Biology subjects

Lally, C.

Publications and source records attributed to Lally, C..

3 recordsLinked to original sources

bioRxiv2020

An investigation into the critical role of fibre orientation in the ultimate tensile strength and stiffness of human carotid plaque caps

The development and subsequent rupture of atherosclerotic plaques in human carotid arteries is a major cause of ischemic stroke. Mechanical characterization of atherosclerotic plaques can aid our understanding of this rupture risk. Despite this however, experimental studies on human atherosclerotic carotid plaques, and fibrous plaque caps in particular, are very limited. This study aims to provide further insights into atherosclerotic plaque rupture by mechanically testing human fibrous plaque caps, the region of the atherosclerotic lesion most often attributed the highest risk of rupture. The results obtained highlight the variability in the ultimate tensile stress, strain and stiffness experienced in atherosclerotic plaque caps. By pre-screening all samples using small angle light scattering (SALS) to determine the dominant fibre direction in the tissue, along with supporting histological analysis, this work suggests that the collagen fibre alignment in the circumferential direction plays the most dominant role for determining plaque structural stability. The work presented in this study could provide the basis for new diagnostic approaches to be developed, which non-invasively identify carotid plaques at greatest risk of rupture. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=95 SRC="FIGDIR/small/264457v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@185109forg.highwire.dtl.DTLVardef@1067820org.highwire.dtl.DTLVardef@1b8baf3org.highwire.dtl.DTLVardef@f9b3af_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2020

Diffusion tensor imaging and arterial tissue: establishing the influence of arterial tissue microstructure on fractional anisotropy, mean diffusivity and tractography

In this study we investigated the potential of diffusion tensor imaging (DTI) for providing insight into microstructural changes in arterial tissue by exploring the influence that cell, collagen and elastin content have on fractional anisotropy (FA), mean diffusivity (MD) and tractography. Five ex vivo porcine carotid artery models (n = 6 vessels each) - native, fixed native, collagen degraded, elastin degraded and decellularised - were developed to selectively remove components of arterial microstructure. Intact vessels were imaged at 7 T using a DTI protocol with b = 0 and 800 s/mm2 and 10 isotopically distributed directions. FA and MD values were evaluated in the medial layer of vessels and compared across tissue models. FA values measured in native and fixed native vessels were significantly higher (p<0.0001) than those in the elastin degraded and decellularised arteries. Collagen degraded vessels had a significantly higher (p<0.01) FA than elastin degraded and decellularised vessels. Native and fixed vessels had significantly lower (p<0.0001) MD values than elastin degraded, while the MD in decellularised arteries was significantly higher than that in both native (p<0.01) and fixed (p<0.005) tissue. Significantly lower (p<0.005) MD was measured in collagen degraded compared with the elastin degraded model. Tractography results yielded similar helically arranged tracts for native and collagen degraded vessels, whilst elastin degraded and decellularised vessels showed no consistent tracts. FA, MD and tractography were found to be highly sensitive to changes in the microstructural composition of arterial tissue, with cell content being a dominant source of the measured anisotropy in the vessel wall.

bioengineering↗

bioRxiv2020

The calcium binding protein S100β marks Hedgehog-responsive perivascular stem cells that contribute to intimal thickening following iatrogenic flow restriction

A hallmark of subclinical atherosclerosis is the accumulation of vascular smooth muscle cell (SMC)-like cells leading to intimal thickening. While medial SMCs contribute, the participation of hedgehog responsive resident vascular stem cells (vSCs) to lesion formation remains unclear. Using transgenic eGFP mice and genetic lineage tracing of S100{beta} vSCs in vivo, we identified S100{beta}/Sca1 cells derived from a S100{beta} non-SMC parent population within lesions that co-localise with smooth muscle -actin (SMA) cells following iatrogenic flow restriction, an effect attenuated following hedgehog inhibition with the smoothened inhibitor, cyclopamine. In vitro, S100{beta}/Sca1 cells isolated from atheroprone regions of the mouse aorta expressed hedgehog signalling components, acquired the di-methylation of histone 3 lysine 4 (H3K4me2) stable SMC epigenetic mark at the Myh11 locus and underwent myogenic differentiation in response to recombinant sonic hedgehog (SHh). Both S100{beta} and PTCH1 cells were present in human vessels while S100{beta} cells were enriched in arteriosclerotic lesions. Recombinant SHh promoted myogenic differentiation of human induced pluripotent stem cell-derived S100{beta} neuroectoderm progenitors In vitro. We conclude that hedgehog responsive S100{beta} vSCs contribute to lesion formation and support targeting hedgehog signalling to treat subclinical arteriosclerosis.

cell biology↗