Biology subjects

Escudero, C.

Publications and source records attributed to Escudero, C..

4 recordsLinked to original sources

bioRxiv2025

Plasma, not extracellular vesicles, disrupts the blood-brain barrier in eclampsia.

BackgroundEclampsia is a severe complication of preeclampsia involving blood-brain barrier (BBB) disruption. While small extracellular vesicles (sEVs) contribute to endothelial dysfunction in preeclampsia, their role in eclampsia remains unclear. Magnesium sulfate (MgSO), the standard treatment, may mitigate BBB injury. We examined the effects of plasma and plasma-derived sEVs from women with eclampsia on BBB integrity and the potential modulatory role of MgSO. MethodsPlasma and plasma-sEVs were isolated from women with normotensive pregnancies (n=18), preeclampsia (n=19), preeclampsia with organ complications (n=17), and eclampsia (n=20). An in vitro BBB model based on the culture of human brain endothelial cells was used to evaluate electrical resistance (TEER), Dextran 70 kDa permeability, and cytoskeletal alterations in the presence of womens plasmas or plasma-sEVs. The uptake of fluorescently labeled sEVs in the absence or pretreatment (-3 h) with MgSO, and sEVs cargo of relevant proteins involved in BBB regulation, were analyzed. ResultsPlasma from women with eclampsia disrupted the BBB, with marked reductions in TEER and increased permeability compared to normotensive controls, preeclampsia, and preeclampsia with organ complications. In contrast, plasma-sEVs of women with eclampsia caused less BBB impairment than plasma-sEVs from normotensive controls or preeclampsia, correlating with reduced sEVs uptake by brain endothelial cells. Lower levels of eNOS and TNF- in eclampsia-derived sEVs compared to normotensive controls were founnd. MgSO treatment further diminished sEVs uptake. ConclusionsPlasma, rather than sEVs, appears to drive BBB disruption in eclampsia. MgSO may influence these effects by reducing sEVs uptake and altering their protein cargo.

physiology↗

bioRxiv2024

hsa-miR-9-5p highly expressed in syncytiotrophoblast-derived extracellular vesicles from early-onset preeclampsia impairs cerebral microvascular endothelial cell pro-angiogenic capacity

BackgroundCerebrovascular complications are the leading cause of maternal mortality associated with preeclampsia. Extracellular vesicles (EVs) containing microRNAs (miRNAs) and derived from syncytiotrophoblast (STB-EVs) are suspected to play a role in these complications. Previously, we found that STB-EVs from the placentas of women with preeclampsia have a higher content of the angiogenesis regulator hsa-miR-9-5p. We now investigate the effects of hsa-miR-9-5p on the proangiogenic properties of brain endothelial cells and identify potential protein targets involved in these processes. MethodsBrain endothelial cells (hCMEC/D3) were treated with hsa-miR-9-5p (0, 5 and 10 nM) to assess cell viability and proliferation. Additionally, cell migration and proteomic profile in hCMEC/D3 treated with hsa-miR-9-5p (10 nM) were also analyzed. ResultsCompared to control, hsa-miR-9-5p significantly reduced hCMEC/D3 cell proliferation and migration without affecting cell viability. Proteomic analysis identified several vital proteins potentially mediating these effects, including vascular endothelial growth factor type C (VEGFC), placental growth factor (PLGF or PGF), and platelet-derived growth factor B (PDGFB). Treatment with hsa-miR-9-5p did not impair the capacity of hCMEC/D3 to respond to tumour necrosis factor- (TNF-). Conclusionhsa-miR-9-5p reduces hCMEC/D3 cell proliferation and migration, and modulates the expression of angiogenic regulators such as VEGFC, PLGF, and PDGFB, without affecting TNF- mediated activation of hCMEC/D3. This suggests that STB-EVs cargo hsa-miR-9-5p may selectively inhibit the proangiogenic capacity of brain endothelial cells. These findings enhance our understanding of cerebrovascular alterations in preeclampsia and may guide future studies and therapeutic interventions.

physiology↗

bioRxiv2024

Extracellular vesicles from preeclampsia disrupt the blood-brain barrier via reduced claudin-5: potential role of vascular endothelial growth factor

BackgroundPhysiopathology of life-treating cerebrovascular complications in preeclampsia are yet unknown. We investigated whether disruption of the blood-brain barrier (BBB), generated using circulating small extracellular vesicles (sEVs) from women with preeclampsia or placentae cultured under hypoxic conditions, impairs the expression of tight junction proteins, such as claudin 5 (CLDN5), mediated by VEGF and activation of VEGF receptor 2 (KDR). MethodssEVs were isolated from plasma (normal pregnancy, sEVs-NP, n=9); preeclampsia, sEVs-PE, n=9) or placental explants from normotensive pregnancies, cultured in normoxia (sEVs-Nor, n=10) or hypoxia (sEVs-Hyp, n=10). The integrity of the BBB was evaluated using in vitro (human and mice brain endothelial cell lines) and in vivo (non-pregnant C57BL/6 mice (4 to 5 months old, (n=10) were injected with sEVs-Hyp), models. ResultssEVs-PE and sEVs-Hyp reduced CLND5 levels (p<0.05) in the endothelial cell membrane without affecting other tight junction proteins. These results were negated with sEVs-PE sonication. sEVs-Hyp injected into non-pregnant mice generated neurological deficits and BBB disruption, specifically in the posterior area of the brain, associated with reduction in CLND5 levels in the brain cortex. Furthermore, sEVs-PE and sEVs-sHyp had higher VEGF levels than sEVs-NP and sEVs-Nor, respectively. Human brain endothelial cells exposed to sEVs-PE or sEVs-sHyp exhibited a reduction in the activation of KDR. ConclusionsEVs from hypoxic placentae and plasma from women with preeclampsia disrupt the BBB, via reduction of CLDN5, a phenomenon that may involve VEGF contained within these vesicles. These findings will improve the elucidation of cerebrovascular alterations in women with preeclampsia.

physiology↗

bioRxiv2022

Reducing the foreign body response on human cochlear implants and their materials in vivo with photografted zwitterionic hydrogel coatings

The foreign body response to implanted materials often complicates the functionality of sensitive biomedical devices. For cochlear implants, this response can reduce device performance, battery life and preservation of residual acoustic hearing. As a permanent and passive solution to the foreign body response, this work investigates ultra-low-fouling poly(carboxybetaine methacrylate) (pCBMA) thin film hydrogels that are simultaneously photo-grafted and photo-polymerized onto polydimethylsiloxane (PDMS). The cellular anti-fouling properties of these coatings are robustly maintained even after six-months subcutaneous incubation and over a broad range of cross-linker compositions. On pCBMA-coated PDMS sheets implanted subcutaneously, capsule thickness and inflammation are reduced significantly in comparison to uncoated PDMS or coatings of polymerized poly(ethylene glycol dimethacrylate) (pPEGDMA) or poly(hydroxyethyl methacrylate) (pHEMA). Further, capsule thickness is reduced over a wide range of pCBMA cross-linker compositions. On cochlear implant electrode arrays implanted subcutaneously for one year, the coating bridges over the exposed platinum electrodes and dramatically reduces the capsule thickness over the entire implant. Coated cochlear implant electrode arrays could therefore lead to persistent improved performance and reduced risk of residual hearing loss. More generally, the in vivo anti-fibrotic properties of pCBMA coatings also demonstrate potential to mitigate the fibrotic response on a variety of sensing/stimulating implants. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=75 SRC="FIGDIR/small/518125v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1d92121org.highwire.dtl.DTLVardef@e2ca3org.highwire.dtl.DTLVardef@948783org.highwire.dtl.DTLVardef@14ce647_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗