Microplastics (MPs) are an everyday part of life, and are now ubiquitous in the environment. Crucially, MPs have not just been found within the environment, but also within human bodies, including the blood. We aimed to provide novel information on the range of MP polymer types present, as well as their size and shape characteristics, in human whole blood from 20 healthy volunteers. Twenty-four polymer types were identified from 18 out of 20 (90 %) donors and quantified in blood, with the majority observed for the first time. Using an LOQ approach, five polymer types met the threshold with a lower mean ± SD of 2466 ± 4174 MP/L. The concentrations of plastics analysed in blood samples ranged from 1.84 - 4.65 μg/mL. Polyethylene (32 %), ethylene propylene diene (14 %), and ethylene-vinyl-acetate/alcohol (12 %) fragments were the most abundant. MP particles that were identified within the blood samples had a mean particle length of 127.99 ± 293.26 µm (7-3000 µm), and a mean particle width of 57.88 ± 88.89 µm (5-800 µm). The MPs were predominantly categorised as fragments (88 %) and were white/clear (79 %). A variety of plastic additive chemicals were identified including endocrine disrupting-classed phthalates. The procedural blank samples comprised 7 polymer types, that were distinct from those identified in blood, mainly resin (25 %), polyethylene terephthalate (17 %), and polystyrene (17 %) with a mean ± SD of 4.80 ± 5.59 MP/L. This study adds to the growing evidence that MPs are taken up into the human body and are transported via the bloodstream. The shape and sizes of the particles raise important questions with respect to their presence and associated hazards in terms of potential detrimental impacts such as vascular inflammation, build up within major organs, and changes to either immune cell response, or haemostasis and thrombosis.

Prostacyclin (PGI₂) modulates platelet activation to regulate haemostasis. Evidence has emerged to suggest that thrombi are dynamic structures with distinct areas of differing platelet activation. It was hypothesised that PGI₂ could reverse platelet spreading by actin cytoskeletal modulation, leading to reduced capability of platelet aggregates to withstand a high shear environment. Our data demonstrates that post-flow of PGI₂ over activated and spread platelets on fibrinogen, identified a significant reduction in platelet surface area under high shear. Exploration of the molecular mechanisms underpinning this effect revealed that PGI₂ reversed stress fibre formation in adherent platelets, reduced platelet spreading, whilst simultaneously promoting actin nodule formation. The effects of PGI₂ on stress fibres were mimicked by the adenylyl cyclase activator forskolin and prevented by inhibitors of protein kinase A (PKA). Stress fibre formation is a RhoA dependent process and we found that treatment of adherent platelets with PGI₂ caused inhibitory phosphorylation of RhoA, reduced RhoA GTP-loading and reversal of myosin light chain phosphorylation. Phospho-RhoA was localised in actin nodules with PKA type II and a number of other phosphorylated PKA substrates. This study demonstrates that PGI₂ can reverse key platelet functions after their initial activation and identifies a novel mechanism for controlling thrombosis.

Quantum dots (QDs) are semi-conducting nanoparticles that have been developed for a range of biological and non-biological functions. They can be tuned to multiple different emission wavelengths and can have significant benefits over other fluorescent systems. Many studies have utilised QDs with a cadmium-based core; however, these QDs have since been shown to have poor biological compatibility. Therefore, other QDs, such as indium phosphide QDs, have been developed. These QDs retain excellent fluorescent intensity and tunability but are thought to have elevated biological compatibility. Herein we discuss the applicability of a range of QDs to the cardiovascular system. Key disease states such as myocardial infarction and stroke are associated with cardiovascular disease (CVD), and there is an opportunity to improve clinical imaging to aide clinical outcomes for these disease states. QDs offer potential clinical benefits given their ability to perform multiple functions, such as carry an imaging agent, a therapy, and a targeting motif. Two key cell types associated with CVD are platelets and immune cells. Both cell types play key roles in establishing an inflammatory environment within CVD, and as such aid the formation of pathological thrombi. However, it is unclear at present how and with which cell types QDs interact, and if they potentially drive unwanted changes or activation of these cell types. Therefore, although QDs show great promise for boosting imaging capability, further work needs to be completed to fully understand their biological compatibility.

Quantum dots (QDs) are semiconducting inorganic nanocrystals, that have garnered interest in biological and medical spheres, due to their potential benefits in biomedical imaging and drug-delivery systems.

Evidence has emerged to suggest that thrombi are dynamic structures with distinct areas of differing platelet activation and inhibition. We hypothesised that Nitric oxide (NO), a platelet inhibitor, can modulate the actin cytoskeleton reversing platelet spreading, and therefore reduce the capability of thrombi to withstand a high shear environment. Our data demonstrates that GSNO, DEANONOate, and a PKG-activating cGMP analogue reversed stress fibre formation and increased actin nodule formation in adherent platelets. This effect is sGC dependent and independent of ADP and thromboxanes. Stress fibre formation is a RhoA dependent process and NO induced RhoA inhibition, however, it did not phosphorylate RhoA at ser188 in spread platelets. Interestingly NO and PGI₂ synergise to reverse stress fibre formation at physiologically relevant concentrations. Analysis of high shear conditions indicated that platelets activated on fibrinogen, induced stress fibre formation, which was reversed by GSNO treatment. Furthermore, preformed thrombi on collagen post perfused with GSNO had a 30% reduction in thrombus height in comparison to the control. This study demonstrates that NO can reverse key platelet functions after their initial activation and identifies a novel mechanism for controlling excessive thrombosis.

Approximately 17.3% of the global population exhibits an element of zinc (Zn²⁺) deficiency. One symptom of Zn²⁺ deficiency is increased bleeding through impaired hemostasis. Platelets are crucial to hemostasis and are inhibited by endothelial-derived prostacyclin (prostaglandin I₂ [PGI₂]), which signals via adenylyl cyclase (AC) and cyclic adenosine monophosphate signaling. In other cell types, Zn²⁺ modulates cyclic adenosine monophosphate concentrations by changing AC and/or phosphodiesterase activity. To investigate if Zn²⁺ can modulate platelet PGI₂ signaling. Platelet aggregation, spreading, and western blotting assays with Zn²⁺ chelators and cyclic nucleotide elevating agents were performed in washed platelets and platelet-rich plasma conditions. In vitro thrombus formation with various Zn²⁺ chelators and PGI₂ was assessed in whole blood. Incubation of whole blood or washed platelets with Zn²⁺ chelators caused either embolization of preformed thrombi or reversal of platelet spreading, respectively. To understand this effect, we analyzed resting platelets and identified that incubation with Zn²⁺ chelators elevated pVASP^ser157, a marker of PGI₂ signaling. In agreement that Zn²⁺ affects PGI₂ signaling, addition of the AC inhibitor SQ22536 blocked Zn²⁺ chelation-induced platelet spreading reversal, while addition of Zn²⁺ blocked PGI₂-mediated platelet reversal. Moreover, Zn²⁺ specifically blocked forskolin-mediated AC reversal of platelet spreading. Finally, PGI₂ inhibition of platelet aggregation and in vitro thrombus formation was potentiated in the presence of low doses of Zn²⁺ chelators, increasing its effectiveness in inducing platelet inhibition. Zn²⁺ chelation potentiates platelet PGI₂ signaling, elevating PGI₂'s ability to prevent effective platelet activation, aggregation, and thrombus formation.