Journal of Vascular Research最新文献

Introduction: Exploring the association between oxidative balance score (OBS) and all-cause mortality in hypertension (HTN).

Methods: Data for HTN patients from 2007 to 2018 were extracted from the National Health and Nutrition Examination Survey (NHANES). OBS offers a thorough evaluation of an individual's redox status, with higher score indicates favorable oxidative homeostasis. All-cause mortality was obtained by linkage to National Death Index records through 31 December 2019. Weighted multivariable Cox regression models, Kaplan-Meier curves, receiver operator characteristic (ROC) curve, and random survival forests (RSF) analysis were applied to examine the relationship between OBS and all-cause mortality in HTN.

Results: The cohort included 13,130 participants, with 2,132 deaths. Higher OBS was associated with lower all-cause mortality risk (HR=0.77, 95%CI: 0.65-0.91) in HTN. The relationship also existed in subgroups of male, having/haven't chronic kidney disease, and having cardiovascular disease. Kaplan-Meier curves suggested that participants with higher OBS had superior survival rates compared to those with lower intake. The RSF showed a better survival predictive role for physical activity among the components of OBS.

Conclusion: Higher OBS was related to lower odds of all-cause mortality in patients with HTN. Adopting a healthy lifestyle and consuming an antioxidant-rich diet may improve the prognosis of patients with HTN.

Introduction: The pathogenic role of nitric oxide (NO) signaling during development of thoracic aortic aneurysm (TAA) in Marfan syndrome (MFS) is currently unclear. We characterized vasomotor function and its relationship to the activity of the NO-generating enzymes in mice with early onset progressively severe MFS.

Methods: Wire myography, immunoblotting, measurements of aortic NO and superoxide levels were used to compare vasomotor function, contractile-protein levels, and the activity of endothelial and inducible NO synthase (eNOS and iNOS, respectively) in ascending thoracic aortas of Fbn1mgR/mgR mice relative to wild type (WT) littermates.

Results: Isometric force measurements of aortic rings from 16-day-old male Fbn1mgR/mgR mice revealed a significant reduction in acetylcholine (ACh)-induced relaxation and increased phenylephrine (PE)-promoted contractility, associated with abnormally low eNOSSer1177 phosphorylation, decreased NO production and augmented superoxide levels. Greater aortic contractility was associated with α1-adrenoceptor upregulation and normal levels of contractile proteins. While iNOS inhibition had no effect on vasomotor functions, mutant aortic rings pre-incubated with a non-specific NOS inhibitor yielded a greater PE response, implying a significant contribution of endothelial dysfunction to aortic hypercontractility.

Conclusion: Impaired eNOS signaling disrupts aortic cholinergic relaxation and adrenergic contraction in MFS mice with dissecting TAA.

Introduction Control of blood pressure following acute type B aortic dissection usually requires sympatholytic antihypertensive medication. Although sympathetic nerve activity is central to blood pressure control, its role in the hypertensive response to acute aortic dissection has not been assessed. Methods A prospective pilot study was performed over an 18-month period. Patients presenting with acute type B aortic dissection, confirmed on computed tomographic angiography were recruited. We measured blood pressure, heart rate, muscle sympathetic nerve activity (MSNA) and plasma catecholamine levels in patients following acute type B dissection and controls. Comparisons between groups were made one week (acute phase) and three months after dissection (recovery phase). Results Five patients and four controls were recruited in the study. MSNA was higher in patients than controls during the acute phase of aortic dissection:62 (60 - 62) versus 46 (29 - 60) bursts/min (effect size 0.88) and 88 (54 - 96) versus 71 (44 - 101) bursts/100 beats (effect size 0.60). Plasma normetanephrines were also increased acutely: 821.0 (489.0 - 884.0) versus 417.0 (348.5 - 561.5) pmol/L (effect size 0.85). Conclusion Sympathetic nerve activity is increased acutely during the first week after type B aortic dissection, resolving towards control values after three months. Immediate sympatholytic drug treatment is likely to be crucial in order to prevent the acute and chronic complications of this response.

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: The tumor microenvironment is comprised of neoplastic cells and a variety of host cell types. Investigation of cell dynamics within this environment has motivated in vitro and ex vivo biomimetic model development. Our laboratory recently introduced the tumor spheroid-rat mesentery culture model to investigate cancer-induced lymphatic/blood vessel remodeling. To validate the physiological relevance of this model, the objective of this study was to determine the effect of tumor spheroids on microvascular remodeling after transplantation onto rat mesenteric tissues in vivo.

Methods: Spheroids derived from H1299 lung cancer cells were seeded onto rat mesenteric tissues during a survival surgical procedure. Tissues were harvested 3-5 days post-seeding and stained with PECAM and LYVE-1 to identify blood and lymphatic vessels, respectively.

Results: At all timepoints, cancer cells remained adhered to the tissue. Tissues seeded with tumor spheroids were shown to have increased vascular density, capillary sprouting, and tortuosity compared to sham tissues exposed to sterile saline only. Tumor spheroids also induced the formation of lymphatic/blood vessel connections and LYVE-1-negative protrusions emerging from lymphatic vessels.

Conclusion: Overall, this study underscores the use of in vivo modeling to aid in the discovery of novel vascular growth dynamics and offers new methodologies for studying tumor-induced remodeling.

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: 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: Neutrophil infiltration is responsible for the neuroinflammation during an ischemic stroke. Here, we explored the role of receptor-interacting protein kinase 3 (RIP3) in neutrophil infiltration during an ischemic stroke.

Methods: The rat middle cerebral artery occlusion (MCAO) model was utilized to identify pivotal proteins involved in neutrophil infiltration during an ischemic stroke. Neutrophils were isolated from the peripheral blood of mice, and a co-immunoprecipitation (co-IP) assay was performed to identify the proteins that interact with RIP3.

Results: The rat MCAO model was successfully established. Myeloperoxidase (MPO) was significantly upregulated in the MCAO group, indicating the presence of neutrophil infiltration. RIP3 protein level exhibited a similar trend to MPO protein level, suggesting that neuroinflammation might be partly activated by RIP3 through the promotion of neutrophil infiltration. Co-IP and mass spectrometry analyses suggested that RIP3 facilitated neutrophil infiltration partly by affecting protein kinases (Rock1 and Prkaca) downstream of RIP3, and the interaction between RIP3 and Rock1 or Prkaca was validated by IF and co-IP assays.

Conclusion: In this study, it was observed that RIP3 affects neutrophil infiltration, a critical phenomenon associated with neuronal injury during ischemic stroke, partly by the modulation of downstream proteins such as Rock1 and Prkaca.

Introduction: The dilatory response of healthy retinal arterioles to flicker-light (FL) provocation appears to be biphasic. The vessel diameter rapidly increases (acute phase) over 5-10 s, then barely increases thereafter (maintenance phase) until FL cessation. This reaction is usually characterised at a single point by two parameters: maximum dilation (MD) relative to baseline diameter (MD, %) and time to MD (RT, s). This paper describes the biphasic reaction of retinal arteries during FL provocation using a bi-linear function.

Methods: Retinal arterioles from 45 adults were examined during flicker provocation. Each individual time course of arterial diameter change during FL provocation was characterised by a bi-linear equation and compared with MD and RT.

Results: Slopes of the acute phase were 0.506%/s, and the maintenance phase was nearly flat (0.012%/s). The mean time at which the reaction changed from acute to maintenance phase was 7.4 s which is significantly different from RT (16.0 s). Mean dilation at this point (2.987%) was significantly different from MD (3.734%), but it was still 80% of MD in less than half of RT.

Conclusion: Bi-linear fitting parameters better characterises the arterial dilatory response than MD and RT. Further stratification of clinical groups using bi-linear fitting may provide insight of the underlying physiology of vessel dilation for different pathologies.

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.