Microvascular research最新文献

Purpose

To investigate the impact of exercise and mask-wearing on retinal microvasculature using optical coherence tomography angiography (OCTA).

Methods

A total of 30 healthy volunteers were enrolled and tasked with physical exercise to reach 75–80 % maximum heart rates. Swept-source OCTA was performed on the macular region and optic nerve head (ONH) in participants with no mask, surgical mask, or N95 mask at quiescent conditions (Step 1) and 0 min, 10 min, 20 min, and 30 min post-exercise (Steps 2–5, respectively). The functional vessel density (VD), including the superficial and deep plex (SP and DP) in the macular area and the superficial plex (SP), nerve fiber plex, and small vessels in the optic nerve head, were measured.

Results

Under quiescent conditions, the functional VD of SP and DP exhibited significant reduction with surgical and N95 masks in the foveal area (P < 0.05). In step 2 (immediately after training) with or without masks, functional VD of SP and nerve fiber both showed significant reduction in the inside disc and peripapillary area, small functional VD of nerve fiber in the ONH showed significant reduction in peripapillary area (P < 0.05). These changes had been recovered in Step 5 (30 min post-exercise) in all groups (no-mask, surgical mask and N95 mask groups) (P > 0.05).

Conclusions

Mask-wearing and physical exercise reduce retinal functional VD in macular and ONH areas. The retinal vasoconstriction induced by exercise tends to recover after rest for approximately 30 min. Our research provides insights into mask-wearing and physical exercise's immediate retinal microvasculature effects, hinting at systemic microvascular changes.

Psoriasis is characterized by excessive angiogenesis, with increased distortion and dilation of the dermal blood vessels. These vascular alterations are ascribed, at least in part, to the changes in dermal microvascular endothelial cell functions. However, despite the recognition of vascular normalization as an emerging strategy for the treatment of psoriasis, in-depth studies of human dermal microvascular endothelial cells (HDMECs) have been missing. The difficulty of isolation and culture of HDMECs has impeded the study of endothelial dysfunction in psoriasis. Researchers have done a great deal of work to study the abnormal characteristics of keratinocytes, fibroblasts, and leukocytes in psoriatic skin tissue. Recently, with successful isolation of HDMECs from psoriasis, great progress has been made in the elucidation of the pathogenic role of these cells in psoriasis. It is of great therapeutic significance to study the molecular mechanism of HDMECs in psoriasis. We review here the abnormalities of HDMECs in psoriasis.

Background

Flowmotion analysis of the microcirculatory blood flow is a method to extract information about the vessel regulatory function. It has previously shown promise when applied to measurements during a post-occlusive reactive hyperemia. However, the reperfusion peak and the following monotonic decline introduces false low frequencies that should not be interpreted as rhythmic vasomotion effect.

Aim

To develop and validate a robust method for flowmotion analysis of post-occlusive reactive hyperemia signals.

Method

The occlusion-induced reperfusion response contains a typical rapid increase followed by a monotonic decline to baseline. A mathematical model is proposed to detrend this transient part of the signal to enable further flowmotion analysis. The model is validated in 96 measurements on healthy volunteers.

Results

Applying the proposed model corrects the flowmotion signal without adding any substantial new false flowmotion components.

Conclusion

Future studies should use the proposed method or equivalent when analyzing flowmotion during post-occlusive reactive hyperemia to ensure valid results.

Purpose

To investigate the correlation between morphological lesions and functional indicators in eyes with neovascular age-related macular degeneration (nAMD).

Methods

This was a prospective observational study of treatment-naïve nAMD eyes. Various morphological lesions and impaired retinal structures were manually measured at baseline and month-3 in three-dimensional optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) images, including the volumes (mm³) of macular neovascularization (MNV), avascular subretinal hyperreflective material (avascular SHRM), subretinal fluid (SRF), intraretinal fluid (IRF), serous pigment epithelial detachment (sPED) and the impaired area (mm²) of ellipsoid zone (EZ), external limiting membrane (ELM) and outer nuclear layer (ONL).

Results

Sixty-three eyes were included. The volume of avascular SHRM showed persistent positive associations with the area of EZ damage, both at baseline, month-3, and change values (all P < 0.001). Poor BCVA (month-3) was associated with larger volumes of baseline IRF (β = 0.377, P < 0.001), avascular SHRM (β = 0.306, P = 0.032), and ELM impairment area (β = 0.301, P = 0.036) in multivariate model. EZ and ELM impairment were primarily associated with baseline avascular SHRM (β = 0.374, p = 0.003; β = 0.388, P < 0.001, respectively), while ONL impairment primarily associated with MNV (β = 0.475, P < 0.001).

Conclusion

The utilization of three-dimensional measurements elucidates the intrinsic connections among various lesions and functional outcomes. In particular, avascular SHRM plays an important role in prognosis of nAMD.

Background

Systemic sclerosis (SSc) is a complex autoimmune connective-tissue disease, characterised by vasculopathy and fibrosis of the skin and internal organs. Activation of microvascular endothelial cells (ECs) causes the intimal hyperplasia that characterises the vascular remodelling in SSc. The most frequent complication of SSc is the development of digital ulcers (DUs). Thymic stromal lymphopoietin (TSLP) may trigger fibrosis and sustain vascular damage. Aim of this study was to evaluate the correlation between serum level of TSLP and DUs.

Methods

75 consecutive SSc patients were enrolled and serum TSLP levels were measured. The presence of history of DUs (HDU) was evaluated. Recurrent new DUs were defined as the presence of at least 3 episodes of DUs in a 12-months follow up period. The risk of developing new DUs was calculated by applying the capillaroscopic skin ulcer risk index (CSURI).

Results

The median value of TSLP was higher in patients with HDU than patients without HDU [181.67 pg/ml (IQR 144.67; 265.66) vs 154.67 pg/ml (IQR 110.67; 171.33), p < 0.01]. The median value of TSLP was higher in patients with an increased CSURI index than patients without an increased CSURI [188 pg/ml (IQR 171.33; 246.33) vs 159.33 pg/ml (IQR 128.67; 218), p < 0.01]. Kaplan-Meier curves demonstrated that free survival from new DUs was significantly (p < 0.01) lower in SSc patients with increased TSLP serum levels.

Conclusion

TSLP might have a key role in digital microvascular damage of SSc patients.

Introduction

Septic shock is a systemic infection that causes persistent systemic hypotension, inflammation, tissue hypoperfusion and acute kidney injury (AKI). Despite norepinephrine being the currently recommended vasopressor agent, an alternative vasopressor agent that positively affects peripheral and organ microcirculatory perfusion and oxygenation is needed. This study investigated a new synthetic Angiotensin II agent suitable for improving microcirculatory parameters in a rat model of sepsis-induced systemic hemodynamic dysfunction.

Methods

48 mechanically ventilated, anesthetized male rats were allocated as control; lipopolysaccharide (LPS, 20 mg/kg) and LPS groups received either ringer acetate (RA), norepinephrine (NE), Angiotensin II (Ang II), or a combination of NE and Ang II. Systemic hemodynamics, renal cortical pO₂ and perfusion, and muscle microcirculatory oxygen saturation were evaluated.

Results

MAP was restored in all LPS groups that received Ang II, NE, and NE + Ang II compared to the LPS group alone (p < 0.05). The deterioration of renal microcirculatory cortical oxygen, oxygen delivery, and consumption after sepsis was not restored by any of the resuscitation strategies. However, urine output was improved after Ang II resuscitation compared to the LPS and LPS + RA groups (p < 0.05). Furthermore, the muscle capillary oxygen saturation and functional capillary density (FCD) were improved by a combined infusion of NE and Ang II (p < 0.05).

Conclusions

Ang II can improve the MAP in rats in a way comparable to norepinephrine. Ang II increased urine output and muscle capillary oxygenation and reduced renal tissue damage. Our study supports that broad-spectrum vasopressors can benefit tissue perfusion and oxygenation in the resuscitation of septic patients.

Peripheral artery disease (PAD) is the manifestation of atherosclerosis characterized by the accumulation of plaques in the arteries of the lower limbs. Interestingly, growing evidence suggests that the pathology of PAD is multifaceted and encompasses both vascular and skeletal muscle dysfunctions, which contributes to blunted physical capabilities and diminished quality of life. Importantly, it has been suggested that many of these pathological impairments may stem from blunted reduction-oxidation (redox) handling. Of note, in those with PAD, excessive production of reactive oxygen species (ROS) outweighs antioxidant capabilities resulting in oxidative damage, which may have systemic consequences. It has been suggested that antioxidant supplementation may be able to assist in handling ROS. However, the activation of various ROS production sites makes it difficult to determine the efficacy of these antioxidant supplements. Therefore, this review focuses on the common cellular mechanisms that facilitate ROS production and discusses how excessive ROS may impair vascular and skeletal muscle function in PAD. Furthermore, we provide insight for current and potential antioxidant therapies, specifically highlighting activation of the Kelch-like ECH-associated protein 1 (Keap1) - Nuclear Factor Erythroid 2-related factor 2 (Nrf2) pathway as a potential pharmacological therapy to combat ROS accumulation and aid in vascular function, and physical performance in patients with PAD. Altogether, this review provides a better understanding of excessive ROS in the pathophysiology of PAD and enhances our perception of potential therapeutic targets that may improve vascular function, skeletal muscle function, walking capacity, and quality of life in patients with PAD.

Background

Leprosy, a chronic infectious disease, is associated with various nail changes. Its etiopathogenesis is multifaceted, with microvascular damage being crucial. Nail fold capillaroscopy (NFC) emerges as a novel tool for detecting early vascular deficits in leprosy. The study aimed to assess and provide a complete clinical characterization of NFC changes in leprosy patients.

Methods

It is an observational cross-sectional study, done over a period of 1.5 year (January 2021 to august 2022) in a tertiary care hospital, encompassing 60 patients diagnosed with leprosy (18–60 years). After obtaining informed consent; detailed history, complete cutaneous and neurological examinations were conducted. All fingernails and toenails were examined for clinical changes. Subsequently, onychoscopy was performed using USB type of video-dermatoscope (Model AM7115MZT Dino-lite), a non-invasive tool. This was followed by NFC which was done for all fingernails and images were recorded by single operator, which were then assessed for quantitative and qualitive changes and statistical analysis was conducted using SPSS v20, with mean capillary density compared using Student's t-test, morphological change frequencies assessed by proportions, and group comparisons made using Chi-square or Fischer exact tests, with a significance threshold of p < 0.05.

Results

Among the 60 patients, 39 were in the lepromatous group, which included both borderline lepromatous (BL) and lepromatous leprosy (LL) patients, and 17 were in the tuberculoid group, which included borderline tuberculoid (BT) leprosy patients; 23.3 % had Type 1 reactions, and 18.3 % had Type 2 reactions. Nail fold capillaroscopy (NFC) showed microvasculature changes in 93.3 % of patients. The average capillary density was 6.8 ± 1.5 capillaries per mm, with the lepromatous group having a lower density (6.5 ± 1.09) compared to the tuberculoid group (7.0 ± 0.86). The most common NFC changes in the tuberculoid group were tortuous capillaries (70 %), capillary dropouts, and dilated capillaries (both 64.7 %). In the lepromatous group, capillary dropouts (82 %) were most frequent, followed by tortuous (69 %), receding (69 %), and dilated capillaries (66 %). A dilated and prominent subpapillary plexus was more common in the lepromatous group (35 %, p = 0.04). Patients with trophic changes in the lepromatous group had more capillary dropouts and bizarre capillaries. Capillary dropouts, dilated capillaries, and visible subpapillary venous plexus were more prevalent in patients with Type 2 reactions.

Conclusion

NFC changes are prevalent in both tuberculoid and lepromatous leprosy, which may be an indicator of peripheral vascular compromise and trophic changes, especially in lepromatous leprosy. NFC can be an auxiliary tool for detecting microvascular abnormalities in leprosy patients.

Patients with Takotsubo syndrome displayed endothelial dysfunction, but underlying mechanisms have not been fully clarified. This study aimed to explore molecular signalling responsible for catecholamine excess induced endothelial dysfunction.

Human cardiac microvascular endothelial cells were challenged by epinephrine to mimic catecholamine excess. Patch clamp, FACS, ELISA, PCR, and immunostaining were employed for the study.

Epinephrine (Epi) enhanced small conductance calcium-activated potassium channel current (I_SK1–3) through activating α1 adrenoceptor. Phenylephrine enhanced edothelin-1 (ET-1) and reactive oxygen species (ROS) production, and the effects involved contribution of I_SK1–3. H₂O₂ enhanced I_SK1–3 and ET-1 production. Enhancing I_SK1–3 caused a hyperpolarization, which increases ROS and ET-1 production. BAPTA partially reduced phenylephrine-induced enhancement of ET-1 and ROS, suggesting that α1 receptor activation can enhance ROS/ET-1 generation in both calcium-dependent and calcium-independent ways.

The study demonstrates that high concentration catecholamine can activate SK1–3 channels through α1 receptor-ROS signalling and increase ET-1 production, facilitating vasoconstriction.