Journal of Vascular Research最新文献

Introduction: We investigated the effects of transfusing blood products close to the expiration date (i.e., ≥35 days packed red blood cells [PRBCs] and >3 days platelets [PLTs]) on vascular patients.

Methods: We retrospectively examined all PRBC and PLT transfusions in patients who underwent vascular procedures without cardiopulmonary bypass in Queensland from 2007 to 2013. Mortality, length of stay (LOS), and blood product quantities were compared in patients transfused exclusively with PRBCs <21 days vs. PRBCs ≥35 days and PLTs ≤3 days vs. PLTs >3 days.

Results: No significant mortality difference was found between patients transfused fresh vs. old PRBCs (26/493 [5.3%] vs. 6/152 [3.9%]; OR 0.75; 95% CI: 0.3-1.9). Patients transfused fresh PRBCs experienced a longer LOS (11 days [IQR: 7-20] vs. 10 days [IQR: 7-15]; 95% CI: -4.8 to -0.24) and more PRBC units (3.9 ± 4.5 units vs. 2.1 ± 1.3 units; 95% CI: -2.3 to -0.9). Among patients transfused PLTs, there were no significant differences in mortality (24/124 [19.4%] vs. 14/78 [17.9%]; OR 1.0; 95% CI: 0.5-2.3) between patients transfused fresh vs. old PLTs.

Conclusion: Within the limitations of the retrospective study design, transfusion of older PRBCs or PLTs was associated with fewer transfused units, shorter hospital stays, but no difference in mortality.

Background: The high incidence of vascular and lymphatic metastasis is closely associated with poor prognosis and mortality in cancer. Finding effective inhibitors to prevent pathological angiogenesis and lymphangiogenesis relies on appropriate in vivo models. The chick embryo chorioallantoic membrane (CAM) is formed by the fusion of the chorion and allantois during embryonic development.

Summary: In this context, we primarily summarize the changes in vascular and lymphatic vessel formation in tumors under the action of drugs using this model, providing a preclinical model basis for effective tumor inhibitors.

Key messages: Due to natural immunological defects, chick embryos accept various tissue and species transplants without immune response. The CAM model has been widely used in studying angiogenesis, antiangiogenesis, tumor growth, tumor metastasis, and drug efficacy. This review describes the use of CAM assays as a valuable method for testing the in vivo effects of drugs on vascular and lymphatic vessel formation before further investigating the effects of drugs on tumor vessels and lymphatic vessels in animal models.

Background: The high incidence of vascular and lymphatic metastasis is closely associated with poor prognosis and mortality in cancer. Finding effective inhibitors to prevent pathological angiogenesis and lymphangiogenesis relies on appropriate in vivo models. The chick embryo chorioallantoic membrane (CAM) is formed by the fusion of the chorion and allantois during embryonic development.

Summary: In this context, we primarily summarize the changes in vascular and lymphatic vessel formation in tumors under the action of drugs using this model, providing a preclinical model basis for effective tumor inhibitors.

Key messages: Due to natural immunological defects, chick embryos accept various tissue and species transplants without immune response. The CAM model has been widely used in studying angiogenesis, antiangiogenesis, tumor growth, tumor metastasis, and drug efficacy. This review describes the use of CAM assays as a valuable method for testing the in vivo effects of drugs on vascular and lymphatic vessel formation before further investigating the effects of drugs on tumor vessels and lymphatic vessels in animal models.

Introduction: Previous work indicates that AKAP12 is expressed in endothelial cells as two variants and may play a role in cell motility. However, the role of each variant in cell motility is unknown; therefore, this study investigated the role of AKAP12 in endothelial cell motility with a specific focus on AKAP12 variants, AKAP12v1 and AKAP12v2.

Methods: AKAP12 expression levels in cultured endothelial cells were determined by Western blotting and immunofluorescence microscopy. AKAP12 knockdown and AKAP12 variant knockout were done using antisense oligonucleotide and siRNA treatment and CRISPR/Cas9 knockout, respectively. The effect of AKAP12 variant knockout was further analyzed by RNA-seq.

Results: AKAP12 expression was cell density-dependent, with the highest expression in subconfluent cultures and lowest in confluent cultures. AKAP12 expression was also elevated in cells at the wound edge of wounded endothelial cell monolayers. Knockdown of both variants inhibited cell migration, but CRISPR/Cas9 knockout of AKAP12v1 enhanced migration. RNA-seq revealed that loss of AKAP12v1 affected genes associated with cell migration and intercellular junctions.

Conclusion: We propose that AKAP12v1 and AKAP12v2 play distinct yet complementary roles in endothelial cell migration and likely work together in controlling the signaling events associated with vascular repair and development.

Introduction: The aims of this study were to determine (1) whether endothelial nitric oxide synthase (eNOS) inhibition stimulates endothelial microvesicles (EMVs) release and (2) the effect of EMVs derived from eNOS-inhibited cells on endothelial cell eNOS, inflammation, apoptosis, and tissue-type plasminogen activator (t-PA).

Methods: Human umbilical vein endothelial cells (HUVECs) were treated with the eNOS inhibitor (NG-nitro-l-arginine methyl ester [L-NAME], 300 µM) for 24 h. EMVs from untreated and L-NAME-treated cells were isolated, quantified, and exposed to HUVECs for 24 h.

Results: eNOS-inhibited cells released significantly higher EMVs than untreated cells (81 ± 13 vs. 41 ± 15 EMV/μL; p = 0.005). Expression of total eNOS (97.1 ± 16.4 vs. 157.5 ± 31.2 arbitrary units [AUs]; p = 0.01), p-eNOS (4.9 ± 1.2 vs. 9.1 ± 12.6 AUs; p = 0.02), and NO production (5.0 ± 0.8 vs. 7.0 ± 1.3 µmol/L; p = 0.04) were significantly lower in cells treated with EMVs from L-NAME-treated cells. L-NAME-derived EMVs induced significantly higher IL-6 (38.3 ± 10.3 vs. 21.0 ± 3.8 pg/mL; p = 0.01) and IL-8 (38.9 ± 7.0 vs. 27.2 ± 6.2 pg/mL; p = 0.04) production concurrent with higher expression of p-NF-κB p65 (Ser536) (9.7 ± 1.6 vs. 6.1 ± 1.2 AUs; p = 0.01). Expression of activated caspase-3 was higher (9.5 ± 1.1 vs. 6.4 ± 0.4 AUs) and t-PA lower (24.2 ± 4.3 vs. 36.2 ± 8.4 AUs; p = 0.04) in cells treated with L-NAME-derived EMVs.

Conclusion: eNOS inhibition induces an increase in EMV release and an EMV phenotype with adverse cellular effects.

Introduction: Visualization of the intact microvascular network in skeletal muscle requires labeling the entire network in whole mount preparations where muscle fibre length can be set to near optimal but the tools to do this are not clear.

Methods: We intravascularly injected CD-1 mice with different fluorescently labelled lectins (fluorescent isolectin GS-IB4 [ISO], wheat germ agglutinin [WGA], lycopersicon esculentum [LYCO]) or FITC-labelled gel. Soleus, extensor digitorum longus, diaphragm, gluteus maximus and cremaster muscles were excised, pinned at optimal sarcomere length and viewed using fluorescence microscopy.

Results: WGA and LYCO were effective at labeling the entire vascular network with WGA labeling capillaries more brightly. ISO labelled the arteriolar vasculature and early segments of the capillaries but not the full length of the capillaries or the venular network. FITC-labelled gel was effective at labelling the microvascular network but not all small vessels were consistently labelled. The pattern of staining for each labelling method was similar across all muscle fibre-types tested.

Conclusions: WGA was optimal for perfusion labeling and visualization of the intact microvascular network in whole mount skeletal muscle preparations and can be used in combination with ISO to distinguish the arteriolar and venous sides of the network.

Introduction: Visualization of the intact microvascular network in skeletal muscle requires labeling the entire network in whole mount preparations where muscle fibre length can be set to near optimal but the tools to do this are not clear.

Methods: We intravascularly injected CD-1 mice with different fluorescently labelled lectins (fluorescent isolectin GS-IB4 [ISO], wheat germ agglutinin [WGA], lycopersicon esculentum [LYCO]) or FITC-labelled gel. Soleus, extensor digitorum longus, diaphragm, gluteus maximus and cremaster muscles were excised, pinned at optimal sarcomere length and viewed using fluorescence microscopy.

Results: WGA and LYCO were effective at labeling the entire vascular network with WGA labeling capillaries more brightly. ISO labelled the arteriolar vasculature and early segments of the capillaries but not the full length of the capillaries or the venular network. FITC-labelled gel was effective at labelling the microvascular network but not all small vessels were consistently labelled. The pattern of staining for each labelling method was similar across all muscle fibre-types tested.

Conclusions: WGA was optimal for perfusion labeling and visualization of the intact microvascular network in whole mount skeletal muscle preparations and can be used in combination with ISO to distinguish the arteriolar and venous sides of the network.

Introduction: Peripheral artery disease (PAD) affects over 200 million people globally and remains a therapeutic challenge, particularly in patients who are not candidates for standard revascularization. While shear stress-induced angiogenesis holds promise as a novel therapeutic strategy, translational platforms to evaluate its efficacy are lacking.

Methods: We developed a large-animal model of PAD using familial hypercholesterolemic miniature swine fed an atherogenic diet to induce metabolic syndrome. Hindlimb ischemia was surgically induced by excising the right external iliac artery with collateral ligation. After a 3-4 week ischemic phase, targeted retrograde perfusion was delivered via a miniaturized extracorporeal centrifugal pump to generate sustained flow-mediated shear stress. Functional, imaging, and molecular endpoints were assessed throughout the protocol.

Conclusion: This reproducible swine model offers a metabolically relevant platform for investigating perfusion-driven angiogenesis and evaluating novel flow-based revascularization therapies for PAD. It addresses a critical translational gap in preclinical vascular research.

This is the collection of abstracts for the Biennial Meeting of the European Society for Microcirculation (ESM 2025), to be held in Szeged, Hungary between May 19-22, 2025.

Introduction: This study was designed to test the hypothesis that coronary artery adaptations during the postpartum period are related to underlying reductions in endothelium-dependent relaxation and/or augmented smooth muscle vasoconstrictor responsiveness.

Methods: In vivo experiments were performed in control (nonpregnant) and postpartum swine 35-45 days of postdelivery, with isometric tension experiments performed in isolated coronary arteries from those animals.

Results: Coronary artery rings demonstrated increases in active tension generation following incremental increases in passive stretch with no differences between groups. Endothelium-dependent relaxation to bradykinin was attenuated in arteries from postpartum swine versus control (p < 0.005). Concentration-dependent contractions to the thromboxane A2 mimetic U46619 (0.1 nm-1 µm) were shifted rightward (EC50 27 ± 10 nm vs. 238 ± 66 nm; p < 0.01) in arteries from postpartum swine, with no changes in maximum contractile responses (p = 0.68). Intracoronary administration of U46619 (1 nm-1 µm) in open-chest swine decreased coronary blood flow ∼45 ± 3% in nonpregnant controls but had no effect on coronary blood flow in postpartum swine. Concentration-dependent contractions to KCl (5-90 mm) showed a rightward shift in arteries from postpartum swine (15.6 ± 1.4 mm vs. 21.8 ± 1.9 mm; p = 0.03), with no change in maximum response. Taken together, the postpartum period is associated with reduced endothelium-dependent relaxation and responsiveness to receptor-dependent and -independent vasoconstrictor stimuli.

Conclusion: These findings indicate that chronic exposure of the coronary circulation to the pregnancy/postpartum milieu results in functional adaptations in sensitivity to paracrine/hormonal compounds that should be further explored.

Introduction: Lymphatic vessels and lymph nodes (LNs) are part of the lymphatic system taking care of interstitial tissue homoeostasis, lipid transport, and immune response. The interposition of LNs in between the lymphatic vasculature allows the filtration of lymph fluid, cell-cell interactions, and also the transfer of lymph fluid into the venous system. An important role of lymphatic flow, which is often underestimated, is the active involvement of lymph flow and the lymphatic vasculature in immunologic function.

Summary: The present review summarizes the current knowledge of the different functional units of the lymphatic transport system trying to create a model of their interplay and options to react to inflammatory conditions. Remodelling of the lymphatic system during inflammation includes lymphangiogenesis, changed fluid transport rates, and modification of LN morphology. Alterations of these processes can aggravate inflammatory processes, leading to an incomplete resolution of the inflammation and often ending in chronic inflammatory condition. Despite the development of histological markers to visualize lymphatic vessels, new imaging methods and increased knowledge about the different parts of the lymphatic system the general overview about the interplay of the different components is missing.

Key messages: We show the importance of lymphatic flow in the initiation of the immune response and the solution of an inflammation. We speculate that the increase in density and vessel diameter of lymph vessels is necessary to increase the fluid influx, efflux and the migration of cells into the LN. A failure of antigen-tissue clearance leads to chronic inflammation. Remodelling of LN morphology and vasculature is also necessary in this reaction. An overrun of the defending capacity of the LN is prevented by the immune system via control of the lymph vessel transport capacity and LN remodelling.