Human and murine fibroblast single cell transcriptomics reveals fibroblast clusters are differentially affected by ageing, and serum cholesterol

Aims Specific fibroblast markers and in-depth heterogeneity analysis are currently lacking, hindering functional studies in cardiovascular diseases (CVDs). Here, we established cell-type markers and heterogeneity in murine and human arteries and studied the adventitial fibroblast response to CVD and its risk factors hypercholesterolaemia and ageing. Methods and results Murine aorta single-cell RNA-sequencing analysis of adventitial mesenchymal cells identified fibroblast-specific markers. Immunohistochemistry and flow cytometry validated platelet-derived growth factor receptor alpha (PDGFRA) and dipeptidase 1 (DPEP1) across human and murine aorta, carotid, and femoral arteries, whereas traditional markers such as the cluster of differentiation (CD)90 and vimentin also marked transgelin+ vascular smooth muscle cells. Next, pseudotime analysis showed multiple fibroblast clusters differentiating along trajectories. Three trajectories, marked by CD55 (Cd55+), Cxcl chemokine 14 (Cxcl14+), and lysyl oxidase (Lox+), were reproduced in an independent RNA-seq dataset. Gene ontology (GO) analysis showed divergent functional profiles of the three trajectories, related to vascular development, antigen presentation, and/or collagen fibril organization, respectively. Trajectory-specific genes included significantly more genes with known genome-wide associations (GWAS) to CVD than expected by chance, implying a role in CVD. Indeed, differential regulation of fibroblast clusters by CVD risk factors was shown in the adventitia of aged C57BL/6J mice, and mildly hypercholesterolaemic LDLR KO mice on chow by flow cytometry. The expansion of collagen-related CXCL14+ and LOX+ fibroblasts in aged and hypercholesterolaemic aortic adventitia, respectively, coincided with increased adventitial collagen. Immunohistochemistry, bulk, and single-cell transcriptomics of human carotid and aorta specimens emphasized translational value as CD55+, CXCL14+ and LOX+ fibroblasts were observed in healthy and atherosclerotic specimens. Also, trajectory-specific gene sets are differentially correlated with human atherosclerotic plaque traits. Conclusion We provide two adventitial fibroblast-specific markers, PDGFRA and DPEP1, and demonstrate fibroblast heterogeneity in health and CVD in humans and mice. Biological relevance is evident from the regulation of fibroblast clusters by age and hypercholesterolaemia in vivo, associations with human atherosclerotic plaque traits, and enrichment of genes with a GWAS for CVD

Editor's Choice – European Society for Vascular Surgery (ESVS) 2023 Clinical Practice Guidelines on the Management of Atherosclerotic Carotid and Vertebral Artery Disease

info:eu-repo/semantics/publishedVersio

Towards individualized follow-up protocols after endovascular aortic aneurysm repair

Endovascular aneurysm repair (EVAR) has become the primary treatment option for elective abdominal aortic aneurysms. However, a significant number of patients require secondary interventions to maintain adequate aneurysm exclusion and ultimately prevent death from abdominal aortic aneurysm (AAA) rupture. To maintain success and offer timely secondary intervention, intensive image surveillance has been recommended. These rigorous surveillance regimens are costly and may have deleterious effects from radiation and contrast exposure. Improvements in patient selection, operative technique and devices have caused a decline in complications after EVAR. Therefore, there is a need to reduce surveillance after EVAR for patients at lower risk of complications and install individualized follow-up protocols. This review describes the current strategies for surveillance and clarification of risk factors and predictors for late complications and discusses proposed risk-adapted strategies for postoperative surveillance after EVAR

Application of an adaptive polynomial chaos expansion on computationally expensive three-dimensional cardiovascular models for uncertainty quantification and sensitivity analysis

When applying models to patient-specific situations, the impact of model input uncertainty on the model output uncertainty has to be assessed. Proper uncertainty quantification (UQ) and sensitivity analysis (SA) techniques are indispensable for this purpose. An efficient approach for UQ and SA is the generalized polynomial chaos expansion (gPCE) method, where model response is expanded into a finite series of polynomials that depend on the model input (i.e., a meta-model). However, because of the intrinsic high computational cost of three-dimensional (3D) cardiovascular models, performing the number of model evaluations required for the gPCE is often computationally prohibitively expensive. Recently, Blatman and Sudret (2010, “An Adaptive Algorithm to Build Up Sparse Polynomial Chaos Expansions for Stochastic Finite Element Analysis,” Probab. Eng. Mech., 25(2), pp. 183–197) introduced the adaptive sparse gPCE (agPCE) in the field of structural engineering. This approach reduces the computational cost with respect to the gPCE, by only including polynomials that significantly increase the meta-model’s quality. In this study, we demonstrate the agPCE by applying it to a 3D abdominal aortic aneurysm (AAA) wall mechanics model and a 3D model of flow through an arteriovenous fistula (AVF). The agPCE method was indeed able to perform UQ and SA at a significantly lower computational cost than the gPCE, while still retaining accurate results. Cost reductions ranged between 70–80% and 50–90% for the AAA and AVF model, respectively

Editor's Choice – European Society for Vascular Surgery (ESVS) 2023 Clinical Practice Guidelines on Antithrombotic Therapy for Vascular Diseases

The European Society for Vascular Surgery (ESVS) has developed a series of clinical practice guidelines for clinicians caring for patients with vascular diseases. This is the first guideline specifically examining antithrombotic therapy. The aim of the guideline is to assist clinicians and patients in selecting an optimal antithrombotic strategy.</p