Colchicintherapie nach Myokardinfarkt

Klingenberg, Roland; Nitschmann, S.

doi:10.1007/s00108-020-00768-2

Cited by 9 publications

(7 citation statements)

References 5 publications

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“…Those anti-inflammatory therapies did not lower atherogenic lipids but reduce cardiovascular events. 36–38 An ER stress response is also known to activate inflammatory signaling pathways. Specifically, IRE1, one of the ER stress sensors, induces inflammatory responses by interacting TRAF2 to activate NF-κB which is a principal transcriptional regulator of pro-inflammatory pathways.…”

Section: Discussionmentioning

confidence: 99%

A novel VCP modulator, KUS121, attenuates atherosclerosis progression by maintaining intracellular ATP and mitigating ER stress in endothelial cells

Zou,

Baba,

Horie

et al. 2024

Preprint

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Background: Endoplasmic reticulum (ER) stress signaling pathways have pivotal roles in atherosclerosis progression. Recently, we have developed Kyoto University Substance (KUS) 121, which selectively inhibits ATPase activities of valosin-containing protein (VCP) and consequently saves intracellular ATP consumption and mitigates ER stress. Methods and Results: We assessed the efficacy of KUS121 against atherosclerosis by its daily injection into Apoe-/- mice fed with Western Diet (WD) for 8 weeks. Consequently, KUS121 treatment reduced atherosclerosis progression by approximately 40% in atherosclerotic plaques. Interestingly, we found that C/EBP homologous protein (CHOP), an established ER stress marker, was mainly expressed in plaque endothelium. Therefore, we assessed the action of KUS121 in endothelial cells using the human endothelial cell line (EA.hy926 cells). As a result, KUS121 prevented ER stress-induced apoptosis and downregulated the IRE1 (Inositol-requiring enzyme) α-associated inflammatory pathways. Consistent with these in vitro findings, KUS121 treatment also significantly reduced endothelial apoptosis assessed by TUNEL staining and inflammation examined by immunostaining of Nuclear factor kappa B (NF-κB) and Intercellular adhesion molecule (ICAM) 1 at plaque endothelium. We also demonstrated that KUS121 maintained ATP levels in EA.hy926 cells and atherosclerotic plaque lesions using the single-wavelength or the FRET-based fluorescent ATP sensor. Supplementation of intracellular ATP by Methyl pyruvate (MePyr) attenuated ER stress-induced apoptotic and inflammatory pathways in endothelial cells, which could be the main mechanism how KUS121 reduces ER stress. Conclusions: KUS121 can be a new therapeutic option for atherosclerotic diseases by maintaining intracellular ATP levels and attenuating ER stress-induced apoptosis and inflammation in plaque endothelium.

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Section: Discussionmentioning

confidence: 99%

A novel VCP modulator, KUS121, attenuates atherosclerosis progression by maintaining intracellular ATP and mitigating ER stress in endothelial cells

Zou,

Baba,

Horie

et al. 2024

Preprint

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“…Colchicine binds to tubulin, which disrupts microtubule formation and function and exerts thus potent anti‐inflammatory effects. The COLCOT (Colchicine Cardiovascular Outcomes Trial) trial showed successful reduction of the incidence of MI, stroke, by colchicine treatment during the first 3 days compared with placebo in patients who have previously suffered from MI 189 . The LoDoCo1 and 2 (Low‐Dose Colchicine for Secondary Prevention of Cardiovascular Disease) trials demonstrated that 0.5 mg colchicine daily significantly reduced the risk of ischemic cardiovascular events in patients with chronic coronary disease 190,191 .…”

Section: Clinical Trials – Anti‐inflammatory Therapiesmentioning

confidence: 99%

“…The COLCOT (Colchicine Cardiovascular Outcomes Trial) trial showed successful reduction of the incidence of MI, stroke, by colchicine treatment during the first 3 days compared with placebo in patients who have previously suffered from MI. 189 The LoDoCo1 and 2 (Low-Dose Colchicine for Secondary Prevention of Cardiovascular Disease) trials demonstrated that 0.5 mg colchicine daily significantly reduced the risk of ischemic cardiovascular events in patients with chronic coronary disease. 190,191 While colchicine exerts broad antiinflammatory effects, the CANTOS trial tested whether selective inhibition of the pro-inflammatory cytokine Il-1β by the selective IL-1β antibody canakinumab would prevent secondary ischemic events.…”

Section: Anti-inflammatory Therapiesmentioning

confidence: 99%

Macrophage mediators and mechanisms in cardiovascular disease

Schelemei,

Wagner,

Picard

et al. 2024

The FASEB Journal

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Macrophages are major players in myocardial infarction (MI) and atherosclerosis, two major cardiovascular diseases (CVD). Atherosclerosis is caused by the buildup of cholesterol‐rich lipoproteins in blood vessels, causing inflammation, vascular injury, and plaque formation. Plaque rupture or erosion can cause thrombus formation resulting in inadequate blood flow to the heart muscle and MI. Inflammation, particularly driven by macrophages, plays a central role in both atherosclerosis and MI. Recent integrative approaches of single‐cell analysis‐based classifications in both murine and human atherosclerosis as well as experimental MI showed overlap in origin, diversity, and function of macrophages in the aorta and the heart. We here discuss differences and communalities between macrophages in the heart and aorta at steady state and in atherosclerosis or upon MI. We focus on markers, mediators, and functional states of macrophage subpopulations. Recent trials testing anti‐inflammatory agents show a major benefit in reducing the inflammatory burden of CVD patients, but highlight a necessity for a broader understanding of immune cell ontogeny and heterogeneity in CVD. The novel insights into macrophage biology in CVD represent exciting opportunities for the development of novel treatment strategies against CVD.

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“…Several anti-inflammatory medications have been studied, each with a different degree of effectiveness ( Table 1 ) [ 12 , 13 , 19 , 22 , 23 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ].…”

Section: Anti-inflammatory Treatment Strategymentioning

confidence: 99%

Targeting Key Inflammatory Mechanisms Underlying Heart Failure: A Comprehensive Review

Papamichail,

Kourek,

Briasoulis

et al. 2023

IJMS

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Inflammation is a major component of heart failure (HF), causing peripheral vasculopathy and cardiac remodeling. High levels of circulating inflammatory cytokines in HF patients have been well recognized. The hallmark of the inflammatory imbalance is the insufficient production of anti-inflammatory mediators, a condition that leads to dysregulated cytokine activity. The condition progresses because of the pathogenic consequences of the cytokine imbalance, including the impact of endothelial dysfunction and adrenergic responsiveness deterioration, and unfavorable inotropic effects on the myocardium. Hence, to develop possible anti-inflammatory treatment options that will enhance the outcomes of HF patients, it is essential to identify the potential pathophysiological mechanisms of inflammation in HF. Inflammatory mediators, such as cytokines, adhesion molecules, and acute-phase proteins, are elevated during this process, highlighting the complex association between inflammation and HF. Therefore, these inflammatory markers can be used in predicting prognosis of the syndrome. Various immune cells impact on myocardial remodeling and recovery. They lead to stimulation, release of alarmins and risk-related molecule patterns. Targeting key inflammatory mechanisms seems a quite promising therapy strategy in HF. Cytokine modulation is only one of several possible targets in the fight against inflammation, as the potential molecular targets for therapy in HF include immune activation, inflammation, oxidative stress, alterations in mitochondrial bioenergetics, and autophagy.

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Colchicintherapie nach Myokardinfarkt

Cited by 9 publications

References 5 publications

A novel VCP modulator, KUS121, attenuates atherosclerosis progression by maintaining intracellular ATP and mitigating ER stress in endothelial cells

A novel VCP modulator, KUS121, attenuates atherosclerosis progression by maintaining intracellular ATP and mitigating ER stress in endothelial cells

Macrophage mediators and mechanisms in cardiovascular disease

Targeting Key Inflammatory Mechanisms Underlying Heart Failure: A Comprehensive Review

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