Interleukin-6 Receptor Inhibition in Acute St-Segment Elevation Myocardial Infarction: A Randomised Placebo-Controlled Trial

Broch, Kaspar; Anstensrud, Anne Kristine; Woxholt, Sindre; Sharma, Kapil; Tøllefsen, Ingvild Maria; Bendz, Bjørn; Aakhus, Svend; Ueland, Thor; Amundsen, Brage H.; Damås, Jan Kristian; Berg, Erlend Sturle; Bjørkelund, Elisabeth; Bendz, Christina; Hopp, Einar; Kleveland, Ola; Stensæth, Knut Haakon; Opdahl, Anders; Kløw, Nils‐Einar; Seljeflot, Ingebjørg; Andersen, Geir Øystein; Wiseth, Rune; Aukrust, Pål; Gullestad, Lars

doi:10.2139/ssrn.3671415

Cited by 3 publications

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“…Inhibition of IL‐6 and TNF α to improve cardiac healing has yielded variable results in clinical trials. [ 21 ] Thus, IL‐6 and TNF α production in AMI serum exposed macrophages should be interpreted within the full framework of AMI‐induced reprogramming, offering new options for therapeutic design. Slightly surprisingly, efferocytosis turned out to be unaffected by AMI serum exposure.…”

Section: Discussionmentioning

confidence: 99%

Blood Milieu in Acute Myocardial Infarction Reprograms Human Macrophages for Trauma Repair

et al. 2022

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Acute myocardial infarction (AMI) is accompanied by a systemic trauma response that impacts the whole body, including blood. This study addresses whether macrophages, key players in trauma repair, sense and respond to these changes. For this, healthy human monocyte-derived macrophages are exposed to 20% human AMI (n = 50) or control (n = 20) serum and analyzed by transcriptional and multiparameter functional screening followed by network-guided data interpretation and drug repurposing. Results are validated in an independent cohort at functional level (n = 47 AMI, n = 25 control) and in a public dataset. AMI serum exposure results in an overt AMI signature, enriched in debris cleaning, mitosis, and immune pathways. Moreover, gene networks associated with AMI and with poor clinical prognosis in AMI are identified. Network-guided drug screening on the latter unveils prostaglandin E2 (PGE2) signaling as target for clinical intervention in detrimental macrophage imprinting during AMI trauma healing. The results demonstrate pronounced context-induced macrophage reprogramming by the AMI systemic environment, to a degree decisive for patient prognosis. This offers new opportunities for targeted intervention and optimized cardiovascular disease risk management.

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Section: Discussionmentioning

confidence: 99%

Blood Milieu in Acute Myocardial Infarction Reprograms Human Macrophages for Trauma Repair

et al. 2022

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“…Clinical studies have found a variety of inflammatory markers to be closely associated with CMVD (27). Serum C-reactive protein (CRP), as one of the recognized inflammatory markers, is often used to evaluate the level of inflammation in the body, and elevated CRP is also closely associated with impaired vascular endothelial function in CMVD patients (28).…”

Section: Changes In Inflammatory Markers In Cmvd Patientsmentioning

confidence: 99%

“…Levels of IL-6 increase substantially after MI and are associated with poor short-term outcomes. In a randomized, double-blind, placebocontrolled trial, the ASSAIL-MI trial (27), patients with STsegment elevation myocardial infarction (STEMI) who had their inflammatory response attenuated by tocilizumab, a potent agent that blocks IL-6 signaling, experienced a greater than 50% reduction in CRP levels, a lesser extent of microvascular obstruction, and a reduction in the extent of I/R injury. In summary, inflammatory cytokines play an important role in the development of CMVD due to their functions of mediating, regulating, and participating in inflammatory and immune responses.…”

Section: Inflammatory Cytokines Mediate Cmvd Developmentmentioning

confidence: 99%

Inflammation and coronary microvascular disease: relationship, mechanism and treatment

Guo,

Yang,

Song

et al. 2024

Front. Cardiovasc. Med.

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Coronary microvascular disease (CMVD) is common in patients with cardiovascular risk factors and is linked to an elevated risk of adverse cardiovascular events. Although modern medicine has made significant strides in researching CMVD, we still lack a comprehensive understanding of its pathophysiological mechanisms due to its complex and somewhat cryptic etiology. This greatly impedes the clinical diagnosis and treatment of CMVD. The primary pathological mechanisms of CMVD are structural abnormalities and/or dysfunction of coronary microvascular endothelial cells. The development of CMVD may also involve a variety of inflammatory factors through the endothelial cell injury pathway. This paper first reviews the correlation between the inflammatory response and CMVD, then summarizes the possible mechanisms of inflammatory response in CMVD, and finally categorizes the drugs used to treat CMVD based on their effect on the inflammatory response. We hope that this paper draws attention to CMVD and provides novel ideas for potential therapeutic strategies based on the inflammatory response.

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“…Em um outro cenário, agora em pacientes não acometidos por doenças inflamatórias crônicas, estudos recentes evidenciaram que o uso de uma dose única de tocilizumabe pós IAM sem supra-desnível do segmento ST reduziu os níveis séricos de PCRus e troponina T ultra sensível quando comparados ao grupo controle (46) . Já em pacientes com IAM com supra-desnível do segmento ST, a mesma dose única de tocilizumabe antes do tratamento percutâneo aumentou o índice de salvamento miocárdico, mensurado pela ressonância magnética cardíaca, comparado ao grupo placebo (47) .…”

Section: Tratamento Da Doença Aterosclerótica Baseado Na Ação Imunomo...unclassified

O uso da associação de paclitaxel a nanoemulsão lipídica para o tratamento da doença arterial coronariana: estudo randomizado, duplo-cego e controlado por placebo

Marinho

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Interleukin-6 Receptor Inhibition in Acute St-Segment Elevation Myocardial Infarction: A Randomised Placebo-Controlled Trial

Cited by 3 publications

References 0 publications

Blood Milieu in Acute Myocardial Infarction Reprograms Human Macrophages for Trauma Repair

Blood Milieu in Acute Myocardial Infarction Reprograms Human Macrophages for Trauma Repair

Inflammation and coronary microvascular disease: relationship, mechanism and treatment

O uso da associação de paclitaxel a nanoemulsão lipídica para o tratamento da doença arterial coronariana: estudo randomizado, duplo-cego e controlado por placebo

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