Microvascular research最新文献

Background

Arterial baroreflex dysfunction, like many other central nervous system disorders, involves disruption of the blood-brain barrier, but what causes such disruption in ABR dysfunction is unclear. Here we explored the potential role of platelets in this disruption.

Methods

ABR dysfunction was induced in rats using sinoaortic denervation, and the effects on integrity of the blood-brain barrier were explored based on leakage of Evans blue or FITC-dextran, while the effects on expression of CD40L in platelets and of key proteins in microvascular endothelial cells were explored using immunohistochemistry, western blotting and enzyme-linked immunosorbent assay. Similar experiments were carried out in rat brain microvascular endothelial cell line, which we exposed to platelets taken from rats with ABR dysfunction.

Results

Sinoaortic denervation permeabilized the blood-brain barrier and downregulated zonula occludens-1 and occludin in rat brain, while upregulating expression of CD40L on the surface of platelets and stimulating platelet aggregation. Similar effects of permeabilization and downregulation were observed in healthy rats that received platelets from animals with ABR dysfunction, and in rat brain microvascular endothelial cells, but only in the presence of lipopolysaccharide. These effects were associated with activation of NF-κB signaling and upregulation of matrix metalloprotease-9. These effects of platelets from animals with ABR dysfunction were partially blocked by neutralizing antibody against CD40L or the platelet inhibitor clopidogrel.

Conclusion

During ABR dysfunction, platelets may disrupt the blood-brain barrier when CD40L on their surface activates NF-kB signaling within cerebral microvascular endothelial cells, leading to upregulation of matrix metalloprotease-9. Our findings imply that targeting CD40L may be effective against cerebral diseases involving ABR dysfunction.

Changes in the structure and function of nailfold capillaries may be indicators of numerous diseases. Noninvasive diagnostic tools are commonly used for the extraction of morphological information from segmented nailfold capillaries to study physiological and pathological changes therein. However, current segmentation methods for nailfold capillaries cannot accurately separate capillaries from the background, resulting in issues such as unclear segmentation boundaries. Therefore, improving the accuracy of nailfold capillary segmentation is necessary to facilitate more efficient clinical diagnosis and research. Herein, we propose a nailfold capillary image segmentation method based on a U²-Net backbone network combined with a Transformer structure. This method integrates the U²-Net and Transformer networks to establish a decoder–encoder network, which inserts Transformer layers into the nested two-layer U-shaped architecture of the U²-Net. This structure effectively extracts multiscale features within stages and aggregates multilevel features across stages to generate high-resolution feature maps. The experimental results demonstrate an overall accuracy of 98.23 %, a Dice coefficient of 88.56 %, and an IoU of 80.41 % compared to the ground truth. Furthermore, our proposed method improves the overall accuracy by approximately 2 %, 3 %, and 5 % compared to the original U²-Net, Res-Unet, and U-Net, respectively. These results indicate that the Transformer–U²Net network performs well in nailfold capillary image segmentation and provides more detailed and accurate information on the segmented nailfold capillary structure, which may aid clinicians in the more precise diagnosis and treatment of nailfold capillary-related diseases.

In optical imaging, optical clearing agents are commonly used to enhance the structural details of a sample. The current study investigates how to use it to improve the data obtained by an optical coherence tomography angiography system. A natural edible oil with no chemical base has been used for optical clearing. In-vivo testing on mice and humans yielded excellent optical clearing. Using computational techniques, the improvement in angiography signal caused by the optical clearing agent is investigated qualitatively and quantitatively. Compared to the control group, applying the edible oil-based optical clearing agent demonstrated improved vessel percentage and refined vascular signal intensity along depth.

Background

Coronary artery bypass grafting (CABG) is considered the choice treatment for patients suffering from coronary artery disease (CAD). In the inflammatory milieu of cardiopulmonary bypass (CPB), systemic inflammatory response syndrome (SIRS) can induce a platelet pro-inflammatory state which could exacerbate post-CABG inflammatory status while affecting hemostatic function in patients. Therefore, focusing on platelets, the study presented here attempted to evaluate the pro-inflammatory and immunomodulatory profile of platelets as well as pro-aggregatory status during CABG.

Methods

Platelets from patients undergoing CABG were subjected to flowcytometry analysis to evaluate P-selectin and CD40L expressions and PAC-1 binding in five intervals of 24 h before surgery, immediately, 2 h, 24 h, and one week after surgery. Moreover, intra-platelet TGF-β1 was also examined with western blotting.

Results

Data showed increases of P-selectin and CD40L expressions in patients, with the meaningful loss of platelet contents of TGF-β1 after CABG (p < 0.001), where the changes tended to recover by day 7 of surgery while remaining above baseline (p < 0.001). Meanwhile, no significant change in PAC-1 binding capacity was shown.

Conclusion

The study presented here suggests that although the release of pro-inflammatory substances from platelets during CABG supports the post-operative inflammatory state, platelets are not pro-aggregatory enough to enhance thrombotic events after surgery. Whilst these observations could be due to successful medical interventions to optimize hemostasis during and after surgery, post-CABG reversal of anticoagulant by protamine is considered as another factor that may also have contributed to preventing pro-aggregatory but not pro-inflammatory and immunomodulatory functions of platelets.

Purpose

To determine the changes in retinal microvascular density after a 24-week high-speed circuit resistance training program (HSCT) in healthy older adults.

Methods

Thirty healthy older adults were recruited and randomly assigned to either a training group (HSCT) or a non-training (CON) group. Fifteen subjects (age 73.3 ± 7.76 yrs) in the HSCT group exercised three times per week on non-consecutive days for 24 weeks. Fifteen subjects in the CON group (age 72.2 ± 6.04 yrs) did not have formal physical training. Both eyes of each subject were imaged using optical coherence tomography angiography (OCTA) at baseline and at the 24-week follow-up. The vessel densities of the retinal vascular network (RVN), superficial vascular plexus (SVP), and deep vascular plexus (DVP) were measured.

Results

There were no demographic differences between the study groups. There were significant decreases in the retinal vessel densities of RVN, SVP and DVP in the HSCT group (P < 0.05). However, there were no significant changes in all three vascular measurements in the CON group (P > 0.05), although the changes showed a decreasing trend. The decreased vessel densities were doubled in the HSCT group in comparison to the CON group. However, the differences between groups did not reach a significant level (P > 0.05).

Conclusions

This is the first study to reveal the decreased retinal vessel densities as a possible imaging marker for the beneficial effects of the 24-week HSCT program in older adults.

Extracellular signal-regulated kinase (Erk)-5 is a key mediator of endothelial cell homeostasis, and its inhibition causes loss of critical endothelial markers leading to endothelial dysfunction (ED). Circulating oxidized low-density lipoprotein (oxLDL) has been identified as an underlying cause of ED and atherosclerosis in metabolic disorders. Silymarin (Sym), a flavonolignan, possesses various pharmacological activities however its preventive mechanism in ED warrants further investigation. Here, we have examined the effects of Sym in regulating the expression of Erk-5 and ameliorating ED using in vitro and in vivo models. Primary human umbilical vein endothelial cells (pHUVECs) viability was measured by MTT assay; mRNA and protein expression by RT-qPCR and Western blotting; tube-formation assay was performed to examine endothelialness. In in-vivo experiments, normal chow-fed mice (control) or high-fat diet (HFD)-fed mice were administered Sym or Erk-5 inhibitor (BIX02189) and body weight, blood glucose, plasma-LDL, oxLDL levels, and expression of EC markers in the aorta were examined. Sym (5 μg/ml) maintained the viability and tube-formation ability of oxLDL exposed pHUVECs. Sym increased the expression of Erk-5, vWF, and eNOS and decreased ICAM-1 at transcription and translation levels in oxLDL-exposed pHUVECs. In HFD-fed mice, Sym reduced the body weight, blood glucose, LDL-cholesterol, and oxLDL levels, and increased the levels of vWF and eNOS along with Erk-5 and decreased the level of ICAM-1 in the aorta. These data suggest that Sym could be a potent anti-atherosclerotic agent that could elevate Erk-5 level in the ECs and prevent ED caused by oxidized LDL during HFD-induced obesity in mice.

Objectives

Laser Doppler Flowmetry (LDF) is a non-invasive technique for the assessment of tissue blood flow, but increased reproducibility would facilitate longitudinal studies. The aim of the study was to assess the interday reproducibility of Laser Doppler Flowmetry (LDF) at rest, at elevated local temperatures, and with the use of the vasodilator Methyl Nicotinate (MN) in six interconnected protocols for the measurement of the blood supply to the microvascular bed of the gingiva.

Methods

Ten healthy volunteers were included. Interweek LDF measurements with custom-made acrylic splints were performed. Six protocols were applied in separate regions of interest (ROI): 1; basal LDF, 2; LDF with thermoprobe 42 °C, 3; LDF with thermoprobe 45 °C, 4; LDF with thermoprobe 42 °C and MN, 5; LDF with thermoprobe 45 °C and MN and 6; LDF with MN.

Results

Intra-individual reproducibility was assessed by the within-subject coefficient of variation (wCV) and the intraclass correlation coefficient (ICC). Basal LDF measurements demonstrated high reproducibility with wCV 11.1 in 2 min and 10.3 in 5 min. ICC was 0.9 and 0.92. wCV after heat and MN was 4.9–10.3 and ICC 0.82–0.93. The topically applied MN yielded increased blood flow.

Conclusion

This is the first study evaluating the reproducibility of basal LDF compared to single or multiple vasodilatory stimuli in gingiva. Multiple collector fibers probe and stabilizing acrylic splints are recommended. Vasodilatory stimulation showed a tendency toward higher reproducibility. Furthermore, MN yields vasodilation in gingiva.