Leicester Cardiovascular Biomedical Research Unit

Leicester, United Kingdom

Leicester Cardiovascular Biomedical Research Unit

Leicester, United Kingdom
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Romaine S.P.R.,University of Leicester | Romaine S.P.R.,Leicester Cardiovascular Biomedical Research Unit | Charchar F.J.,Federation University Australia | Samani N.J.,University of Leicester | And 2 more authors.
Current Opinion in Pharmacology | Year: 2016

Hypertension is a leading cause of cardiovascular morbidity and mortality worldwide, yet the molecular mechanisms underpinning the development of high blood pressure remain incompletely understood. MicroRNAs are small, non-coding RNA molecules approximately 22 nucleotides in length that act as post-transcriptional regulators of gene expression. We highlight, through a review of recent literature, that studies on circulating microRNAs have provided novel insights into blood pressure regulation. They have also complemented tissue-based and animal-based experiments in shedding new light on our understanding of established pathways in hypertension, such as the renin-angiotensin system. Despite a number of challenges, we believe microRNAs herald particular potential in becoming effective biomarkers of target-organ damage in hypertension. © 2016 Elsevier Ltd. All rights reserved.


Chung E.M.L.,University of Leicester | Chung E.M.L.,Leicester Cardiovascular Biomedical Research Unit | Banahan C.,University of Leicester | Patel N.,University of Leicester | And 9 more authors.
PLoS ONE | Year: 2015

Background Thousands of air bubbles enter the cerebral circulation during cardiac surgery, but whether high numbers of bubbles explain post-operative cognitive decline is currently controversial. This study estimates the size distribution of air bubbles and volume of air entering the cerebral arteries intra-operatively based on analysis of transcranial Doppler ultrasound data. Methods Transcranial Doppler ultrasound recordings from ten patients undergoing heart surgery were analysed for the presence of embolic signals. The backscattered intensity of each embolic signal was modelled based on ultrasound scattering theory to provide an estimate of bubble diameter. The impact of showers of bubbles on cerebral blood-flow was then investigated using patient-specific Monte-Carlo simulations to model the accumulation and clearance of bubbles within a model vasculature. Results Analysis of Doppler ultrasound recordings revealed a minimum of 371 and maximum of 6476 bubbles entering the middle cerebral artery territories during surgery. This was estimated to correspond to a total volume of air ranging between 0.003 and 0.12 mL. Based on analysis of a total of 18667 embolic signals, the median diameter of bubbles entering the cerebral arteries was 33 μm (IQR: 18 to 69 μm). Although bubble diameters ranged from ∼5 μm to 3.5 mm, the majority (85%) were less than 100 μm. Numerous small bubbles detected during cardiopulmonary bypass were estimated by Monte-Carlo simulation to be benign. However, during weaning from bypass, showers containing large macro-bubbles were observed, which were estimated to transiently affect up to 2.2% of arterioles. Conclusions Detailed analysis of Doppler ultrasound data can be used to provide an estimate of bubble diameter, total volume of air, and the likely impact of embolic showers on cerebral blood flow. Although bubbles are alarmingly numerous during surgery, our simulations suggest that the majority of bubbles are too small to be harmful. © 2015 Chung et al.


PubMed | University of Leicester, Open University Milton Keynes and Leicester Cardiovascular Biomedical Research Unit
Type: Journal Article | Journal: PloS one | Year: 2015

Thousands of air bubbles enter the cerebral circulation during cardiac surgery, but whether high numbers of bubbles explain post-operative cognitive decline is currently controversial. This study estimates the size distribution of air bubbles and volume of air entering the cerebral arteries intra-operatively based on analysis of transcranial Doppler ultrasound data.Transcranial Doppler ultrasound recordings from ten patients undergoing heart surgery were analysed for the presence of embolic signals. The backscattered intensity of each embolic signal was modelled based on ultrasound scattering theory to provide an estimate of bubble diameter. The impact of showers of bubbles on cerebral blood-flow was then investigated using patient-specific Monte-Carlo simulations to model the accumulation and clearance of bubbles within a model vasculature.Analysis of Doppler ultrasound recordings revealed a minimum of 371 and maximum of 6476 bubbles entering the middle cerebral artery territories during surgery. This was estimated to correspond to a total volume of air ranging between 0.003 and 0.12 mL. Based on analysis of a total of 18667 embolic signals, the median diameter of bubbles entering the cerebral arteries was 33 m (IQR: 18 to 69 m). Although bubble diameters ranged from ~5 m to 3.5 mm, the majority (85%) were less than 100 m. Numerous small bubbles detected during cardiopulmonary bypass were estimated by Monte-Carlo simulation to be benign. However, during weaning from bypass, showers containing large macro-bubbles were observed, which were estimated to transiently affect up to 2.2% of arterioles.Detailed analysis of Doppler ultrasound data can be used to provide an estimate of bubble diameter, total volume of air, and the likely impact of embolic showers on cerebral blood flow. Although bubbles are alarmingly numerous during surgery, our simulations suggest that the majority of bubbles are too small to be harmful.


Stather P.W.,University of Leicester | Wild J.B.,University of Leicester | Sylvius N.,University of Leicester | Choke E.,Leicester Cardiovascular Biomedical Research Unit | And 2 more authors.
Artery Research | Year: 2013

Objectives: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at a post-transcriptional level. Through binding to mRNA sequences, miRNAs have a wide variety of functions, and are key regulators in vascular disease. Although there are only 2 papers looking directly at the association between miRNA and abdominal aortic aneurysms (AAA), several studies have looked at miRNAs implicated in vascular smooth muscle cell (VSMC) proliferation, extracellular matrix (ECM) remodelling, and the known genes and genetic loci associated with AAA. This review aims to determine potential miRNAs associated with the pathways involved in abdominal aortic aneurysm (AAA) pathophysiology, to guide future focused research. Methods and results: A systematic review of the published literature was performed, searching for articles detailing miRNA associations with AAA or processes associated with aneurysm formation. Eighteen miRNAs were identified to be associated with aneurysm formation, ten miRNAs were associated with VSMC physiology, and nine miRNAs were involved in regulation of the ECM. Seven miRNAs were replicated in more than 1 study (miR-19b, miR-21, miR-26a, miR-29b, miR-146a, miR-221, miR-222). Conclusions: The association between miRNAs associated with known AAA genes, and those involved in VSMC/ECM pathophysiology highlight promising areas for further significantly powered human studies, which with miRNA level modulation, present a novel opportunity to determine pathways for AAA formation. © 2012 Association for Research into Arterial Structure and Physiology.

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