Microvascular research最新文献

Introduction

Laser doppler flowmetry (LDF) allows non-invasive assessment of microvascular functions. The combination of LDF with an occlusion functional test enables study of post-occlusive reactive hyperemia (PORH), providing additional information about vasomotor function, capillary blood flow reserve, and the overall reactivity of the microvascular system.

Aim

To identify early alterations of PORH variables in the skin of a rat in hemorrhagic shock (HS).

Material and methods

Male Wistar rats (n = 14) weighing 400–450 g were anesthetized with a combination of tiletamine/zolazepam (20 mg/kg) and xylazine (5 mg/kg). The animals breathed on their own, and were placed on a heated platform in the supine position. A PE-50 catheter was inserted into the carotid artery to measure the mean arterial pressure (MAP). The optical probe of the Laser Doppler device was installed on the plantar surface of the hind limb of a rat; a pneumatic cuff was applied proximal to the same limb. The occlusion time was 3 min. The following physiological variables were measured at baseline and 30 min after blood loss: MAP, mmHg; mean cutaneous blood flow (M, PU); cutaneous vascular conductance (CVC = M/MAP); peak hyperemia (M_max, PU) and maximum cutaneous vascular conductance (CVC_max) during PORH. In the HS group (n = 7), 30 % of the estimated blood volume was taken within 5 min. There was no blood loss in the group of sham-operated animals (Sham, n = 7). The results are presented as Me [25 %;75 %]. The U-Mann-Whitney criterion was used to evaluate intergroup differences. Differences were considered statistically significant at p < 0.05.

Results

The groups did not differ at baseline. Blood loss led to a significant decrease in MAP (43 [31;46] vs. 94 [84;104] mmHg), M (11.5 [16.9;7.8] vs 16.7 [20.2;13.9]) and M_max (18.1 [16.4;21.8] vs. 25.0 [23.0;26.2]) in the HS group compared to the Sham group, respectively. At the same time, both CVC (0.25 [0.23;0.30] vs. 0.16 [0.14;0.21]) and CVC_max (0.55 [0.38;0.49] vs 0.24 [0.23; 0.29]) increased after blood loss in the HS group compared to the Sham group. Arterial blood gas analysis revealed metabolic lactic acidosis in the HS group.

Conclusion

In this rat model of HS, alterations in cutaneous blood flow are manifested by a decrease in perfusion (M) and the intensity of PORH (M_max) with a simultaneous increase in vascular conductance (CVC and CVC_max).

Background

Renal Resistive Index (RRI) is an important and non-invasive parameter of renal damage and it is associated with abnormal microcirculation or to a parenchymal injury. The aim of our study was to compare the RRI in a cohort of patients with renal diseases categorized in three groups: nephrotic syndrome (NS), acute nephritic syndrome (ANS) and patients with urinary abnormalities (UA).

Methods

Four hundred eighty-two patients with median age of 48 years (IQR 34–62) with indications for kidney disease were included in the study. Biochemical analyses, clinical assessment with detection of NS, ANS and UA and comorbidities were reported. Renal Doppler ultrasound with RRI was evaluated in all patients at the time of enrolment.

Results

NS was present in 81 (16.8 %) patients while ANS in 81 (16.8 %) and UA in 228 (47.3 %) patients. Patients with ANS showed significant higher RRI compared to both patients with NS [0.71 (IQR 0.67–0.78) vs 0.68 (0.63–0.73), p < 0.001] and UA [0.71 (0.67–0.78) vs 0.65 (0.61–0.71), p < 0.001]; RRI was higher in NS patients than in patients with UA [0.68 (0.63–0.73) vs 0.65 (0.61–0.71), p < 0.001]. Patients with ANS had significantly lower median estimated glomerular filtration rate (eGFR) compared respectively to NS and UA patients [19.7 ml/min vs 54.8 ml/min and vs 72.3 ml/min, p < 0.001], while renal length was significantly higher in patients with NS compared to both patients with ANS and UA [111.88 mm vs 101.98 mm and vs 106.15, p < 0.001]. Patients with ANS had more frequently hematuria and RRI ≥ 0.70 (p < 0.001) compared to both patients with NS and patients with UA. The multiple regression analysis, weighted for age, showed that RRI inversely correlates with eGFR (β coefficient = −0.430, p < 0.001).

Conclusions

Higher and pathological RRI were found in ANS than NS and UA. Renal resistive index in ANS reflects changes in intrarenal perfusion and microvascular dysfunction related to disease characteristics.

Objective

This research was dedicated to investigating the impact of the SNHG12/microRNA (miR)-15b-5p/MYLK axis on the modulation of vascular smooth muscle cell (VSMC) phenotype and the formation of intracranial aneurysm (IA).

Methods

SNHG12, miR-15b-5p and MYLK expression in IA tissue samples from IA patients were tested by RT-qPCR and western blot. Human aortic vascular smooth muscle cells (VSMCs) were cultivated with H₂O₂ to mimic IA-like conditions in vitro, and the cell proliferation and apoptosis were measured by MTT assay and Annexin V/PI staining. IA mouse models were established by induction with systemic hypertension combined with elastase injection. The blood pressure in the tail artery of mice in each group was assessed and the pathological changes in arterial tissues were observed by HE staining and TUNEL staining. The expression of TNF-α and IL-1β, MCP-1, iNOS, caspase-3, and caspase-9 in the arterial tissues were tested by RT-qPCR and ELISA. The relationship among SNHG12, miR-15b-5p and MYLK was verified by bioinformatics, RIP, RNA pull-down, and luciferase reporter assays.

Results

The expression levels of MYLK and SNHG12 were down-regulated and that of miR-15b-5p was up-regulated in IA tissues and H₂O₂-treated human aortic VSMCs. Overexpressed MYLK or SNHG12 mitigated the decrease in proliferation and increase in apoptosis of VSMCs caused by H₂O₂ induction, and overexpression of miR-15b-5p exacerbated the decrease in proliferation and increase in apoptosis of VSMCs caused by H₂O₂ induction. Overexpression of miR-15b-5p reversed the H₂O₂-treated VSMC phenotypic changes caused by SNHG12 up-regulation, and overexpression of MYLK reversed the H₂O₂-treated VSMC phenotypic changes caused by up-regulation of miR-15b-5p. Overexpression of SNHG12 reduced blood pressure and ameliorated arterial histopathological damage and VSMC apoptosis in IA mice. The mechanical analysis uncovered that SNHG12 acted as an endogenous RNA that competed with miR-15b-5p, thus modulating the suppression of its endogenous target, MYLK.

Conclusion

Decreased expression of SNHG12 in IA may contribute to the increasing VSMC apoptosis via increasing miR-15b-5p expression and subsequently decreasing MYLK expression. These findings provide potential new strategies for the clinical treatment of IA.

Filariasis is a chronic disease where parasitic worms survive in human hosts even for decades and lead to complications like lymphedema and elephantiasis. Despite the persistent existence of filarial parasites in human hosts, fatal and thrombotic complications are not known, unlike other parasitic diseases like malaria. This suggests that filarial parasites might be affecting the host's platelet functions. This study was conducted to examine platelet functions in confirmed filariasis patients and healthy controls. Results showed that filariasis patients had larger platelets, inhibited aggregation, and slower speed of aggregation, compared to controls. However, in vivo markers of platelet activation and degranulation (beta thromboglobulin and soluble P-selectin) were not affected. Observations suggested that there is increased platelet turnover, cellular apoptosis and inhibited platelet functions in filariasis patients compared to controls. Platelet function inhibition was not associated with the duration of disease, lymphedema-affected organs, or gender of patients. This study confirms that filarial parasites modulate platelet functions in human hosts.

The complexity of microvascular circulation has led to the development of advanced imaging techniques and biomimetic models. This study developed a multifaceted microfluidic-based microdevice as an in vitro model of microvasculature to replicate important geometric and functional features of in vivo perfusion in mice. The microfluidic device consisted of a microchannel for blood perfusion, mirroring the natural hierarchical branching vascular structures found in mice. Additionally, the device incorporated a steady gradient of oxygen (O₂) which diffused through the polydimethylsiloxane (PDMS) layer, allowing for dynamic blood oxygenation. The assembled multi-layered microdevice was accompanied by a dual-modal imaging system that combined laser speckle contrast imaging (LSCI) and intrinsic signal optical imaging (ISOI) to visualize full-field blood flow distributions and blood O₂ profiles. By closely reproducing in vivo blood perfusion and oxygenation conditions, this microvasculature model, in conjunction with numerical simulation results, can provide quantitative information on physiologically relevant hemodynamics and key O₂ transport parameters that are not directly measurable in traditional animal studies.

Objective

Ischemia/reperfusion can impair microcirculatory blood flow. It remains unknown whether colloids are superior to crystalloids for restoration of microcirculatory blood flow during ischemia/reperfusion injury. We tested the hypothesis that goal-directed colloid – compared to crystalloid – therapy improves small intestinal, renal, and hepatic microcirculatory blood flow in pigs with ischemia/reperfusion injury.

Methods

This was a randomized trial in 32 pigs. We induced ischemia/reperfusion by supra-celiac aortic-cross-clamping. Pigs were randomized to receive either goal-directed isooncotic hydroxyethyl-starch colloid or balanced isotonic crystalloid therapy. Microcirculatory blood flow was measured using Laser-Speckle-Contrast-Imaging. The primary outcome was small intestinal, renal, and hepatic microcirculatory blood flow 4.5 h after ischemia/reperfusion. Secondary outcomes included small intestinal, renal, and hepatic histopathological damage, macrohemodynamic and metabolic variables, as well as specific biomarkers of tissue injury, renal, and hepatic function and injury, and endothelial barrier function.

Results

Small intestinal microcirculatory blood flow was higher in pigs assigned to isooncotic hydroxyethyl-starch colloid therapy than in pigs assigned to balanced isotonic crystalloid therapy (768.7 (677.2–860.1) vs. 595.6 (496.3–694.8) arbitrary units, p = .007). There were no important differences in renal (509.7 (427.2–592.1) vs. 442.1 (361.2–523.0) arbitrary units, p = .286) and hepatic (604.7 (507.7–701.8) vs. 548.7 (444.0–653.3) arbitrary units, p = .376) microcirculatory blood flow between groups. Pigs assigned to colloid – compared to crystalloid – therapy also had less small intestinal, but not renal and hepatic, histopathological damage.

Conclusions

Goal-directed isooncotic hydroxyethyl-starch colloid – compared to balanced isotonic crystalloid – therapy improved small intestinal, but not renal and hepatic, microcirculatory blood flow in pigs with ischemia/reperfusion injury. Whether colloid therapy improves small intestinal microcirculatory blood flow in patients with ischemia/reperfusion needs to be investigated in clinical trials.

Purpose

The aim of this study was to assess the impact of acute, heavy alcohol consumption on the ocular microvasculature, providing insight into the largely unexplored response of microvascular structures to excessive drinking.

Methods

Healthy volunteers in this prospective pilot study were tasked with consuming spirits, wine, and water at different times. Alcohol intake was measured according to body weight (g/kg). The ocular microvascular parameters primarily including choroidal volume (CV) and choroidal vessel volume (CVV) reflecting arteriolovenularity, and choroidal capillary density (CCD) reflecting capillary, were evaluated using swept-source optical coherence tomography angiography at baseline and 0.5-, 1-, 2-, and 3-hour post-consumption.

Results

A total of 34 eyes underwent 170 successful examinations in this study. After consuming spirits or wine, we observed significant decreases in CV and CVV values (all P < 0.01 for 0.5-, 1-, 2-, and 3-hour post-consumption), along with significant increase in CCD (P < 0.05 at 0.5-, 1-, 2-hour post-spirits consumption and 1-hour post-wine consumption). The most pronounced changes occurred 1-hour after spirits or wine consumption (all P < 0.001 in both univariate and multivariate model). However, post-consumption changes in the ocular microvasculature showed no significant differences between spirits and wine (P > 0.05). Additionally, no significant differences were observed in any parameters after water intake (all P > 0.05).

Conclusions

Excessive alcohol consumption leads to ocular arteriolovenular vasoconstriction and capillary vasodilation, most evident 1-hour post-consumption of spirits and wine. Our research provides insight into alcohol's immediate ocular microvascular effects, hinting at systemic microvascular effects.

Purpose

The aim of this study was to investigate the microvascular changes in the retina and choroid in gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) and to compare the results with those of healthy pregnant subjects.

Methods

Twenty-nine pregnant subjects with coexisting GDM and PIH (group 1) and 36 healthy pregnant subjects (group 2) were enrolled in the study. All subjects were examined by optical coherence tomography (OCT) and angiography (OCTA). The retina, retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), choroidal thickness (CT), superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC) vascular density (VD), and foveal avascular zone (FAZ) were measured.

Results

We observed that the values of CT and VD were lower in group 1 than in group 2. No significant difference was found between groups in RT, FAZ area and CC VD. SCP and DCP VD values were higher in group 2 in all quadrants. We observed a significant increase in FAZ area and CC VD with increasing systolic blood pressure. No correlation was observed between diastolic blood pressure and FBS with other parameters. In group 1, FAZ area was significantly higher in the diet-treated group than in the insulin-treated group.

Conclusion

Monitoring and treatment of pregnant women with PIH and GDM is important because of the risks that may occur during pregnancy. We believe that changes in microvascular circulation can be detected noninvasively with OCTA, even in the absence of clinical or retinal findings.

Previous studies have shown that expression of the endothelial laminin receptor α6β4 integrin in the brain is uniquely restricted to arterioles. As exposure to chronic mild hypoxia (CMH, 8 % O₂) stimulates robust angiogenic and arteriogenic remodeling responses in the brain, the goal of this study was to determine how CMH influences cerebrovascular expression of the β4 integrin as well as its potential ligands, laminin 411 and 511, containing the α4 and α5 laminin subunits respectively, and then define how aging impacts this expression. We observed the following: (i) CMH launched a robust arteriogenic remodeling response both in the young (10 weeks) and aged (20 months) brain, correlating with an increased number of β4 integrin+ vessels, (ii) while the laminin α4 subunit is expressed evenly across all cerebral blood vessels, laminin α5 was highly expressed preferentially on β4 integrin+ arterioles, (iii) CMH-induced arteriolar remodeling was associated with strong downregulation of the laminin α4 subunit but no change in the laminin α5 subunit, (iv) in addition to its expression on arterioles, β4 integrin was also expressed at lower levels on capillaries specifically in white matter (WM) tracts but not in the grey matter (GM), and (v), these observations were consistent in both the brain and spinal cord, and age had no obvious impact. Taken together, our findings suggest that laminin 511 may be a specific ligand for α6β4 integrin and that dynamic switching of the laminin subunits α4 and α5 might play an instructive role in arteriogenic remodeling. Furthermore, β4 integrin expression differentiates WM from GM capillaries, highlighting a novel and important difference.