European journal of clinical investigation
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Eur. J. Clin. Invest. · Oct 2024
ReviewModulation of mitochondrial permeability transition pores in reperfusion injury: Mechanisms and therapeutic approaches.
Ischemia/reperfusion injury is attracting continuous interest in science for two reasons: because it affects several clinical conditions and because it has been identified, albeit in broad terms, the molecular entity becoming activated by the reperfusion damage paradoxes. Indeed, calcium, oxygen-dependent oxidative stress and pH would activate conformational changes in the mitochondrial cristae embedded F1/FO ATP synthase, allowing the formation of pores in the inner mitochondrial membrane thus increasing its permeability. ⋯ Targeting each of these factors has never contributed to improved clinical outcome of the patients affected by reperfusion damage; now, the focus on the PTP opening could represent the closest target to solve this pathway made by extensive cell death when the tissues become revascularized. In this review, we summarized last knowledge about the structure, the modulation and the therapeutic targeting of the PTP, focusing on ATP synthase and cardiac ischemia/reperfusion.
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Eur. J. Clin. Invest. · Oct 2024
A newly developed, easy-to-use prehospital drug-derived score compared with three conventional scores: A prospective multicenter study.
The use of medications by emergency medical services (EMS) is increasing. Conventional scores are time-consuming and therefore difficult to use in an emergency setting. For early decision-making, an easy-to-use score based on the medications administered by the EMS may have prognostic value. The primary objective of this study was to develop the prehospital drug-derived score (PDDS) for 2-day mortality. ⋯ The newly developed easy-to-use prehospital drug-derived PDDS score has an excellent predictive value of early mortality. The PDDS score was comparable to the conventional risk scores and therefore might serve as an alternative score in the prehospital emergency setting.
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Eur. J. Clin. Invest. · Oct 2024
ACKR3 agonism induces heterodimerization with chemokine receptor CXCR4 and attenuates platelet function.
Platelet receptors ACKR3 and CXCR4 play a crucial role in a variety of cardiovascular diseases. Like most chemokine receptors, CXCR4 is a G protein coupled receptor that induces platelet activation. In contrast, the atypical chemokine receptor 3 (ACKR3) lacks the ability to activate heterotrimeric G proteins and its activation leads to platelet inhibition and attenuates thrombus formation. In nucleated cells, heterodimerization of ACKR3 with CXCR4 regulates CXCL12-dependent signalling. The aim of our study was to investigate the formation of ACKR3/CXCR4 heterodimers in platelets and the subsequent consequences for platelet function. ⋯ Our results reveal that the formation of platelet ACKR3/CXCR4 heterodimers is dependent on ACKR3 rather than CXCR4. Furthermore, ACKR3 agonism induced heterodimerization is associated with mitigating CXCL12/CXCR4-dependent platelet activation possibly by modulating CXCR4-dependent G protein signalling. Our results indicate possible ACKR3 agonist functions and reinforce the potential therapeutic applications of ACKR3 agonists.
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Eur. J. Clin. Invest. · Oct 2024
ReviewHypercholesterolemia and inflammation-Cooperative cardiovascular risk factors.
Maintaining low concentrations of plasma low-density lipoprotein cholesterol (LDLc) over time decreases the number of LDL particles trapped within the artery wall, slows the progression of atherosclerosis and delays the age at which mature atherosclerotic plaques develop. This substantially reduces the lifetime risk of atherosclerotic cardiovascular disease (ASCVD) events. In this context, plaque development and vulnerability result not only from lipid accumulation but also from inflammation. ⋯ Identifying clinical biomarkers of inflammation (e.g. interleukin-6) and possible targets for therapy holds promise for monitoring and reducing the ASCVD burden in suitable patients.
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Eur. J. Clin. Invest. · Oct 2024
Phenotypes of Polish primary care patients using hierarchical clustering: Exploring the risk of mortality in the LIPIDOGEN2015 study cohort.
Comorbidities in primary care do not occur in isolation but tend to cluster together causing various clinically complex phenotypes. This study aimed to distinguish phenotype clusters and identify the risks of all-cause mortality in primary care. ⋯ Overweight/obesity older patients with more comorbidities had the highest risk of long-term all-cause mortality, and in the young group population overweight/obesity insignificantly increased the risk in the long-term follow-up, providing a basis for stratified phenotypic risk management.