Abstract
Background/Introduction
The pro-thrombotic immature or reticulated platelets (RPs) are known to be elevated in high risk patients and in different pathological settings. Several studies have ...shown that RPs correlate with an insufficient antiplatelet response to antiplatelet agents. In addition, RPs are emerging novel biomarkers for the prediction of adverse cardiovascular events in cardiovascular disease.
Purpose
The current study, using the totality of existing evidence, evaluated the prognostic role of RPs in patients with coronary artery disease.
Methods
We performed a systematic review and meta-analysis including trials of acute and chronic coronary syndrome reporting clinical outcomes according to RPs levels in the peripheral blood. Patients with elevated RPs were defined as RPshigh according to the single study definitions and compared to patients without elevated RPs (RPslow). Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints were cardiovascular death, myocardial infarction, ischemic stroke, urgent coronary revascularization and any bleeding. Prospero Registration number: CRD42022381282.
Results
A total of 7 studies, including 2213 patients, were included. The risk for MACCE was significantly higher in RPshigh compared to RPslow patients (OR 2.67 1.87; 3.81, I2=43.8%, Figure 1). RPshigh were significantly associated with cardiovascular death (OR 2.09 1.36; 3.22, I2=40.4%). No significant associations for RPshigh were detected with the other singular components of MACCE: myocardial infarction (OR 1.73 0.89; 3.38 I2=60.5%) and stroke (OR 1.72 0.59; 4.96 I2=21%). Urgent revascularization was not significantly associated with elevated RPs (OR 2.09 0.90; 4.86 I2=55.5%). The risk of bleeding did not significantly differ between groups(OR 0.58 0.15; 2.22 I2=86.1%).
Conclusion
Elevated RPs are significantly associated with increased risk of cardiovascular events and cardiovascular death in patients with coronary artery disease and should be considered a useful prognostic biomarker in this setting.Figure 1
Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Else Kröner Fresenius Stiftung Background Reticulated platelets (RPs), ...characterized by youth, hyper-reactivity, and RNA abundance, signify pro-thrombotic potential and serve as predictors for inadequate antiplatelet therapy response post-myocardial infarction. Their pivotal role in chronic coronary syndrome (CCS) and high on-treatment platelet reactivity highlights their significance as promising biomarkers for adverse cardiovascular events in diverse pathological settings. Purpose We aimed to compare for the first time the transcriptomic profiles of RPs and MPs in CCS patients. Methods Using fluorescent activated cell sorting (FACS), RPs and MPs were isolated based on RNA content from peripheral blood of 19 CCS patients. RNA assessment involved the Tapestation 4200 platform (Agilent), and totalRNA libraries were sequenced on a NextSeq 500 Illumina platform. RNA sequencing analysis, with a cut-off of p <0.005 and a log2fc >1, and alternative splicing event detection using MAJIQ, were performed. Circular RNA (circRNA) analysis employed CIRCexplorer. Results Total RNA-sequencing identified 1589 differentially expressed genes, with 1100 transcripts upregulated in RPs and 489 enriched in MPs (Figure 1 A, B and D). Notably, collagen receptor GP6 (log2FC 1.12, p=6.89x10-41), thrombin receptor PAR4 (F2RL3, log2FC 1.1, p=3.54*10-21) and Von Willebrand Factor (log2FC 1.2, p=1.26*10-38) transcripts were significantly enriched in RPs. Gene Ontology identified a higher enrichment of relevant biological categories in RPs compared to MPs, such as "platelet activation", "platelet degranulation" and "blood coagulation" (Figure 1C). These findings are consistent with our previously established discovery and support the hypothesis that RPs in cardiovascular disease are hyper-reactive and pro-thrombotic due to their different RNA content compared to other platelets. Several splicing events were detected as differentially regulated: there is an upregulation of an alternative splicing on the collagen receptor transcript GP6 in RPs (Figure 1E); by the transcript of the G-protein GNAQ, one alternative splicing event was found upregulated in RPs, whilst two others were upregulated in MPs. Moreover, we found an enrichment of the total level of circular RNAs in MPs as compared to RPs (Figure 1F). Several previously undescribed circular RNAs were discovered to be enriched in RPs, as shown in Figure 1F. Conclusion This groundbreaking transcriptomic profiling of RPs and MPs in CCS patients elucidates the biological basis for RPs' hyperreactivity, emphasizing the differential enrichment of platelet activation transcripts. The pronounced upregulation of prothrombotic signaling in RPs provides insight into their hyperactivity and correlation with cardiovascular events. These findings illuminate a novel therapeutic niche in CCS patients, although further investigations are essential to comprehend the detrimental role of RPs in coronary artery disease.
Antimicrobial peptides are effector molecules of the innate immune system and contribute to host defense and regulation of inflammation. The human cathelicidin antimicrobial peptide LL-37/hCAP-18 is ...expressed in leukocytes and epithelial cells and secreted into wound and airway surface fluid. Here we show that LL-37 induces angiogenesis mediated by formyl peptide receptor–like 1 expressed on endothelial cells. Application of LL-37 resulted in neovascularization in the chorioallantoic membrane assay and in a rabbit model of hind-limb ischemia. The peptide directly activates endothelial cells, resulting in increased proliferation and formation of vessel-like structures in cultivated endothelial cells. Decreased vascularization during wound repair in mice deficient for CRAMP, the murine homologue of LL-37/hCAP-18, shows that cathelicidin-mediated angiogenesis is important for cutaneous wound neovascularization in vivo. Taken together, these findings demonstrate that LL-37/hCAP-18 is a multifunctional antimicrobial peptide with a central role in innate immunity by linking host defense and inflammation with angiogenesis and arteriogenesis.
This article presents the case of a 22-year-old male patient with cardiomyopathy associated with a long history of methamphetamine abuse. Echocardiography revealed a dilated cardiomyopathy with ...highly reduced systolic pump function and severe mitral valve regurgitation. Inotropic treatment and MitraClip® (Abbott Vascular, Santa Clara, CA, USA) implantation resulted in enhancement of hemodynamics. The rising prevalence of methamphetamine abuse should give reason to raise awareness for the diagnostic work-up and patient history particularly in cases of unexplained cardiomyopathy in young patients.
Zusammenfassung
Herzinsuffizienz (HI) geht mit hoher Mortalität und häufigen Hospitalisierungen einher; Prävalenz und Krankheitskosten steigen kontinuierlich. Zur Optimierung der Versorgung bei HI ...müssen strukturierte sektorenübergreifende Kooperationen etabliert und die Behandlungsqualität und -kontinuität sichergestellt werden. Kooperationspartner sind Hausärzte, kardiologische Praxen, Abteilungen regionaler Krankenhäuser und überregionale Zentren mit umfassendem, auch kardiochirurgischem Behandlungsspektrum. Die Deutsche Gesellschaft für Kardiologie – Herz- und Kreislaufforschung (DGK) und die Deutsche Gesellschaft für Thorax-, Herz- und Gefäßchirurgie (DGTHG) empfehlen die Einrichtung von
Herzinsuffizienz-Netzwerken (HF-NETs)
, die modular auf den verschiedenen Versorgungsebenen in Herzinsuffizienz-Einheiten („Heart Failure Units“, HFUs) organisiert sind und damit überprüfbare Qualitätsmerkmale für die sektorenübergreifende Versorgung von HI-Patienten aufweisen. Das dazu vorgelegte Positionspapier wurde von der Kommission für Klinische Kardiologie mit Vertretern von DGK, DGTHG, sowie des Bundes Niedergelassener Kardiologen (BNK) und der Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte (ALKK) erarbeitet. Es formuliert die Voraussetzungen, die von den modularen HFUs im HF-NET für eine Zertifizierung erfüllt sein sollen.
Die kathetergestützte Rekonstruktion der Klappen stellt eine mittlerweile relevante Alternative zur rein medikamentösen bzw. chirurgischen Behandlung dar.
The interaction of the heat shock protein 90 (Hsp90) with the endothelial NO synthase (eNOS) has been shown to account for a sustained production of NO in vitro. Here, we examined whether ...overexpression of Hsp90 in a pig model of cardiac infarct could preserve the myocardium from the deleterious effects of ischemia-reperfusion.
Percutaneous liposome-based gene transfer was performed by retroinfusion of the anterior interventricular vein before left anterior descending occlusion and reperfusion. We found that recombinant Hsp90 expression in the ischemic region of the heart led to a 33% reduction in infarct size and prevented the increase in postischemic left ventricular end diastolic pressure observed in mock-transfected animals. Regional myocardial function, assessed by subendocardial segment shortening in the infarct region, was increased in Hsp90-transfected animals at baseline and after pacing. All these effects were completely abrogated by administration of the NOS inhibitor N(G)-nitro-L-arginine methyl ester. We further documented in vivo and in cultured endothelial cells that the cardioprotective effects of Hsp90 were associated to its capacity to act as an adaptor for both the kinase Akt and the phosphatase calcineurin, thereby promoting eNOS serine 1177 phosphorylation and threonine 495 dephosphorylation, respectively.
Hsp90 is a promising target to enhance NO formation in vivo, which may efficiently reduce myocardial reperfusion injury.
In der Legende der Abb. 1 des Originalbeitrags wurde die Abkürzung „TMVR“ falsch aufgelöst. Richtig muss es heißen: „TMVR kathetergestützte Mitralklappenrekonstruktion“. Nachfolgend finden Sie die ...Abbildung mit der korrekten Legende. Wir bitten, diesen Fehler zu entschuldigen und die korrigierte …
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