Mammalian Target of Rapamycin Inhibition in Patients With ST-Segment Elevation Myocardial Infarction

Stähli, Barbara E.; Klingenberg, Roland; Heg, Dik; Branca, Mattia; Manka, Robert; Kapos, Ioannis; Müggler, Oliver; Denegri, Andrea; Kesterke, Rahel; Berger, Florence; Stehli, Julia; Candreva, Alessandro; Eckardstein, Arnold von; Carballo, David; Hamm, Christian W.; Landmesser, Ulf; Mach, François; Moccetti, Tiziano; Jung, Christian; Kelm, Malte; Münzel, Thomas; Pedrazzini, Giovanni; Räber, Lorenz; Windecker, Stephan; Templin, Christian; Matter, Christian M.; Lüscher, Thomas F.; Ruschitzka, Frank

doi:10.1016/j.jacc.2022.08.747

Cited by 13 publications

(6 citation statements)

References 40 publications

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“…The CANTOS study demonstrated that anti-inflammatory therapy with canakinumab—a monoclonal antibody targeting interleukin-1β—at 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo (HR 0.83; 95% CI, 0.73 to 0.95; p = 0.005), with a higher incidence of fatal infection [ 120 ]. Other anti-inflammatory agents, such as methotrexate and everolimus, are currently not recommended for secondary prevention due to uncertain efficacy [ 121 , 122 ].…”

Section: Therapeutic Implication Of Intracoronary Imagingmentioning

confidence: 99%

Intracoronary Imaging of Coronary Atherosclerotic Plaque: From Assessment of Pathophysiological Mechanisms to Therapeutic Implication

Gurgoglione

Denegri

Russo

et al. 2023

IJMS

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Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality worldwide. Several cardiovascular risk factors are implicated in atherosclerotic plaque promotion and progression and are responsible for the clinical manifestations of coronary artery disease (CAD), ranging from chronic to acute coronary syndromes and sudden coronary death. The advent of intravascular imaging (IVI), including intravascular ultrasound, optical coherence tomography and near-infrared diffuse reflectance spectroscopy has significantly improved the comprehension of CAD pathophysiology and has strengthened the prognostic relevance of coronary plaque morphology assessment. Indeed, several atherosclerotic plaque phenotype and mechanisms of plaque destabilization have been recognized with different natural history and prognosis. Finally, IVI demonstrated benefits of secondary prevention therapies, such as lipid-lowering and anti-inflammatory agents. The purpose of this review is to shed light on the principles and properties of available IVI modalities along with their prognostic significance.

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Section: Therapeutic Implication Of Intracoronary Imagingmentioning

confidence: 99%

Intracoronary Imaging of Coronary Atherosclerotic Plaque: From Assessment of Pathophysiological Mechanisms to Therapeutic Implication

Gurgoglione

Denegri

Russo

et al. 2023

IJMS

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“…In contrast, the recently published Controlled Level EVERolimus in Acute Coronary Syndromes (CLEVER-ACS) trial enrolled patients within a time window of up to 5 days after PCI. 93 The trial showed negative results regarding its primary CMR-based endpoint. Firstly, the chosen target (murine target of rapamycin) is broad and relatively unspecific as to targeting ‘The Bad’.…”

Section: Most Wanted: ‘The Ugly’ and ‘The Bad’—how Can They Be Captured?mentioning

confidence: 99%

Inflammation in acute myocardial infarction: the good, the bad and the ugly

Matter,

Paneni,

Libby

et al. 2023

European Heart Journal

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Convergent experimental and clinical evidence have established the pathophysiological importance of pro-inflammatory pathways in coronary artery disease. Notably, the interest in treating inflammation in patients suffering acute myocardial infarction (AMI) is now expanding from its chronic aspects to the acute setting. Few large outcome trials have proven the benefits of anti-inflammatory therapies on cardiovascular outcomes by targeting the residual inflammatory risk (RIR), i.e. the smouldering ember of low-grade inflammation persisting in the late phase after AMI. However, these studies have also taught us about potential risks of anti-inflammatory therapy after AMI, particularly related to impaired host defence. Recently, numerous smaller-scale trials have addressed the concept of targeting a deleterious flare of excessive inflammation in the early phase after AMI. Targeting different pathways and implementing various treatment regimens, those trials have met with varied degrees of success. Promising results have come from those studies intervening early on the interleukin-1 and -6 pathways. Taking lessons from such past research may inform an optimized approach to target post-AMI inflammation, tailored to spare ‘The Good’ (repair and defence) while treating ‘The Bad’ (smouldering RIR) and capturing ‘The Ugly’ (flaming early burst of excess inflammation in the acute phase). Key constituents of such a strategy may read as follows: select patients with large pro-inflammatory burden (i.e. large AMI); initiate treatment early (e.g. ≤12 h post-AMI); implement a precisely targeted anti-inflammatory agent; follow through with a tapering treatment regimen. This approach warrants testing in rigorous clinical trials.

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“…The use of autophagy as a therapeutic modality has gained widespread support in recent years. Studies have found that autophagy regulators, including rapamycin [ 109 ], sulfaphenazole [ 110 ], UTP [ 111 ] and ranolazine [ 25 ] can reduce the myocardial infarct area, improve cardiac function and protect against myocardial ischemia. Rapamycin has been shown to reduce cardiomyocyte apoptosis and promote cardiomyocyte autophagy by modulating the crosstalk of mTOR and endoplasmic reticulum stress pathway components in the chronic heart failure context [ 112 ].…”

Section: Reviewmentioning

confidence: 99%

Myocardial injury: where inflammation and autophagy meet

Liu

Chen

et al. 2023

Burns &Amp; Trauma

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Autophagy is a highly conserved bulk degradation mechanism that degrades damaged organelles, aged proteins and intracellular contents to maintain the homeostasis of the intracellular microenvironment. Activation of autophagy can be observed during myocardial injury, during which inflammatory responses are strongly triggered. Autophagy can inhibit the inflammatory response and regulate the inflammatory microenvironment by removing invading pathogens and damaged mitochondria. In addition, autophagy may enhance the clearance of apoptotic and necrotic cells to promote the repair of damaged tissue. In this paper, we briefly review the role of autophagy in different cell types in the inflammatory microenvironment of myocardial injury and discuss the molecular mechanism of autophagy in regulating the inflammatory response in a series of myocardial injury conditions, including myocardial ischemia, ischemia/reperfusion injury and sepsis cardiomyopathy.

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Mammalian Target of Rapamycin Inhibition in Patients With ST-Segment Elevation Myocardial Infarction

Cited by 13 publications

References 40 publications

Intracoronary Imaging of Coronary Atherosclerotic Plaque: From Assessment of Pathophysiological Mechanisms to Therapeutic Implication

Intracoronary Imaging of Coronary Atherosclerotic Plaque: From Assessment of Pathophysiological Mechanisms to Therapeutic Implication

Inflammation in acute myocardial infarction: the good, the bad and the ugly

Myocardial injury: where inflammation and autophagy meet

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