Background:
Understanding the processes behind carotid plaque instability is necessary to develop methods for identification of patients and lesions with stroke risk. Here, we investigated molecular signatures in human plaques stratified by echogenicity as assessed by duplex ultrasound.
Methods:
Lesion echogenicity was correlated to microarray gene expression profiles from carotid endarterectomies (n=96). The findings were extended into studies of human and mouse atherosclerotic lesions in situ, followed by functional investigations in vitro in human carotid smooth muscle cells (SMCs).
Results:
Pathway analyses highlighted muscle differentiation, iron homeostasis, calcification, matrix organization, cell survival balance, and
BCLAF1
(BCL2 [B-cell lymphoma 2]-associated transcription factor 1) as the most significant signatures.
BCLAF1
was downregulated in echolucent plaques, positively correlated to proliferation and negatively to apoptosis. By immunohistochemistry, BCLAF1 was found in normal medial SMCs. It was repressed early during atherogenesis but reappeared in CD68+ cells in advanced plaques and interacted with BCL2 by proximity ligation assay. In cultured SMCs, BCLAF1 was induced by differentiation factors and mitogens and suppressed by macrophage-conditioned medium. BCLAF1 silencing led to downregulation of BCL2 and SMC markers, reduced proliferation, and increased apoptosis. Transdifferentiation of SMCs by oxLDL was accompanied by upregulation of BCLAF1, CD36, and CD68, while oxLDL exposure with BCLAF1 silencing preserved MYH (myosin heavy chain) 11 expression and prevented transdifferentiation.
BCLAF1
was associated with expression of cell differentiation, contractility, viability, and inflammatory genes, as well as the scavenger receptors
CD36
and
CD68
. BCLAF1 expression in CD68+/BCL2+ cells of SMC origin was verified in plaques from MYH11 lineage-tracing atherosclerotic mice. Moreover,
BCLAF1
downregulation associated with vulnerability parameters and cardiovascular risk in patients with carotid atherosclerosis.
Conclusions:
Plaque echogenicity correlated with enrichment of distinct molecular pathways and identified
BCLAF1
, previously not described in atherosclerosis, as the most significant gene. Functionally, BCLAF1 seems necessary for survival and transdifferentiation of SMCs into a macrophage-like phenotype. The role of BCLAF1 in plaque vulnerability should be further evaluated.
Background
The Doppler-derived renal resistive index (RRI) is emerging as a promising bedside tool for assessing renal perfusion and risk of developing acute kidney injury in critically ill patients. It is not known what level of ultrasonography competence is needed to obtain reliable RRI values.
Objective
The aim of this study was to evaluate the feasibility of RRI measurements by an intermediate and novice sonographer in a volunteer population.
Methods
After a focused teaching session, an intermediate (resident), novice (medical student) and expert sonographer performed RRI measurements in 23 volunteers consecutively and blinded to the results of one another. Intraclass correlation coefficients and Bland–Altman plots were used to evaluate interobserver reliability, bias and precision.
Results
Both non-experts were able to obtain RRI values in all volunteers. Median RRI in the population measured by the expert was 0.58 (interquartile range 0.52–0.62). The intraclass correlation coefficient was 0.96 (95% confidence interval 0.90–0.98) for the intermediate and expert, and 0.85 (95% confidence interval 0.69–0.94) for the novice and expert. In relation to the measurements of the expert, both non-experts showed negligible bias (mean difference 0.002 [95% confidence interval − 0.005 to 0.009, p = 0.597] between intermediate and expert, mean difference 0.002 [95% confidence interval − 0.011 to 0.015, p = 0.752] between novice and expert) and clinically acceptable precision (95% limits of agreement − 0.031 to 0.035 for the intermediate, 95% limits of agreement − 0.056 to 0.060 for the novice).
Conclusions
RRI measurements by both an intermediate and novice sonographer in a volunteer population were reliable, accurate and precise after a brief course. RRI is easy to learn and feasible within the scope of point-of-care ultrasound.
The automatic TBP device is reliable for measuring low pressures and thus for exclusion of critical limb ischemia in patients with diabetes. After algorithm adjustment the device's reliability appears to be acceptable in the entire spectrum of TBP values. TBP appears to have less inter and intraobserver variability than what is reported for ABP.
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