Bioinspired nanovesicles enable activated platelet–targeted delivery of tissue plasminogen activator for effective thrombolysis.

Platelets are known to be activated by exogenous zinc. Herein we discuss the potential routes for zinc entry and the role of zinc–protein interactions in platelet activation.

Pannexin-1 (Panx1) forms an anion-selective channel with a permeability up to ~1 kDa and represents a non-lytic, non-vesicular ATP release pathway in erythrocytes, leukocytes and neurons. Related connexin gap junction proteins have been reported in platelets; however, the expression and function of the pannexins remain unknown. To determine the expression and function of pannexins in human plate-lets, using molecular, cellular and functional techniques. Panx1 expression in human platelets was det-ermined using qPCR and antibody-based techniques. Contributions of Panx1 to agonist-evoked efflux of cytoplasmic calcein, Ca(2+) influx, ATP release and aggregation were assessed in washed platelets under conditions where the P2X1 receptor response was preserved (0.32 U mL(-1) apyrase). Thrombus formation in whole blood was assessed in vitro using a shear chamber assay. Two structurally unrelated and widely used Panx1 inhibitors, probenecid and carbenoxolone, were used throughout this study, at concentrations that do not affect connexin channels. PANX1, but not PANX2 or PANX3, mRNA was detected in human platelets. Furthermore, Panx1 protein is glycosylated and present on the plasma membrane of platelets, and displays weak physical association with P2X1 receptors. Panx1 inhibition blocked thrombin-evoked efflux of calcein, and reduced Ca(2+) influx, ATP release, platelet aggregation and thrombus formation under arterial shear rates in vitro. The Panx1-dependent contribution was not additive to that of P2X1 receptors. Panx1 is expressed on human platelets and amplifies Ca(2+) influx, ATP release and aggregation through the secondary activation of P2X1 receptors. We propose that Panx1 represents a novel target for the management of arterial thrombosis.

Exogenous zinc induces full aggregation of washed platelet suspensions. Zinc-induced aggregation is biphasic, suggestive of secondary signalling-mediated activation.

Background and purpose Some clinical studies have reported increased myocardial infarction in people living with HIV taking the antiretroviral abacavir sulphate (ABC). Given that clinical studies contain confounding variables (e.g. HIV status), we investigated the pharmacological impact of antiretrovirals on platelet function in HIV‐negative volunteers in order to identify mechanisms of increased cardiovascular risk. Experimental approach Platelets were isolated from healthy volunteers and HIV‐negative subjects enrolled on a Phase I clinical trial and platelet function evaluated using aggregometry and flow cytometry. In vivo platelet thromboembolism was monitored in anaesthetised mice. Key results Human platelet aggregation was unaffected by all antiretrovirals tested but ABC treatment led uniquely to increased platelet granule release. ABC also interrupted nitric oxide (NO)‐mediated inhibition of platelet aggregation and increased in vivo aggregation in mice. An alternative antiretroviral, tenofovir, did not affect platelet function. Furthermore, aggregation and activation of platelets isolated from twenty subjects taking clinically‐relevant doses of tenofovir were comparable to baseline samples. Conclusions and implications ABC can enhance platelet activation, independently of HIV status suggesting a potential pharmacological effect that is absent with tenofovir. Mechanistically, we propose that ABC enhances platelet degranulation and interrupts NO‐mediated platelet inhibition. The interaction of ABC with NO signalling is supported by data demonstrating ABC‐mediated enhancement of aggregation in vivo and in vitro responses that persist in the presence of NO. Although an association between ABC and platelet activation has not been confirmed in patients, these findings provide evidence of a mechanistic link between platelet activation and antiretroviral therapy.

Lesbian, gay, bisexual, trans and sexually/gender diverse (LGBTQ+) individuals have long been underrepresented in science, technology, engineering and mathematics (STEM) and these environments have often been portrayed as spaces in which personal identity does not matter. However, for LGBTQ+ individuals, this means suppressing their gender identity and expression and remaining closeted at work, creating an uncomfortable work environment, and this can affect their performance and mental health. Multiple reports have been published within the last decade investigating the experiences of LGBTQ+ people in science. These reports all highlight a common observation that, at some point in their time within science, the majority of individuals have experienced discrimination due to their sexual orientation or gender identity. Here, in our opinion piece, we discuss our experiences of being LGBTQ+ in bioscience, the various types of discrimination that LGBTQ+ scientists may face in academia and some of the existing initiatives and campaigns in place to combat this.