The Evolving Role of MicroRNAs in Endothelial Cell Dysfunction in Response to Infection.

The microRNAs are short noncoding RNA molecules responsible for translational repression and silencing of target genes via binding to the mRNA. They are found in all eukaryotic cells and play a critical role in virtually all physiological processes, including within the cardiovascular system where they influence cellular development, differentiation, cardiovascular function, hemostasis, and programmed cell death. Dysregulated microRNA expression is associated with several conditions ranging from cancer and autoimmune disease to infection. Progressively, it has become increasingly clear that microRNAs are important components of the host response to microbes. The cardiovascular system, coupled with cells of the innate immune system, provide the initial interaction and first response to microbial infection, respectively. This review presents the current state of knowledge regarding the role of microRNAs with emphasis on their role in controlling endothelial cell function.

Human endothelial cell-derived exosomal microRNA-99a/b drives a sustained inflammatory response during sepsis by inhibiting mTOR expression.

The pathophysiology of sepsis and its accompanying hyper-inflammatory response are key events that lead to multi-organ failure and death. A growing body of literature now suggests that the vascular endothelium plays a critical role in driving early events of sepsis progression. In this study, we demonstrate how endothelial-derived exosomes contribute to a successive pro-inflammatory phenotype of monocytes. Exosomes isolated from S. aureus infected endothelial cells drive both CD11b and MHCII expression in monocytes and contribute dysregulated cytokine production. Conversely, healthy endothelial exosomes had no major effect. microRNA (miRNA) profiling of exosomes identified miR-99 upregulation which we hypothesised as driving this phenotypic change through mechanistic target of rapamycin (mTOR). Knockdown of mTOR with miR-99a and miR-99b mimetics in S. aureus infected monocytes increased IL-6 and decreased IL-10 production. Interestingly, inhibition of miRNAs with antagomirs has the opposing effect. Collectively, endothelial exosomes are driving a pro-inflammatory phenotype in monocytes through dysregulated expression of miR-99a and miR-99b.

Malnutrition risk of older people across district health board community, hospital and residential care settings in New Zealand.

OBJECTIVE: To determine the prevalence of malnutrition risk in older people across three settings. METHODS: Older people living in the community or newly admitted to hospital or residential care were assessed for malnutrition risk using the validated Mini-Nutritional Assessment - Short Form and dysphagia risk using the Eating Assessment Tool-10. Demographic, physical and health data were collected. RESULTS: Of 167 participants, 23% were malnourished and 35% were at high risk of malnutrition. Those recently admitted to residential care versus a hospital or living in the community had a higher prevalence of malnourishment (47% vs 23% and 2%) (P < 0.001). Risk of dysphagia differed with settings (P < 0.001) with highest risk in residential care. Hospitalised and residential care participants were significantly more likely to have ≥4 comorbidities, take ≥5 medications and have below normal cognition compared to community participants. CONCLUSION: Choice of nutrition intervention is setting dependent.

Coordinated Molecular Cross-Talk between Staphylococcus aureus, Endothelial Cells and Platelets in Bloodstream Infection.

Staphylococcus aureus is an opportunistic pathogen often carried asymptomatically on the human body. Upon entry to the otherwise sterile environment of the cardiovascular system, S. aureus can lead to serious complications resulting in organ failure and death. The success of S. aureus as a pathogen in the bloodstream is due to its ability to express a wide array of cell wall proteins on its surface that recognise host receptors, extracellular matrix proteins and plasma proteins. Endothelial cells and platelets are important cells in the cardiovascular system and are a major target of bloodstream infection. Endothelial cells form the inner lining of a blood vessel and provide an antithrombotic barrier between the vessel wall and blood. Platelets on the other hand travel throughout the cardiovascular system and respond by aggregating around the site of injury and initiating clot formation. Activation of either of these cells leads to functional dysregulation in the cardiovascular system. In this review, we will illustrate how S. aureus establish intimate interactions with both endothelial cells and platelets leading to cardiovascular dysregulation.