Cardiovascular Research最新文献

Cardiac arrest (CA) remains a leading cause of global mortality, largely due to hypoxic-ischaemic brain injury sustained during periods of absent cardiac output. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have demonstrated diagnostic and prognostic potential in neurological and cardiovascular disease. This review assessed the value of miRNAs for predicting six-month neurological outcomes following CA and return of spontaneous circulation (ROSC). Following PRISMA guidelines, PubMed and Cochrane Library searches identified ten clinical studies, comprising four biomarker studies and six post-hoc biomarker analyses from a large randomised controlled trial (RCT). Data on miRNA expression, patient characteristics, predictive accuracy (area under the receiver operating characteristic curve, AUC), and associations with outcome were extracted. Eleven miRNAs were differentially expressed within 72 hours of ROSC; only miR-124-3p (up-regulated at 6 hours) was replicated across studies. Eight studies contributed fifteen AUC values ranging from 0.62 to 0.89. Strong predictors included miR-6511b-5p (6 h, AUC = 0.85), miR-191-5p (48 h, AUC = 0.89), and miR-124 (48 h, AUC = 0.89). Four studies report associations between altered miRNA expression and unfavourable neurological outcomes, whilst one identified miR-122-5p as a positive prognostic biomarker. To conclude, miRNAs demonstrate distinct expression profiles following CA and ROSC, with several showing clinically useful prediction accuracy for six-month neurological outcomes. Larger, unbiased studies using standardised methodologies are required to validate these findings and clarify confounding factors. Despite the current evidence limitations, this data supports further investigation of circulating miRNAs as neuro-prognostic biomarkers after cardiac arrest.

Aims: Atherosclerosis is a major global health challenge, with limited diagnostic and therapeutic options. Macrophages drive disease progression, but their tissue-specific phenotypes and functions remain poorly defined. This study aims to elucidate macrophage-driven mechanisms by characterizing their functional diversity across key metabolic and vascular tissues.

Methods and results: We used single-cell RNA sequencing (scRNA-seq) and translating ribosome affinity purification sequencing (TRAP-seq) to profile macrophage-specific gene programmes in a mouse model of atherosclerosis across the aorta, adipose tissue, and liver. Our data highlight tissue-specific macrophage gene programmes and identify markers that are shared across mouse and human plaques. First, we identified soluble Trem2 as a potential circulating biomarker for differentiating between asymptomatic and symptomatic individuals. Secondly, we leveraged the pronounced expression of Folr2 and Slc7a7 to explore the potential of folate and glutamine as positron emission tomography (PET) tracers for disease burden assessment through in vivo PET imaging. Finally, we show that knockout of Slc7a7 inhibits acetylated low-density lipoprotein uptake and dampens the gene signature linked to lipid-associated macrophages. This suggests that glutamine signalling may play a critical role in foam cell formation, a key event in atherosclerosis.

Conclusion: Our findings provide novel insights into macrophage-specific gene programmes during atherosclerosis progression and identify a set of promising biomarkers that can serve as a resource for future studies. These findings could significantly contribute to improving the diagnosis, monitoring, and treatment of atherosclerosis.

Aims: High dietary salt intake has powerful effects on cerebral blood vessels and has emerged as a risk factor for stroke and cognitive impairment. In mice, a high salt diet (HSD) leads to reduced cerebral blood flow (CBF), tau hyperphosphorylation, and cognitive dysfunction. However, it is still unclear whether the reduced CBF is responsible for the effects of HSD on tau and cognition. Capillary stalling has been linked to cognitive impairment in models of Alzheimer's disease and diabetes. Therefore, we tested the hypothesis that capillary stalling also contributes to CBF reduction, tau accumulation, and cognitive impairment in HSD.

Methods and results: We used in vivo two-photon imaging to assess capillary stalling in C57BL6/J male mice fed a normal diet or HSD. We found that HSD increased stalling of neutrophils in brain capillaries and decreased CBF. Neutrophil depletion using anti-Ly6G antibodies reduced the number of stalled capillaries and restored CBF, measured by red blood cell speed. Despite the improved CBF, chronic neutrophil depletion did not rescue HSD-induced cognitive impairment, assessed by the Barnes maze and nest building behavior. Furthermore, levels of phosphorylated tau in the cortex and hippocampus remained elevated in HSD mice after neutrophil depletion.

Conclusion: These novel findings show that capillary stalling contributes to CBF reduction in HSD, but not to tau phosphorylation and cognitive deficits. Therefore, the hypoperfusion caused by capillary stalling is not the main driver of the tau phosphorylation and cognitive impairment.