Extracellular vesicles secreted by Saccharomyces cerevisiae are involved in cell wall remodelling

Extracellular vesicles (EVs) are membranous vesicles that are released by cells. In this study, the role of the Endosomal Sorting Complex Required for Transport (ESCRT) machinery in the biogenesis of yeast EVs was examined. Knockout of components of the ESCRT machinery altered the morphology and size of EVs as well as decreased the abundance of EVs. In contrast, strains with deletions in cell wall biosynthesis genes, produced more EVs than wildtype. Proteomic analysis highlighted the depletion of ESCRT components and enrichment of cell wall remodelling enzymes, glucan synthase subunit Fks1 and chitin synthase Chs3, in yeast EVs. Interestingly, EVs containing Fks1 and Chs3 rescued the yeast cells from antifungal molecules. However, EVs from fks1∆ or chs3∆ or the vps23∆chs3∆ double knockout strain were unable to rescue the yeast cells as compared to vps23∆ EVs. Overall, we have identified a potential role for yeast EVs in cell wall remodelling.Kening Zhao, Mark Bleackley, David Chisanga, Lahiru Gangoda, Pamali Fonseka, Michael Liem, Hina Kalra, Haidar Al Saffar, Shivakumar Keerthikumar, Ching-Seng Ang, Christopher G. Adda, Lanzhou Jiang, Kuok Yap, Ivan K. Poon, Peter Lock, Vincent Bulone, Marilyn Anderson, Suresh Mathivana

Endothelial shear stress plays a key role in acute coronary syndromes with intact fibrous cap (plaque erosion): a computational fluid dynamics and optical coherence tomography study

Cardiovascular Aspects of Radiolog

High endothelial shear stress and stress gradient at plaque erosion persist up to 12 months

Background: Local hemodynamics are known to play an important role in the development of plaque erosion. Recent studies showed that erosion patients might be treated conservatively without stent implantation. We investigated evolution of hemodynamic parameters on the plaque erosion site in conservatively treated patients.Methods: Computational fluid dynamics (CFD) simulations were performed using the coronary angiogram and optical coherence tomography (OCT) images of non-stent treated erosion patients who had serial OCT studies. Calculated CFD parameters included endothelial shear stress (ESS), ESS gradient (ESSG), and oscillatory shear index (OSI).Results: The CFD parameters at the erosion and non-erosion sites were compared among baseline (n = 23), and 1-month (n = 20) and 12-month (n = 16) follow-ups. The erosion site had higher ESS and ESSG values than the non-erosion sites at baseline (mean ESS: 3.00 vs 1.36 Pa, p < 0.01; mean ESSG: 1.71 vs. 0.65 Pa/mm, p = 0.01), 1-month (mean ESS: 2.89 vs 1.19 Pa, p < 0.01; mean ESSG: 1.71 vs. 0.60 Pa/mm, p < 0.01), and 12-month (mean ESS: 3.26 vs 1.59 Pa, p < 0.01; mean ESSG: 1.87 vs. 0.78 Pa/mm, p < 0.01). OSI was not different between erosion and and non-erosion sites.Conclusions: ESS and ESSG values were higher at the plaque erosion sites compared to non-erosion sites. Elevated ESS and ESSG at the erosion site persisted up to 12 months. These data indicate that a local thrombogenic milieu related to hemodynamic perturbation persists up to 12 months at the plaque erosion sites following conservative treatment

High endothelial shear stress and stress gradient at plaque erosion persist up to 12 months

Background: Local hemodynamics are known to play an important role in the development of plaque erosion. Recent studies showed that erosion patients might be treated conservatively without stent implantation. We investigated evolution of hemodynamic parameters on the plaque erosion site in conservatively treated patients.Methods: Computational fluid dynamics (CFD) simulations were performed using the coronary angiogram and optical coherence tomography (OCT) images of non-stent treated erosion patients who had serial OCT studies. Calculated CFD parameters included endothelial shear stress (ESS), ESS gradient (ESSG), and oscillatory shear index (OSI).Results: The CFD parameters at the erosion and non-erosion sites were compared among baseline (n = 23), and 1-month (n = 20) and 12-month (n = 16) follow-ups. The erosion site had higher ESS and ESSG values than the non-erosion sites at baseline (mean ESS: 3.00 vs 1.36 Pa, p < 0.01; mean ESSG: 1.71 vs. 0.65 Pa/mm, p = 0.01), 1-month (mean ESS: 2.89 vs 1.19 Pa, p < 0.01; mean ESSG: 1.71 vs. 0.60 Pa/mm, p < 0.01), and 12-month (mean ESS: 3.26 vs 1.59 Pa, p < 0.01; mean ESSG: 1.87 vs. 0.78 Pa/mm, p < 0.01). OSI was not different between erosion and and non-erosion sites.Conclusions: ESS and ESSG values were higher at the plaque erosion sites compared to non-erosion sites. Elevated ESS and ESSG at the erosion site persisted up to 12 months. These data indicate that a local thrombogenic milieu related to hemodynamic perturbation persists up to 12 months at the plaque erosion sites following conservative treatment.Radiolog

High spatial endothelial shear stress gradient independently predicts site of acute coronary plaque rupture and erosion

Aims To investigate local haemodynamics in the setting of acute coronary plaque rupture and erosion.Methods and results Intracoronary optical coherence tomography performed in 37 patients with acute coronary syndromes caused by plaque rupture (n=19) or plaque erosion (n=18) was used for three-dimensional reconstruction and computational fluid dynamics simulation. Endothelial shear stress (ESS), spatial ESS gradient (ESSG), and oscillatory shear index (OSI) were compared between plaque rupture and erosion through mixed-effects logistic regression. Lipid, calcium, macrophages, layered plaque, and cholesterol crystals were also analysed. By multivariable analysis, only high ESSG [odds ratio (OR) 5.29, 95% confidence interval (CI) 2.57-10.89, P<0.001], lipid (OR 12.98, 95% CI 6.57-25.67, P<0.001), and layered plaque (OR 3.17, 95% CI 1.82-5.50, P<0.001) were independently associated with plaque rupture. High ESSG (OR 13.28, 95% CI 6.88-25.64, P<0.001), ESS (OR 2.70, 95% CI 1.34-5.42, P=0.005), and OSI (OR 2.18, 95% CI 1.33-3.54, P=0.002) independently associated with plaque erosion. ESSG was higher at rupture sites than erosion sites [median (interquartile range): 5.78 (2.47-21.15) vs. 2.62 (1.44-6.18) Pa/mm, P=0.009], OSI was higher at erosion sites than rupture sites [1.04 x 10(-2) (2.3 x 10(-3)-4.74 x 10(-2)) vs. 1.29 x 10(-3) (9.39 x 10(-5)-3.0 x 10(-2)), P<0.001], but ESS was similar (P=0.29).Conclusions High ESSG is independently associated with plaque rupture while high ESSG, ESS, and OSI associate with plaque erosion. While ESSG is higher at rupture sites than erosion sites, OSI is higher at erosion sites and ESS was similar. These results suggest that ESSG and OSI may play critical roles in acute plaque rupture and erosion, respectively.Cardiovascular Aspects of Radiolog