Microplastics (MPs) are ubiquitous in the environment, in the human food chain, and have been recently detected in blood and lung tissues. To undertake a pilot analysis of MP contamination in human vein tissue samples with respect to their presence (if any), levels, and characteristics of any particles identified. This study analysed digested human saphenous vein tissue samples (n = 5) using μFTIR spectroscopy (size limitation of 5 μm) to detect and characterise any MPs present. In total, 20 MP particles consisting of five MP polymer types were identified within 4 of the 5 vein tissue samples with an unadjusted average of 29.28 ± 34.88 MP/g of tissue (expressed as 14.99 ± 17.18 MP/g after background subtraction adjustments). Of the MPs detected in vein samples, five polymer types were identified, of irregular shape (90%), with alkyd resin (45%), poly (vinyl propionate/acetate, PVAc (20%) and nylon-ethylene-vinyl acetate, nylon-EVA, tie layer (20%) the most abundant. While the MP levels within tissue samples were not significantly different than those identified within procedural blanks (which represent airborne contamination at time of sampling), they were comprised of different plastic polymer types. The blanks comprised n = 13 MP particles of four MP polymer types with the most abundant being polytetrafluoroethylene (PTFE), then polypropylene (PP), polyethylene terephthalate (PET) and polyfumaronitrile:styrene (FNS), with a mean ± SD of 10.4 ± 9.21, p = 0.293. This study reports the highest level of contamination control and reports unadjusted values alongside different contamination adjustment techniques. This is the first evidence of MP contamination of human vascular tissues. These results support the phenomenon of transport of MPs within human tissues, specifically blood vessels, and this characterisation of types and levels can now inform realistic conditions for laboratory exposure experiments, with the aim of determining vascular health impacts.

Transport of LDL (low-density lipoprotein) from plasma to arterial intima is thought to be rate limiting in the development of atherosclerosis. Its variation likely determines where lesions develop within arteries and might account for some of the currently unexplained difference in disease susceptibility between individuals. It may also be critical in the development of lipid-rich, unstable plaques. Mechanisms have been controversial but recent evidence suggests that caveolar transcytosis across endothelial cells is the dominant pathway. Receptors involved are LDLR (LDL receptor), SR-B1 (scavenger receptor class B type 1), and ALK1 (activin receptor-like kinase 1). The role of LDLR is influenced by IL-1β (interleukin-1β); the role of SR-B1 by HDL (high-density lipoprotein), DOCK4 (dedicator of cytokinesis 4), GPER (G-protein–coupled estrogen receptor), and HMGB1 (high mobility group box 1); and the role of ALK1 by BMP (bone morphogenetic protein) 9. Additionally, BMP4 stimulates transcytosis and FSTL1 (follistatin-like 1 protein) inhibits it. Fundamental transcytotic mechanisms include caveola formation, undocking, trafficking, and docking; they are influenced by cholesterol-lowering agents, MYDGF (myeloid-derived growth factor), MFSD2a (major facilitator superfamily domain containing 2a) in the blood-brain barrier, and inhibitors of dynamin-2 and tubulin polymerization. The relative merits of different therapeutic approaches are discussed, with statins, colchicine, benzimidazoles, and metformin being existing drugs that might be repurposed and salidroside and glycyrrhizic acid being nutraceuticals worth investigating. Finally, we discuss evidence against the ferry-boat model of transcytosis, the contributions of receptor-mediated, fluid-phase, and active transcytosis, and where inhibition of transcytosis might be most beneficial.

Unresolved hyperglycaemia, a hallmark of type 2 diabetes mellitus (T2DM), is a well characterised manifestation of altered fuel homeostasis and our understanding of its role in the pathologic activation of the inflammatory system continues to grow. Metabolic disorders like T2DM trigger changes in the regulation of key cellular processes such as cell trafficking and proliferation, and manifest as chronic inflammatory disorders with severe long-term consequences. Activation of inflammatory pathways has recently emerged as a critical link between T2DM and inflammation. A substantial body of evidence has suggested that this is due in part to increased flux through the hexosamine biosynthetic pathway (HBP). The HBP, a unique nutrient-sensing metabolic pathway, produces the activated amino sugar UDP-GlcNAc which is a critical substrate for protein O-GlcNAcylation, a dynamic, reversible post-translational glycosylation of serine and threonine residues in target proteins. Protein O-GlcNAcylation impacts a range of cellular processes, including inflammation, metabolism, trafficking, and cytoskeletal organisation. As increased HBP flux culminates in increased protein O-GlcNAcylation, we propose that targeting O-GlcNAcylation may be a viable therapeutic strategy for the prevention and management of glucose-dependent pathologies with inflammatory components.

Protein O-GlcNAcylation, a dynamic and reversible glucose-dependent post-translational modification of serine and threonine residues on target proteins, has been proposed to promote vascular smooth muscle cell proliferation and migration events implicated in vein graft failure (VGF). Therefore, targeting the enzymes (glutamine fructose-6P amidotransferase (GFAT), O-GlcNAc transferase (OGT), and O-GlcNAcase (OGA)) that regulate cellular O-GlcNAcylation could offer therapeutic options to reduce neointimal hyperplasia and venous stenosis responsible for VGF. However, it is unclear how type 2 diabetes mellitus (T2DM) and hyperglycaemia affect the expression of these enzymes in human saphenous vein smooth muscle cells (HSVSMCs), a key cell type involved in the vascular dysfunction responsible for saphenous VGF. Therefore, our aim was to assess whether T2DM and hyperglycaemia affect GFAT, OGT, and OGA expression levels in HSVSMCs in vitro. Expression levels of GFAT, OGT, and OGA were determined in low-passage HSVSMCs from T2DM and non-T2DM patients, and in HSVSMCs treated for 48 h with hyperglycaemic (10 mM and 25 mM) glucose concentrations, by quantitative immunoblotting. Expression levels of OGT, OGA, and GFAT were not significantly different in HSVSMC lysates from T2DM patients versus non-T2DM controls. In addition, treatment with high glucose concentrations (10 mM and 25 mM) had no significant effect on the protein levels of these enzymes in HSVSMC lysates. From our findings, T2DM and hyperglycaemia do not significantly impact the expression levels of the O-GlcNAcylation-regulating enzymes OGT, OGA, and GFAT in HSVSMCs. This study provides a foundation for future studies to assess the role of O-GlcNAcylation on VGF in T2DM.