is impeded by NI formation, resulting in re-narrowing of the stented artery, a process known as in-stent restenosis (ISR). Although DESs reduce the frequency of ISR, the associated impaired Re-endothelialization (ReEndo) and the resultant risk of stent thrombosis due to the drug and/or the polymer in these devices remain formidable obstacles for complete therapy [ 1 – 4 ].…”

Section: Introductionmentioning

confidence: 99%

IL-10 Accelerates Re-Endothelialization and Inhibits Post-Injury Intimal Hyperplasia following Carotid Artery Denudation

et al. 2016

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The role of inflammation on atherosclerosis and restenosis is well established. Restenosis is thought to be a complex response to injury, which includes early thrombus formation, acute inflammation and neo-intimal growth. Inflammatory cells are likely contributors in the host response to vascular injury, via cytokines and chemokines secretion, including TNF-alpha (TNF). We have previously shown that IL-10 inhibits TNF and other inflammatory mediators produced in response to cardiovascular injuries. The specific effect of IL-10 on endothelial cell (ECs) biology is not well elucidated. Here we report that in a mouse model of carotid denudation, IL-10 knock-out mice (IL-10KO) displayed significantly delayed Re-endothelialization and enhanced neo-intimal growth compared to their WT counterparts. Exogenous recombinant IL-10 treatment dramatically blunted the neo-intimal thickening while significantly accelerating the recovery of the injured endothelium in WT mice. In vitro, IL-10 inhibited negative effects of TNF on ECs proliferation, ECs cell cycle, ECs-monocyte adhesion and ECs apoptosis. Furthermore, IL-10 treatment attenuated TNF-induced smooth muscle cells proliferation. Our data suggest that IL-10 differentially regulate endothelial and vascular smooth cells proliferation and function and thus inhibits neo-intimal hyperplasia. Thus, these results may provide insights necessary to develop new therapeutic strategies to limit vascular restenosis during percutaneous coronary intervention (PCI) in the clinics.

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“…These future studies will provide us with a broad understanding of IL-1β roles in atherosclerotic vascular calcification, and will define the value of IL-1β as a potential therapeutic target in the treatment of patients with cardiovascular diseases. [156,157] Monoclonal anti-IL-1β antibody In vitro and in vivo Gevokizumab [158] IL-1β modulator In vitro and in vivo Anakinra [152][153][154][155] Recombinant IL-1 receptor antagonist (IL-1Ra) Clinical trial Canakinumab [20,144] Monoclonal…”

Section: Discussionmentioning

confidence: 99%

IL-1β in atherosclerotic vascular calcification: From bench to bedside

Jia-ling¹,

Zhao²,

Zhang³

et al. 2021

Int. J. Biol. Sci.

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Atherosclerotic vascular calcification contributes to increased risk of death in patients with cardiovascular diseases. Assessing the type and severity of inflammation is crucial in the treatment of numerous cardiovascular conditions. IL-1β, a potent proinflammatory cytokine, plays diverse roles in the pathogenesis of atherosclerotic vascular calcification. Several large-scale, population cohort trials have shown that the incidence of cardiovascular events is clinically reduced by the administration of anti-IL-1β therapy. Anti-IL-1β therapy might reduce the incidence of cardiovascular events by affecting atherosclerotic vascular calcification, but the mechanism underlying this effect remains unclear. In this review, we summarize current knowledge on the role of IL-1β in atherosclerotic vascular calcification, and describe the latest results reported in clinical trials evaluating anti-IL-1β therapies for the treatment of cardiovascular diseases. This review will aid in improving current understanding of the pathophysiological roles of IL-1β and mechanisms underlying its activity.

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The interleukin-1β modulator gevokizumab reduces neointimal proliferation and improves reendothelialization in a rat carotid denudation model

Cited by 15 publications

References 24 publications

Anti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease

Anti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease

IL-10 Accelerates Re-Endothelialization and Inhibits Post-Injury Intimal Hyperplasia following Carotid Artery Denudation

IL-1β in atherosclerotic vascular calcification: From bench to bedside

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