Search Results (636)

Background: To date, it is not well known which systemic pathologies most frequently afflict patients with rotator cuff tear (RCT) and whether the coexistence of two or more pathologies can affect the lesion size. Therefore, we analyzed our database relative to a large group of patients who recently underwent rotator cuff repair. Methods: A total of 527 patients with full-thickness RCT were enrolled. For each patient, we checked the presence of at least one of diabetes, venous system diseases, cardiovascular diseases, hypercholesterolemia, blood hypertension, thyroid diseases, and a smoking habit. Patients were subdivided according to risk factors into five groups, representing those who had zero, one, two, three, and four or more risk factors, respectively. Statistical analysis was performed. Results: In total, 37% of our patients had no risk factors; 28% had one risk factor (arterial hypertension, smoking habit, and hypercholesterolemia were the most frequent); 23% had two risk factors (the hypertension/hypercholesterolemia association was the most frequent); and 8% suffered from three pathologies (the diabetes/arterial hypertension/hypercholesterolemia association was the most frequent). Comparing the cuff tear severity in patients without and with at least one risk factor, we observed that tear size increased in those with at least one risk factor. Conclusions: A total of 63% of patients with rotator cuff tears were either smokers and/or had at least one pathology capable of altering the peripheral microcirculation. Hypertension and hypercholesterolemia were the most frequent. Tear severity significantly increased with the presence of at least one risk factor. Full article

Perfusion asymmetries have been associated with vascular pathology. Physical activity is a component of vascular health. Here, we investigate the impact of a thirty-day regular home-based physical activity program in older individuals with multiple age-related comorbidities. Eleven participants of both sexes were included. Skin perfusion was assessed in both feet by laser Doppler flowmetry (LDF, for deeper perfusion) and polarized light spectroscopy (PSp, for superficial perfusion). At baseline, participants had significant perfusion differences between right and left feet (p = 0.005 with LDF; p = 0.028 with PSp), which disappeared with activity and reappeared in recovery. After 30 days, both feet showed significant perfusion increases as assessed with LDF (p = 0.005) compared to D0. At this point, the perfusion asymmetry observed at D0 was no longer present. However, the superficial perfusion asymmetry assessed by PSp persisted at D30 (p = 0.028). Data show that regular physical activity positively altered the lower limb perfusion pattern. Systolic pressure and mean arterial pressure were also significantly reduced at D30. These impacts seem to be directly related to the physical activity program introduced in the day-by-day routines of these participants. These also encourage further research on the role of symmetry–asymmetry in prevention, treatment, and rehabilitation in vascular medicine. Full article

Oxidative stress plays a major role in the formation of the cataract that is the result of advancing age, diabetes or which follows vitrectomy surgery. Glutathione (GSH) is the principal antioxidant in the lens, and so supplementation with GSH would seem like an intuitive strategy to counteract oxidative stress there. However, the delivery of glutathione to the lens is fraught with difficulties, including the limited bioavailability of GSH caused by its rapid degradation, anatomical barriers of the anterior eye that result in insufficient delivery of GSH to the lens, and intracellular barriers within the lens that limit delivery of GSH to its different regions. Hence, more attention should be focused on alternative methods by which to enhance GSH levels in the lens. In this review, we focus on the following three strategies, which utilize the natural molecular machinery of the lens to enhance GSH and/or antioxidant potential in its different regions: the NRF2 pathway, which regulates the transcription of genes involved in GSH homeostasis; the use of lipid permeable cysteine-based analogues to increase the availability of cysteine for GSH synthesis; and the upregulation of the lens’s internal microcirculation system, which is a circulating current of Na⁺ ions that drives water transport in the lens and with it the potential delivery of cysteine or GSH. The first two strategies have the potential to restore GSH levels in the epithelium and cortex, while the ability to harness the lens’s internal microcirculation system offers the exciting potential to deliver and elevate antioxidant levels in its nucleus. This is an important distinction, as the damage phenotypes for age-related (nuclear) and diabetic (cortical) cataract indicate that antioxidant delivery must be targeted to different regions of the lens in order to alleviate oxidative stress. Given our increasing aging and diabetic populations it has become increasingly important to consider how the natural machinery of the lens can be utilized to restore GSH levels in its different regions and to afford protection from cataract. Full article

Aim: The primary endothelial NADPH oxidase isoform 4 (NOX4) is notably induced during hypoxia, with emerging evidence suggesting its vasoprotective role through H₂O₂ production. Therefore, we aimed to elucidate NOX4′s significance in endothelial function under hypoxia. Methods: Human vessels, in addition to murine vessels from Nox4^−/− mice, were explored. On a functional level, Mulvany myograph experiments were performed. To obtain mechanistical insights, human endothelial cells were cultured under hypoxia with inhibitors of hypoxia-inducible factors. Additionally, endothelial cells were cultured under combined hypoxia and laminar shear stress conditions. Results: In human occluded vessels, NOX4 expression strongly correlated with prostaglandin I2 synthase (PTGIS). Hypoxia significantly elevated NOX4 and PTGIS expression and activity in human endothelial cells. Inhibition of prolyl hydroxylase domain (PHD) enzymes, which stabilize hypoxia-inducible factors (HIFs), increased NOX4 and PTGIS expression even under normoxic conditions. NOX4 mRNA expression was reduced by HIF1a inhibition, while PTGIS mRNA expression was only affected by the inhibition of HIF2a under hypoxia. Endothelial function assessments revealed hypoxia-induced endothelial dysfunction in mesenteric arteries from wild-type mice. Mesenteric arteries from Nox4^−/− mice exhibited an altered endothelial function under hypoxia, most prominent in the presence of cyclooxygenase inhibitor diclofenac to exclude the impact of prostacyclin. Restored protective laminar shear stress, as it might occur after thrombolysis, angioplasty, or stenting, attenuated the hypoxic response in endothelial cells, reducing HIF1a expression and its target NOX4 while enhancing eNOS expression. Conclusions: Hypoxia strongly induces NOX4 and PTGIS, with a close correlation between both factors in occluded, hypoxic human vessels. This relationship ensured endothelium-dependent vasodilation under hypoxic conditions. Protective laminar blood flow restores eNOS expression and mitigates the hypoxic response on NOX4 and PTGIS. Full article

This review summarizes studies dedicated to the assessment of microvascular function based on microcirculatory oscillations monitored by the Flow-Mediated Skin Fluorescence (FMSF) technique. Two approaches are presented. The first approach uses oscillatory parameters measured under normoxic conditions, expressed as flowmotion (FM), vasomotion (VM), and the normoxia oscillatory index (NOI). These parameters have been used for the identification of impaired microcirculatory oscillations associated with intense physical exercise, post-COVID syndrome, psychological stress, and erectile dysfunction. The second approach involves characterization of the microcirculatory response to hypoxia based on the measurement of hypoxia sensitivity (HS). The HS parameter is used to characterize microvascular complications in diabetes, such as diabetic kidney disease and diabetic foot ulcers. Based on research conducted by the authors of this review, the FMSF parameter ranges characterizing microvascular function are presented. The diagnostic approach to assessing microvascular function based on flowmotion monitored by the FMSF technique has a wide range of applications and the potential to be integrated into widespread medical practice. Full article

Background: The study aimed to evaluate the immediate effect of Heat-Compression-Therapy with Game Ready equipment (GR-HCT) on biomechanical properties at different treatment times. Reducing the duration of stimulation through HCT can help optimize recovery processes in sports. Methods: Twenty male MMA fighters (26.5 ± 4.5 years, BMI 24.75 ± 3.0, training experience: 10.3 ± 5.0 years) performed two experimental sessions: (a) 5 min heat-compression therapy (HCT) stimulation (GR-HCT-5); and (b) 10 min heat-compression therapy (GR-HCT-10). All registered parameters, tissue perfusion (PU), tissue temperature (°C), muscle tone (T-Hz) stiffness (S—N/m), elasticity (E—arb), pressure pain threshold (PPT—N/cm) and isometric muscle strength (Fmax—kgf), were measured at rest (r—2 min before GR-HCT stimulation) and 1 min after GR-HCT (p-post) for the flexor carpi radialis muscle (MFCR) and the brachioradialis muscle (MBR). Results: The Friedman’s test for MBR revealed significant differences between GR-HCT5min vs. GR-HCT10min for PU (p < 0.0001), S (p = 0.008), and for MBR and MFCR for °C (p < 0.0001). The pairwise comparisons for PU, S, and °C showed significant differences between rest vs. post values for 5 min as well as between rest vs. post values for 10 min. Further, there was a significant interaction effect (5 min-10 min × Rest-Post p < 0.0001) for PU for MFCR. The post hoc comparison for the interaction effect showed significantly higher PU for post- compared to premeasurement in 5 min PU and 10 min PU (p < 0.001). Further, there was a significant main effect of condition for Fmax both for MFCR and MBR (5 min vs. 10 min p < 0.001); The post hoc comparison for the main effect of condition showed a significantly higher Fmax for post- compared to premeasurement in 5 min and 10 min (p < 0.001). Further, there was a significant main effect of condition for pressure pain threshold [N/cm] both for MFCR and MBR and for T for MBR time of measurement rest vs. post (p < 0.001; p = 0.006; p < 0.001, respectively). The post hoc comparison for the interaction effect showed a significantly lower PPT for post vs. rest in 5 min (p < 0.001 only for MFCR) and in 10 min (p < 0.001). The delta values for PU (post-rest) and ΔTemp °C showed significant differences between the 5 min and 10 min conditions (MFCR; p < 0.0001); (MBR p < 0.001) and (MFCR p < 0.0001); (MBR p < 0.001). Conclusion: Our results show that GR-HCT significantly affects recovery of muscle biomechanical parameters, pain threshold, strength, tissue perfusion, and temperature. Our findings show that a 5 min effect can be sufficient when compared to a 10 min one which is a clue for designing effective recovery protocols. Full article

Cell–cell adhesion in endothelial monolayers is tightly controlled and crucial for vascular integrity. Recently, we reported on the importance of fast protein turnover for maintenance of endothelial barrier function. Specifically, continuous ubiquitination and degradation of the Rho GTPase RhoB is crucial to preserve quiescent endothelial integrity. Here, we sought to identify other barrier regulators, which are characterized by a short half-life, using a proteomics approach. Following short-term inhibition of ubiquitination with E1 ligase inhibitor MLN7243 or Cullin E3 ligase inhibitor MLN4924 in primary human endothelial cells, we identified sixty significantly differentially expressed proteins. Intriguingly, our data showed that AAMP and MTSS1 are novel negative regulators of endothelial barrier function and that their turnover is tightly controlled by ubiquitination. Mechanistically, AAMP regulates the stability and activity of RhoA and RhoB, and colocalizes with F-actin and cortactin at membrane ruffles, possibly regulating F-actin dynamics. Taken together, these findings demonstrate the critical role of protein turnover of specific proteins in the regulation of endothelial barrier function, contributing to our options to target dysregulation of vascular permeability. Full article

Introduction: Nailfold video-capillaroscopy (NVC) is a non-invasive cost-effective technique involving the microscopic examination of small blood vessels of the distal nailfold with a magnification device. It provides valuable information regarding the microcirculation including anomalies such as tortuous or dilated capillaries, hemorrhages, and avascular areas, which can characterize connective tissue diseases. The utility of NVC in the diagnosis and monitoring of systemic sclerosis (SSc) has been investigated in numerous studies allowing the distinction of the specific microvascular pattern of scleroderma from different conditions other than scleroderma (non-scleroderma pattern). Sarcoidosis (SA) is a systemic inflammatory disease that can affect various organs, including the lungs, skin, and lymph nodes. The purpose of our review was to evaluate the current state of the art in the use of NVC in the diagnosis of SA, to understand the indications for its use and any consequent advantages in the management of the disease in different settings in terms of benefits for patients. Materials and Methods: We searched for the key terms “sarcoidosis” and “video-capillaroscopy” in a computerized search of Pub-Med, extending the search back in time without setting limits. We provided a critical overview of the literature, based on a precise evaluation. After our analysis, we examined the six yielded works looking for answers to our questions. Results: Few studies have evaluated that microcirculation is often compromised in SA, with alterations in blood flow and consequent tissue damage. Discussion: Basing on highlighted findings, NVC appears to be a useful tool in the initial evaluation of sarcoidosis patients. Furthermore, capillaroscopy is useful in the evaluation of the coexistence of sarcoidosis and scleroderma spectrum disorder or overlap syndromes. Conclusions: In conclusions, no specific pattern has been described for sarcoidosis, and further re-search is needed to fully understand the implications of nailfold capillaroscopy find-ings in this disease and to establish standardized guidelines for its use in clinical practice. Full article

Cardiovascular diseases (CVDs) are a major cause of mortality globally, emphasizing the need for early detection and effective risk assessment to improve patient outcomes. Advances in oculomics, which utilize the relationship between retinal microvascular changes and systemic vascular health, offer a promising non-invasive approach to assessing CVD risk. Retinal fundus imaging and optical coherence tomography/angiography (OCT/OCTA) provides critical information for early diagnosis, with retinal vascular parameters such as vessel caliber, tortuosity, and branching patterns identified as key biomarkers. Given the large volume of data generated during routine eye exams, there is a growing need for automated tools to aid in diagnosis and risk prediction. The study demonstrates that AI-driven analysis of retinal images can accurately predict cardiovascular risk factors, cardiovascular events, and metabolic diseases, surpassing traditional diagnostic methods in some cases. These models achieved area under the curve (AUC) values ranging from 0.71 to 0.87, sensitivity between 71% and 89%, and specificity between 40% and 70%, surpassing traditional diagnostic methods in some cases. This approach highlights the potential of retinal imaging as a key component in personalized medicine, enabling more precise risk assessment and earlier intervention. It not only aids in detecting vascular abnormalities that may precede cardiovascular events but also offers a scalable, non-invasive, and cost-effective solution for widespread screening. However, the article also emphasizes the need for further research to standardize imaging protocols and validate the clinical utility of these biomarkers across different populations. By integrating oculomics into routine clinical practice, healthcare providers could significantly enhance early detection and management of systemic diseases, ultimately improving patient outcomes. Fundus image analysis thus represents a valuable tool in the future of precision medicine and cardiovascular health management. Full article

Background: Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) infection can cause feared consequences, such as affecting microcirculatory activity. The combined use of HRV analysis, genetic algorithms, and machine learning classifiers can be helpful in better understanding the characteristics of microcirculation that are mainly affected by COVID-19 infection. Methods: This study aimed to verify the presence of microcirculation alterations in patients with COVID-19 infection, performing Heart Rate Variability (HRV) parameters analysis extracted from PhotoPlethysmoGraphy (PPG) signals. The dataset included 97 subjects divided into two groups: healthy (50 subjects) and patients affected by mild-severity COVID-19 (47 subjects). A total of 26 parameters were extracted by the HRV analysis and were investigated using genetic algorithms with three different subject selection methods and five different machine learning classifiers. Results: Three parameters: meanRR, alpha1, and sd2/sd1 were considered significant, combining the results obtained by the genetic algorithm. Finally, machine learning classifications were performed by training classifiers with only those three features. The best result was achieved by the binary Decision Tree classifier, achieving accuracy of 82%, specificity (or precision) of 86%, and sensitivity of 79%. Conclusions: The study’s results highlight the ability to use HRV parameters extraction from PPG signals, combined with genetic algorithms and machine learning classifiers, to determine which features are most helpful in discriminating between healthy and mild-severity COVID-19-affected subjects. Full article

Blood vessels transport blood and deliver essential molecules to cells. In cancer, the tumour vasculature evolves very differently from healthy tissue, not only in morphology but also in functionality. Comprehensive 3D in vivo imaging of the tumour microcirculatory system thus might lead to a clearer understanding of the vascular role in tumour growth and response to cancer therapy. Here, we employed two optical coherence tomography (OCT) extensions, speckle-variance and Doppler, to study the microvascular architecture and blood flow in normal murine and xenograft tumour tissue. We explored the biophysics of blood flow in microcirculation and extracted relevant quantification features such as vessel diameters and velocity histograms, and combined diameter–velocity plots. It was demonstrated that tumour microcirculation evolves in time and differs from healthy tissue, impacting tumour growth kinetics. This proof-of-principle study demonstrates the potential of OCT to provide an understanding of the temporal evolution of the tumour vasculature and its relationship with tumour development. Full article

Atherosclerosis is an autoimmune disease characterized by lipid imbalances and chronic inflammation within blood vessels, with limited preventive and treatment options currently available. In this study, a vaccine prepared with COL6A6 peptide (named the Pep_A6 vaccine) was administered to immunize Apoe^−/− mice, and the immune mechanism of the Pep_A6 vaccine against atherosclerosis was first investigated. The results of arterial oil red O staining demonstrated that the Pep_A6 vaccine significantly reduced the atherosclerotic plaque area in Apoe^−/− mice fed with a high-fat diet for 20 weeks. A flow cytometry analysis revealed that the Pep_A6 vaccine inhibited Th1 cell differentiation and increased the proportion of Treg cells. Furthermore, there was a significant increase in Ly6C^low monocytes observed in the vaccinated group. The ELISA results showed that the Pep_A6 vaccine induced a significant expression of Pep_A6-specific antibody IgG and IgG1 in mouse serum. Additionally, we found that the Pep_A6 vaccine significantly decreased serum LDL-C content and regulated the expression of genes related to liver lipid metabolism. Together, our findings suggest that the Pep_A6 vaccine alleviates atherosclerosis by inducing a positive immune response and regulating lipid metabolism, providing new insights into potential prevention strategies for atherosclerosis as an innovative vaccine. Full article

Pericytes are versatile cells integral to the blood vessel walls of the microcirculation, where they exhibit specific stem cell traits. They are essential in modulating blood flow, ensuring vascular permeability, and maintaining homeostasis and are involved in the tissue repair process. The human endometrium is a unique and complex tissue that serves as a natural scar-free healing model with its cyclical repair and regeneration process every month. The regulation of pericytes has gained increasing attention due to their involvement in various physiological and pathological processes. However, endometrial pericytes are less well studied compared to the pericytes in other organs. This review aims to provide a comprehensive overview of endometrial pericytes, with a focus on elucidating their physiological function and potential implications in uterine disorders. Full article

Autoimmune thyroid disease (AIT) is the most frequently linked autoimmune condition to type 1 diabetes (T1D). The analysis of immune profiles could provide valuable insights into the study of these diseases. This knowledge could play a crucial role in understanding the relationship between immune profiles and microcirculation structures and functions. The present study aimed to test the hypothesis that cytokine levels in T1D patients without and those with comorbid Hashimoto’s disease differ significantly. The total study group (total T1D) consisted of 62 diabetic young patients: 43 T1D and 19 T1D + AIT matched for age, age at onset, and duration of diabetes. The control group consisted of 32 healthy young subjects. The levels of cytokines (including TNF-α, IL-35, IL-4, IL-10, IL-18, IL-12, VEGF, and angiogenin) were quantified throughout this investigation. A comparative assessment of the cytokines profiles between the control group and total T1D revealed a statistically significant elevation in the levels of IL-4, TNF-α, IL-18, VEGF, and angiogenin, accompanied by a notable decline in IL-10. However, IL-35 and IL-12 exhibited comparable levels between the two groups. A comparison of cytokine levels between T1D + AIT and T1D groups revealed that only angiogenin levels were statistically significantly higher in T1D + AIT. The results of our study indicated that the alterations in cytokine levels associated with AIT did not correspond to the observed changes in T1D-related outcomes. The sole notable observation was the elevation of angiogenin expression, an angiogenic factor. Full article

Background: Free muscle flaps can develop significant postoperative edema and wound exudation, thereby increasing interstitial pressure and potentially compromising microcirculation. While concerns exist regarding negative pressure wound therapy (NPWT) to compress free flaps and hinder monitoring, recent studies have indicated a reduction in edema and an increase in blood flow. Objective: To compare microcirculation in free latissimus dorsi muscle (LDM) flaps dressed with and without NPWT. Methods: This retrospective cohort study analyzed prospectively collected data of patients who received free LDM flap reconstruction. Patients were separated into two groups according to management with or without NPWT. Microcirculation was evaluated continuously for up to 72 h utilizing laser doppler flowmetry and tissue spectrometry. Results: In total, n = 61 patients (26 females, 35 males) with an average age of 56.90 (17.4) years were included. NPWT was applied in 12 patients, while a regular cotton dressing was used in 49 patients. Overall, no significant differences in the number of minor and major complications were observed between groups. Both groups showed an increase in microvascular flow over the investigated time period. The flow showed higher absolute values in the NPWT group, reaching statistical significance at 12 h post-anastomosis, p = 0.038. There was a tendency for lower rHb values in the NPWT group, without reaching statistical significance. Conclusions: The presented study confirms the increase in microvascular flow after NPWT application. Whilst ensuring continuous free flap monitoring utilizing laser doppler flowmetry and spectrometry, the data further support the safety of NPWT application without risking vascular compromise due to external compression. Full article