Biology subjects

Alarcon, M.

Publications and source records attributed to Alarcon, M..

3 recordsLinked to original sources

bioRxiv2026

Umbilical-brain endothelial communication via TSP-1 is linked with reduced brain angiogenesis in offspring of preeclampsia

BackgroundPreeclampsia, a maternal hypertensive syndrome affect fetal brain development and cerebral angiogenesis, with potential acute and long-term consequences. Underlying mechanisms of these brain vascular alterations are unknown. This study investigates the role of thrombospondin-1 (TSP-1), an antiangiogenic glycoprotein, as a key mediator of communication between the fetoplacental and fetal brain endothelium in the context of preeclampsia. MethodsConditioned media (CM) of human umbilical vein endothelial cells (HUVECs) from normal pregnancies (NP-CM) and preeclamptic pregnancies (PE-CM), were used to treat human (hCMEC/D3) and murine brain microvascular endothelial cells (BMECs). A proteomic analysis was performed in plasma of the umbilical cord of normal pregnancy and preeclampsia. TSP-1 was identify using proteomic analysis and confirmed by Western blot. PE-CM depleted of TSP-1, using immunoprecipitation, was used to evaluate protein-protein interaction with vascular endothelial growth factor (VEGF). Antibody-mediated blockage of TSP-1 was used to investigate antiangiogenic effect and pro-angiogenic signaling pathways in brain endothelial cells exposed to PE-CM. ResultsPE-CM significantly reduced angiogenesis, migration, and invasion of brain endothelial cells and altered cytoskeletal organization. These effects were accompanied by reduced VEGFR2 and AKT signaling, indicating impaired angiogenic pathways. Proteomic analysis of umbilical cord plasma revealed elevated TSP-1 levels in preeclampsia, which was confirmed by Western blotting. TSP-1 was also increased in PE-CM, and immunoprecipitation assays suggested a protein-protein interaction with VEGF. Antibody-mediated blockade of TSP-1 restored angiogenesis, as reflected by increased total tube length, and rescued VEGFR2 and AKT signaling in brain endothelial cells exposed to PE-CM. ConclusionTSP-1-mediated endothelium-endothelium communication between placenta-brain axis in offspring of mothers with preeclampsia. This communication mediated by TSP-1 may contribute to acute and long-lasting cerebrovascular dysfunction observed in infants exposed to preeclampsia.

physiology↗

bioRxiv2025

Circulating Microplastics as Acute Triggers of Platelet Activation and Coagulation: Implications for Cardiovascular Risk

BackgroundMicroplastics and nanoplastics (MPs/NPs) have recently been detected in human blood and vascular tissues, yet their direct effects on thrombosis remain poorly defined. Given the central role of platelets in atherothrombotic disease, understanding how circulating NPs exposure influences platelet function is critical for cardiovascular health. MethodsWashed platelets and citrated whole blood from healthy volunteers were exposed to fluorescent carboxylated polystyrene nanoplastics (PS-NPs; 100 nm). PS-NPs association, internalization, and activation were quantified by flow cytometry (side scatter, forward scatter, PS-NPs fluorescence, and CD63). Fluorescence microscopy visualized the PS-NPs uptake kinetics. A whole-blood coagulation assay assessed PS-NPs-induced clot formation under varying Ca{superscript 2} concentrations. ResultsPS-NPs rapidly associated with human platelets in a concentration and time-dependent manner, with near-maximal internalization achieved within 10 minutes. PS-NPs uptake induced marked structural remodeling (increased FSC/SSC), pseudopod formation, and concentration-dependent CD63 externalization, indicative of robust platelet activation comparable to that induced by thrombin stimulation. PS-NPs association remained non-saturable across tested doses (0.3-20 g), suggesting high-capacity, non-specific uptake mechanisms. In whole blood, PS-NPs induced dense fibrin clot formation exclusively under Ca{superscript 2}-permissive conditions, and PS-NPs were incorporated into fibrin networks, consistent with their role as catalytic pro-coagulant surfaces. Supernatant fluorescence confirmed PS-NPs sequestration into clots. ConclusionsPS-NPs rapidly bind and activate human platelets, promote pro-coagulant platelet phenotypes, and integrate into fibrin-rich thrombi. These findings provide mechanistic evidence that circulating MPs may function as previously unrecognized environmental cardiovascular risk factors capable of acutely enhancing thrombotic potential. Defining exposure thresholds and in vivo relevance is urgently needed to assess the cardiovascular impact of the rising human NPs burden. Clinical PerspectiveO_ST_ABSWhat Is New?C_ST_ABSO_LICirculating nanoplastics rapidly bind to human platelets through high-capacity, non-specific membrane interactions, triggering cytoskeletal remodeling, granule release, and activation pathways similar to classical agonists such as thrombin. C_LIO_LINanoplastics serve as catalytic pro-coagulant surfaces that accelerate fibrin polymerization and become structurally embedded within thrombi, providing a direct mechanistic link between environmental microplastic exposure and thrombogenesis. C_LIO_LIRapid, non-saturable platelet uptake suggests that rising global microplastic loads may proportionally increase human thrombotic susceptibility. C_LI What Are the Clinical Implications?O_LINanoplastic-induced platelet activation and clot formation identify microplastics as previously unrecognized, modifiable environmental cardiovascular risk factors with mechanistic plausibility for contributing to myocardial infarction, stroke, and microvascular thrombosis. C_LIO_LIPopulations with heightened platelet reactivity, endothelial dysfunction, or chronic inflammatory states may be particularly vulnerable to thrombotic events triggered by acute or cumulative nanoplastic exposure. C_LIO_LIPublic health efforts aimed at reducing environmental microplastic contamination and establishing exposure limits may become necessary components of cardiovascular disease prevention strategies. C_LI

biochemistry↗

bioRxiv2025

Bioinformatic analysis of placental exomiRs targeting the brain in preeclampsia

BackgroundPreeclampsia is a hypertensive disorder of pregnancy associated with systemic endothelial dysfunction and, in severe cases, maternal neurological complications. Placenta-derived exosomal microRNAs (exomiRs) mediate inter-organ communication and may contribute to neurovascular injury, but their role in maternal brain dysregulation remains unclear. MethodsWe performed systems-level bioinformatic analyses of 12 differentially expressed exomiRs (6 from early-onset and 6 from late-onset preeclampsia) to assess their potential impact on brain homeostasis. Target interactomes were examined for functional enrichment, subcellular localization, and network complexity. ExomiR targets were integrated with cerebrospinal fluid (CSF) proteomic profiles from preeclamptic women with neurological symptoms. We further evaluated regulation of blood-brain barrier (BBB) components and mapped spatial expression of target proteins across brain regions and cell types relevant to neurovascular function. ResultsEarly-and late-onset preeclampsia exomiRs displayed distinct interactomes and biological signatures. Early-onset exomiRs were linked to RNA metabolism, oxidative stress, and endothelial stability, whereas late-onset exomiRs were enriched in nitrogen metabolism and vesicle-mediated transport. Integration with CSF proteomics revealed convergence on dysregulated proteins, including MAPK8, RTN4, and YWHA family members, involved in inflammation, neurodegeneration, and axonal inhibition. Several exomiRs targeted BBB-related proteins (CLDN2, TJP1, EFNA5), suggesting coordinated barrier disruption. Spatial mapping localized these targets to endothelial cells, astrocytes, interneurons, and pyramidal neurons, implicating altered synaptic and glial regulation. ConclusionsPreeclampsia-associated exomiRs may impair maternal brain homeostasis through coordinated regulation of neurovascular, inflammatory, and synaptic pathways. These findings identify candidate molecular mediators of preeclampsia-related neurovascular dysfunction and potential biomarkers for maternal brain injury.

physiology↗