microvascular damage
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2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Elisha D. O. Roberson ◽  
Rosana A. Mesa ◽  
Gabrielle A. Morgan ◽  
Li Cao ◽  
Wilfredo Marin ◽  
...  

AbstractIn juvenile dermatomyositis (JDM), the most common pediatric inflammatory myopathy, weakness is accompanied by a characteristic rash that often becomes chronic and is associated with vascular damage. We hoped to understand the molecular underpinnings of JDM, particularly when untreated, which would facilitate the identification of novel mechanisms and clinical targets that might disrupt disease progression. We studied the RNA-Seq data from untreated JDM peripheral blood mononuclear cells (PBMCs; n = 11), PBMCs from a subset of the same patients when clinically inactive (n = 8/11), and separate samples of untreated JDM skin and muscle (n = 4 each). All JDM samples were compared to non-inflammatory control tissues. The untreated JDM PBMCs showed a strong signature for type1 interferon response, along with IL-1, IL-10, and NF-κB. Surprisingly, PBMCs from clinically inactive JDM individuals had persistent immune activation that was enriched for IL-1 signaling. JDM skin and muscle both showed evidence for type 1 interferon activation and genes related to antigen presentation and decreased expression of cellular respiration genes. Additionally, we found that PBMC gene expression correlates with disease activity scores (DAS; skin, muscle, and total domains) and with nailfold capillary end row loop number (an indicator of microvascular damage). This included otoferlin, which was significantly increased in untreated JDM PBMCs and correlated with all 3 DAS domains. Overall, these data demonstrate that PBMC transcriptomes are informative of molecular disruptions in JDM and provide transcriptional evidence of chronic inflammation despite clinical quiescence.


2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Shao-Yang Zhao ◽  
Huan-Huan Zhao ◽  
Yi-Ming Li ◽  
Bao-Hua Wang ◽  
Sai-Mei Li

Diabetic cognitive dysfunction is a serious complication of type 2 diabetes mellitus (T2DM), which can cause neurological and microvascular damage in the brain. At present, there is no effective treatment for this complication. Bushen Huoxue prescription (BSHX) is a newly formulated compound Chinese medicine containing 7 components. Previous research indicated that BSHX was neuroprotective against advanced glycosylation end product (AGE)-induced PC12 cell insult; however, the effect of BSHX on AGE-induced cerebral microvascular endothelia injury has not been studied. In the current research, we investigated the protective effects of BSHX on AGE-induced injury in bEnd.3 cells. Our findings revealed that BSHX could effectively protect bEnd.3 cells from apoptosis. Moreover, we analyzed the network regulation effect of BSHX on AGE-induced bEnd.3 cells injury at the proteomic level. The LC-MS/MS-based shotgun proteomics analysis showed BSHX negatively regulated multiple AGE-elicited proteins. Bioinformatics analysis revealed these differential proteins were involved in multiple processes, such as Foxo signaling pathway. Further molecular biology analysis confirmed that BSHX could downregulate the expression of FoxO1/3 protein and inhibit its nuclear transfer and inhibit the expression of downstream apoptotic protein Bim and the activation of caspase, so as to play a protective role in AGE-induced bEnd.3 injury. Taken together, these findings demonstrated the role of BSHX in the management of diabetic cerebral microangiopathy and provide some insights into the proteomics-guided pharmacological mechanism study of traditional Chinese Medicine.


2021 ◽  
Vol 21 (8) ◽  
pp. 485-495
Author(s):  
Joshua Cronin-Lampe ◽  
Alana Cavadino ◽  
Harris Ansari ◽  
Faufiva Fa'alau ◽  
Judith Mccool

Abstract Objectives: Diabetic retinopathy (DR) is one of the primary causes of preventable vision loss and blindness. Diabetic retinopathy screening (DRS) is essential to detect microvascular damage to the retina; it can be performed in primary care or specialist eye health clinics. The system of referral, screening, and treatment relies on an organized primary care referral pathway, accessible services, and at least a basic level of health literacy among those living with or under threat of developing Diabetes Mellitus (DM).   Methods: Routinely collected patient data from the Pacific Eye Institute (PEI) in Fiji was analyzed to describe a) clinical and demographic DR patient characteristics and b) characteristics of patients demonstrating higher clinic engagement (using multiple logistic regression).   Results: Of 9287 patients who first attended the PEI for DRS between 2012 and 2017, 22% presented with sight-threatening diabetic retinopathy (STDR) in at least one eye. The average duration of DM was 3 years; self-reported glycaemic control was poor. Indo-Fijian or other ethnicity (both vs iTaukei, OR=2.30, 95%CI 1.96-2.70 and OR=2.18, 95% CI 1.63-2.92, respectively; p<0.001), high blood sugar (OR 1.39, 95%CI 1.10-1.75, p=0.006), longer duration of disease (OR=1.21, 95%CI 1.02-1.43, p=0.027), peripheral neuropathy (OR=1.43, 95%CI 1.24-1.65, p<0.001) and STDR (OR=3.30, 95%CI 2.78-3.92, p<0.001) were associated with greater odds of higher clinic engagement. Male gender (Odds Ratio (OR)=0.83, 95% Confidence Interval (CI) 0.72-0.95, p=0.006), younger or older age (both vs 40-70 years; <40 years, OR=0.48, 95%CI 0.37-0.63, ?70 years OR=0.61, 95%CI 0.48-0.76, p<0.001), year of first clinic visit (2013 vs 2012 OR=0.58, 95%CI 0.50-0.69, p<0.001; 2014 vs 2012 OR=0.36, 95%CI 0.30-0.43, p<0.001) and moderate visual impairment (OR=0.67 95%CI 0.56-0.80, p<0.001) were associated with lower odds of high clinic engagement.   Conclusion: Our results identify patient groups that may be more vulnerable to lower engagement with eye health services. Increasing engagement may help reduce delays in screening and treatment. Given the projected continued rise in DM in the Pacific region, investing in robust electronic data systems that collect and connect public health and clinical data is imperative. Health literacy is important for the prevention of DM, timely DM diagnosis, and screening for complications such as DR.


Neurology ◽  
2021 ◽  
Vol 98 (1 Supplement 1) ◽  
pp. S15.3-S16
Author(s):  
Nicholas Kayode Da Silva Soyombo ◽  
Emanuelle Lamas Rocha ◽  
Larissa Batista Xavier ◽  
Rafael Arantes Oliveira ◽  
Rodrigo Torres

ObjectiveTo assess the diagnostic utility of biomarkers that could differentiate Chronic Traumatic Encephalopathy (CTE) from Alzheimer disease (AD).BackgroundCTE is a neurodegenerative disease associated with multiple head trauma. The diagnosis depends on neuropathologic findings postmortem, and patients can present cognitive and behavioral changes. These symptoms can usually be mistaken for other dementias, such as AD, leading to an underestimated frequency of CTE. Therefore, specific biomarkers can be useful for comprehending disease development, diagnosis and prognosis.Design/MethodsWe systematically searched the MEDLINE, Embase and Cochrane databases. We also searched the trial registries and reference lists of articles. We included studies that were relevant to the PICO question posed and analysed different biomarkers. We screened titles and abstracts and if they were pertinent, we assessed the full text and reported results narratively.ResultsTwenty-two studies were identified through database searching. One study was excluded due to duplicity among the databases. Twenty-one articles were assessed for eligibility and 6 were included in the qualitative synthesis. P-Tau and T-tau proteins were indicated as biomarkers of neurodegenerative diseases such as CTE and AD, but not from other tauopathies. Exosomal tau levels are higher in CTE patients than in AD patients, and it might be useful since it is very stable, crosses the blood–brain barrier and reflects their cellular origin. Pathophysiologic differences between CTE and AD are pointed out as a way to find specific biomarkers for CTE. The biomarkers associated with neuroaxonal damage (NFL), glial response with astroglial scarring (GFAP and sTREM2), and microvascular damage with disruption of the blood–brain barrier (cerebrospinal fluid/serum albumin ratio) are promising in that way.ConclusionsBiomarkers that arise from pathophysiologic processes distinct from the 2 diseases, appear to be promising. However, further well-designed studies are needed to assess the real utility of the biomarkers in differential diagnosis between CTE and AD.


2021 ◽  
Vol 8 ◽  
Author(s):  
Eleni Pagkopoulou ◽  
Stergios Soulaidopoulos ◽  
Eva Triantafyllidou ◽  
Afrodite Malliari ◽  
George D. Kitas ◽  
...  

Objective: The key element in the pathogenesis of systemic sclerosis (SSc) is microcirculatory changes in several vascular beds. Uric acid is associated with endothelial dysfunction and therefore, microvascular damage. The aim of this study was to examine the association between uric acid (UA) and peripheral microvascular involvement in patients with SSc.Methods: We included consecutive, consenting patients with SSc. Serum UA, urea and creatinine were measured, and glomerular filtration rate (GFR) was calculated with CKD-EPI. All participants underwent nailfold video-capillaroscopy (NVC) to evaluate the microcirculation.Results: A total of 64 patients (95.3% women) were included in the study. UA levels were significantly associated with the number of avascular areas (r = 0.290; p = 0.020), whereas no correlation was shown for the GFR (r = −0.065; p = 0.609). A significant trend of UA in the three capillaroscopic patterns was shown (3.90 ± 1.52 vs. 4.15 ± 0.98 vs. 5.38 ± 2.26; for early, active, and late patterns respectively, p = 0.028). Multivariate analysis showed that male gender (β = 3.049; 95% CI = 0.997–5.101) and UA (β = 0.352; 95% CI = 0.117–0.588) were independently associated with the number of avascular areas.Conclusion: These data suggest that UA levels are significantly associated with the capillaroscopic patterns, reflecting a progressive microvasculopathy.


2021 ◽  
Vol 12 ◽  
Author(s):  
Chun-Shui Pan ◽  
Li Yan ◽  
Se-Qi Lin ◽  
Ke He ◽  
Yuan-Chen Cui ◽  
...  

Aims: Coronary microvascular hyperpermeability is an important contributor to ischemia or reperfusion (I/R) injury. However, the effective strategy for this insult remains limited. This study aimed to explore the protective effect of the compound Chinese medicine QiShenYiQi Pills (QSYQ) against coronary microvascular hyperpermeability after cardiac I/R with focusing on the underlying mechanism.Methods and Results: Male Sprague-Dawley rats under anesthesia were subjected to occlusion of left coronary anterior descending artery followed by reperfusion. QSYQ was administrated 90 min before ischemia initiation. Human cardiac microvascular endothelial cells (HCMECs) underwent hypoxia or reoxygenation (H/R) challenge with QSYQ administrated 1 h prior to hypoxia. QSYQ exhibited effects on attenuating microvascular damage and albumin leakage after I/R injury, showing a role in maintaining endothelial junctions, caveolae, and collagen in basement membrane (BM) of microvessels. Study using HCMECs disclosed that QSYQ protected endothelial barrier from impairment by H/R, attenuating the decline of respiratory chain complex I and ATP synthase, activation of Src/caveolin-1 and increase of RhoA/ROCK/p-MLC, MMP-9, and CTSS. PP2, a Src inhibitor, partially imitated the effect of QSYQ.Conclusions: The QSYQ was able to prevent I/R-induced cardiac microvascular hyperpermeability via a mechanism involving Src/caveolin-1 and RhoA/ROCK/MLC signaling.


2021 ◽  
Vol 8 ◽  
Author(s):  
Pingting Zhong ◽  
Yijun Hu ◽  
Lei Jiang ◽  
Qingsheng Peng ◽  
Manqing Huang ◽  
...  

Background: Retinal microvasculature has been associated with coronary artery disease (CAD), but the exact contributory role in coronary total occlusion (CTO) is unclear. We aimed to investigate whether retinal vasculature is associated with CTO and could provide incremental value in the assessment of CTO.Methods: A total of 218 CAD patients including 102 CTO and 116 non-CTO were enrolled. Retinal vasculature was measured by optical coherence tomography angiography (OCTA) for all patients. Receiver operating characteristic (ROC) curve was used to assess the performance of retinal vasculature in differentiating CTO from non-CTO patients.Results: In non-CTO CAD patients, vessel density (VD) of mean superficial capillary plexus (SCP) and parafovea SCP were 49.85 and 52.56%, respectively; in CTO patients, VD of mean SCP and parafovea SCP were 47.77, and 49.58%, respectively. After multiple adjustment, VD in the SCP was significantly lower in CTO patients compared to non-CTO patients. VD of superior hemi in the parafovea SCP combined with the clinical variates showed the best ability to predict CTO from CAD with an area under the curve (AUC) of 0.812 (specificity of 89.0% and sensitivity of 65.9%).Conclusions: In CTO patients, retinal VD was significantly decreased, and microvascular damage might specifically target to arterioles than capillaries. Retinal vasculature could thus be a surrogate for detecting the microvascular damage and assist in the assessment of CTO patients. OCTA examination could be suggested to monitor the process of coronary arteries lesions.


2021 ◽  
Vol 25 (1) ◽  
pp. 9-15
Author(s):  
E. V. Dvoryankova ◽  
I. M. Korsunskaya ◽  
T. A. Slavyanskaya

The infection caused by the recently identified SARS-CoV-2, dubbed coronavirus disease-19 (COVID-19), has become a pandemic. With exponential growth of morbidity among the people around the world, the clinical characteristics of COVID-19 are becoming clearer and description of new disease symptoms descriptions is emerging. The sufficient amount of descriptions of various skin manifestations in patients with COVID-19 has appeared, however they are characterized by great heterogeneity. The pathogenetic mechanisms of the development of skin rashes in patients with COVID-19 are currently unknown, however, hypotheses have been put forward that they have an overactive immune response, activation of the complement system and microvascular damage. Based on the published literature data and our own experience, the following characteristic types of skin rashes can be distinguished among the skin manifestations of this viral disease: urticaria, confluent, papulovesicular exanthema, acral rashes similar to frostbite, livedo reticularis and purpura. Possible development of skin lesions against the background of the development of COVID-19 provides the need to inform dermatologists about the features of the skin manifestations of this disease, as well as to study further these symptoms of COVID-19 to determine their diagnostic and prognostic value.


2021 ◽  
Vol 8 ◽  
Author(s):  
Boris Schnorbus ◽  
Kerstin Jurk ◽  
Karl J. Lackner ◽  
Caroline Welk ◽  
Thomas Münzel ◽  
...  

Aims: In this pre-specified analysis of the “endothelium, stent and antiplatelet therapy” study, we investigate the impact of antiplatelet therapies on microvascular function in patients undergoing stenting for an acute coronary syndrome.Methods and Results: Fifty-six patients [age: 63(55–67) years, males, 10 diabetics, 27 non-ST-elevation myocardial infarction] were randomized to receive clopidogrel, ticagrelor or prasugrel in form of oral loading 2 h before stenting followed by oral therapy. Investigators were blinded to the allocation. Laser-Doppler microvascular function and ADP-induced platelet aggregation capacity were measured at baseline, 2 h after oral antiplatelet loading, and 1 day, 1 week and 1 month after stenting during chronic therapy with the same antiplatelet agent. Platelet aggregation decreased in all groups 2 h after oral loading, with a significantly larger effect in the prasugrel group (P = 0.009). Similarly, prasugrel and ticagrelor loading was followed by an increase in microvascular reactive hyperemia (P = 0.007 and P = 0.042 compared to clopidogrel). This effect disappeared one day after coronary intervention, with a significant decrease in the prasugrel group (P = 0.026). Similarly, analysis of microvascular conductance showed a larger increase in the prasugrel group 2 h after loading (P = 0.022 among groups), and a decrease in all groups after stenting.Conclusions: Oral loading with prasugrel (and less consistently ticagrelor) is associated with improved microvascular function and stronger platelet inhibition in acute coronary syndrome patients. The microvascular effect was however lost 1 day after stenting and during subsequent follow-up. Further studies are necessary to clarify the the long-term effects and potential benefits of P2Y12 inhibitors on microvascular damage.ClINICALTRIALS.gov N°: NCT01700322EUDRACT-N°: 2011-005305-73.


Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1861
Author(s):  
Dominga Lapi ◽  
Maurizio Cammalleri ◽  
Massimo Dal Monte ◽  
Martina Di Maro ◽  
Maria Rosaria Santillo ◽  
...  

Renin–angiotensin systems produce angiotensin II (Ang II) and angiotensin 1-7 (Ang 1-7), which are able to induce opposite effects on circulation. This study in vivo assessed the effects induced by Ang II or Ang 1-7 on rat pial microcirculation during hypoperfusion–reperfusion, clarifying the mechanisms causing the imbalance between Ang II and Ang 1-7. The fluorescence microscopy was used to quantify the microvascular parameters. Hypoperfusion and reperfusion caused vasoconstriction, disruption of blood–brain barrier, reduction of capillary perfusion and an increase in reactive oxygen species production. Rats treated with Ang II showed exacerbated microvascular damage with stronger vasoconstriction compared to hypoperfused rats, a further increase in leakage, higher decrease in capillary perfusion and marker oxidative stress. Candesartan cilexetil (specific Ang II type 1 receptor (AT1R) antagonist) administration prior to Ang II prevented the effects induced by Ang II, blunting the hypoperfusion–reperfusion injury. Ang 1-7 or ACE2 activator administration, preserved the pial microcirculation from hypoperfusion–reperfusion damage. These effects of Ang 1-7 were blunted by a Mas (Mas oncogene-encoded protein) receptor antagonist, while Ang II type 2 receptor antagonists did not affect Ang 1-7-induced changes. In conclusion, Ang II and Ang 1-7 triggered different mechanisms through AT1R or MAS receptors able to affect cerebral microvascular injury.


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