Kapka T. Miteva (Switzerland)
University of Geneva Division of CardiologyAuthor Of 1 Presentation
O065 - Single-Cell Analysis Uncovers Osteoblast Factor GDF10 as Mediator of Vascular Smooth Muscle Cell Phenotypic Modulation Associated with Plaque Rupture in Human Carotid Artery Disease (ID 665)
Abstract
Background and Aims
Vascular smooth muscle cells (VSMC) are not terminally differentiated and undergo complex phenotypic changes during atherosclerosis. However, the complex heterogeneity of VSMC and how VSMC de-differentiation affects human carotid artery disease (CAD) risk has not been clearly established. The aim of the present study is to comprehensively characterized the transcriptomic profile of phenotypically modulated VSMC and to identify mediators of VSMC transition to osteogenic like cells with likely detrimental role for atherosclerosis plaque stability.
Methods
Single-cell RNA sequencing of CD45 negative cells derived from Apoe-/- mice on a normal (NCD) or high cholesterol diet (HCD) was performed. To confirm the identified marker mediator of VSMC transition to osteogenic like cells, immunofluorescence staining of aortic roots of VSMC lineage tracing Apoe-/- Myh11-CreERT2, ROSA26 STOP-flox eYFP+/+ mice fed an NCD or HCD and of internal carotid plaque specimens from symptomatic and asymptomatic patients with CAD was used. VSMC osteogenic switch was quantified upon GDF10 and oxLDL stimulation by flow cytometry.
Results
Disease-relevant gene signature of VSMC macrophagic calcific phenotype, VSMC mesenchymal chondrogenic phenotype, VSMC inflammatory and fibro phenotype and VSMC inflammatory phenotype was revealed. The osteoblast factor GDF10 was highly expressed in phenotypically modified VSMC clusters, in parallel GDF10 stimulation in combination with oxLDL triggered VSMC osteogenic switch in vitro. Moreover, higher GDF10 expression in phenotypically modified VSMC in human atherosclerotic plaques was associated with an increased risk of plaque rupture in CAD patients.
Conclusions
Osteoblast factor GDF10 is associated with VSMC transition to osteogenic like cells with likely detrimental role in atherosclerosis plaque stability.
Presenter of 1 Presentation
O065 - Single-Cell Analysis Uncovers Osteoblast Factor GDF10 as Mediator of Vascular Smooth Muscle Cell Phenotypic Modulation Associated with Plaque Rupture in Human Carotid Artery Disease (ID 665)
Abstract
Background and Aims
Vascular smooth muscle cells (VSMC) are not terminally differentiated and undergo complex phenotypic changes during atherosclerosis. However, the complex heterogeneity of VSMC and how VSMC de-differentiation affects human carotid artery disease (CAD) risk has not been clearly established. The aim of the present study is to comprehensively characterized the transcriptomic profile of phenotypically modulated VSMC and to identify mediators of VSMC transition to osteogenic like cells with likely detrimental role for atherosclerosis plaque stability.
Methods
Single-cell RNA sequencing of CD45 negative cells derived from Apoe-/- mice on a normal (NCD) or high cholesterol diet (HCD) was performed. To confirm the identified marker mediator of VSMC transition to osteogenic like cells, immunofluorescence staining of aortic roots of VSMC lineage tracing Apoe-/- Myh11-CreERT2, ROSA26 STOP-flox eYFP+/+ mice fed an NCD or HCD and of internal carotid plaque specimens from symptomatic and asymptomatic patients with CAD was used. VSMC osteogenic switch was quantified upon GDF10 and oxLDL stimulation by flow cytometry.
Results
Disease-relevant gene signature of VSMC macrophagic calcific phenotype, VSMC mesenchymal chondrogenic phenotype, VSMC inflammatory and fibro phenotype and VSMC inflammatory phenotype was revealed. The osteoblast factor GDF10 was highly expressed in phenotypically modified VSMC clusters, in parallel GDF10 stimulation in combination with oxLDL triggered VSMC osteogenic switch in vitro. Moreover, higher GDF10 expression in phenotypically modified VSMC in human atherosclerotic plaques was associated with an increased risk of plaque rupture in CAD patients.
Conclusions
Osteoblast factor GDF10 is associated with VSMC transition to osteogenic like cells with likely detrimental role in atherosclerosis plaque stability.