Clinical Hemorheology and Microcirculation - Volume 82, issue 2

Authors: Zhang, Pu | Wang, Weiping | Li, Meilan

Article Type: Research Article

Abstract: BACKGROUND: Dysfunction of endothelial cells in the arterial vasculature is an essential contributor to the pathogenesis of atherosclerosis. Circular RNAs (circRNAs) exert important regulatory functions in endothelial cell dysfunction. Here, we explored the precise role and mechanism of circ_0050486 in regulating endothelial cell injury induced by oxidized low-density lipoprotein (ox-LDL). METHODS: Circ_0050486, microRNA (miR)-182-5p and myeloid differentiation primary response gene 88 (MyD88) were quantified by quantitative real-time PCR or western blot. Cell viability, proliferation and apoptosis were examined by MTS, 5-Ethynyl-2’-Deoxyuridine (EdU), and flow cytometry assays, respectively. Direct relationship between miR-182-5p and circ_0050486 or MYD88 was verified by …dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: Circ_0050486 was upregulated in atherosclerosis serum and ox-LDL-treated human aortic endothelial cells (HAECs). Silencing of circ_0050486 suppressed HAEC injury induced by ox-LDL. Mechanistically, circ_0050486 targeted miR-182-5p, and the effects of circ_0050486 silencing were partially due to the upregulation of miR-182-5p. MYD88 was a direct target of miR-182-5p, and miR-182-5p-mediated inhibition of MYD88 attenuated ox-LDL-evoked HAEC injury. Circ_0050486 bound to miR-182-5p to regulate MYD88 expression. Additionally, the NF-κB signaling pathway was involved in the regulation of circ_0050486/miR-182-5p/MYD88 axis in ox-LDL-treated HAECs. CONCLUSION: Our study identifies the functional role of circ_0050486 in ox-LDL-induced endogenous cell injury and establishes a mechanism of circ_0050486 function by affecting MYD88 through competitively binding to shared miR-182-5p. Show more

Keywords: Atherosclerosis, endogenous cells, circ_0050486, miR-182-5p, MYD88

DOI: 10.3233/CH-211259

Citation: Clinical Hemorheology and Microcirculation, vol. 82, no. 2, pp. 107-124, 2022

Authors: Hecko, Sophie | Lutze, Stine | Arnold, Andreas | Haase, Hermann | Jünger, Michael | Riebe, Helene

Article Type: Research Article

Abstract: BACKGROUND: Edema and subjective leg complaints (e.g. pain, heaviness) after long standing or sitting, are defined as orthostatic leg complaints or occupational edema. Compression hosiery should help to prevent or decrease those symptoms. OBJECTIVE: Assess the effects on leg discomforts and leg volume and wearing comfort in two medical below-knee compression stocking types (A vs. B) with an interface pressure of 18 –20 mmHg and a below-knee-low-pressure support stocking (LPSS) with an interface pressure of 8–10mmHg (C). METHODS: Two different types of below-knee medical compression stockings and a LPSS were examined in this randomized, blinded, crossover …trial in volunteers having leg discomforts and edema after being in an upright position during the day. Participants were divided into two cohorts, and each type of stocking was worn for three consecutive days in one week with a subsequent washout phase. The assessment of effects and wearing comfort was ascertained by questionnaires. Volume changes in the lower leg were measured with the Bodytronic 600® (Bauerfeind AG, Zeulenroda, Germany). RESULTS: A significant reduction of lower leg volume (mean stocking A: 204.7 ml; mean stocking B: 153.5 ml; mean stocking C: 48.2 ml) and a significant reduction of the life-quality dimension leg-complaints (p  < 0.0001) was achieved by all three types of stockings. Compared to the LPSS both compression stockings decreased the lower leg volume significantly more (p  < 0.001) and had a significant better fit (p  < 0.001). CONCLUSION: Below-knee medical compression stockings with an interface pressure 18–21mmHg and LPSS with an interface pressure of 8–10 mmHg reduce significantly occupational orthostatic edema and leg discomforts which are due to long standing and sitting activities. Show more

Keywords: Occupational leg edema, wear comfort, quality of life, compression therapy, leg discomfort

DOI: 10.3233/CH-211366

Citation: Clinical Hemorheology and Microcirculation, vol. 82, no. 2, pp. 125-139, 2022

Authors: Chebotareva, Natalia | Berns, Angelina | McDonnell, Valerie | Sovetnikov, Egor | Berns, Svetlana | Guliaev, Sergey | Solonkina, Alena

Article Type: Research Article

Abstract: Nephrotic syndrome (NS) is associated with a high risk for venous and arterial thrombosis due to hypercoagulability. Integral tests designed to assess hemostasis can become an alternative for measuring hypercoagulability in patients with NS. STUDY OBJECTIVE: To assess hemostatic disorders in CGN patients complicated by NS using the thrombodynamics test. MATERIALS AND METHODS: The study included 60 adult patients with chronic glomerulonephritis (CGN), mean age 37 years, 31 (52%) women, and 29 (48%) men. Among all patients, 53 % of patients had NS, 47 % had no sign of NS. Hemostasis was assessed using the thrombodynamics test. …The results were compared with biochemical parameters, which are usually associated with NS and renal dysfunction. RESULTS: According to the thrombodynamics test, CGN patients with NS demonstrated a tendency to hypercoagulability: increased rates of V (rate of clot growth), increased D (clot density), and increased CS (clot size) after 30 minutes. A positive correlation of these parameters with the serum albumin, creatinine levels, and glomerular filtration rate (GFR) indicates the influence of severe NS and renal dysfunction on the hemostasis activation in CGN patients with NS. CONCLUSION: According to the thrombodynamics test, CGN patients with NS demonstrate increased rates of clot formation, increased clot size after 30 minutes, and increased clot density due to secondary hemostasis activation. These changes positively correlate with the severity of hypoalbuminemia, hypercholesterolemia, and renal dysfunction in NS patients. Show more

Keywords: Blood coagulation, nephrotic syndrome, thrombodynamics, hypercoagulation

DOI: 10.3233/CH-221391

Citation: Clinical Hemorheology and Microcirculation, vol. 82, no. 2, pp. 141-148, 2022

Authors: Shaik, Aleesha | Chen, Qinzhong | Mar, Phyu | Kim, HyoungSup | Mejia, Priscilla | Pacheco, Hannah | Goonewardena, Sascha N. | Cho, Daniel J. | Rosenson, Robert S.

Article Type: Research Article

Abstract: BACKGROUND: Elevated estimated blood viscosity (EBV), derived from hematocrit and globulins, is associated with thrombotic complications, organ failure, and higher mortality in COVID-19 patients. Although informative, EBV does not account for cellular interactions or fibrinogen. OBJECTIVE: Investigate whether patients with acute and recent COVID-19 have altered whole blood viscosity (WBV) when measured at both high and low shear rates using in vitro blood samples from patients. METHODS: Cross-sectional study of 58 patients: 15 in the intensive care unit with acute COVID-19, 32 convalescent (9 < 8weeks [W] from acute infection, 23 > 8 W), and 11 controls without COVID-19. WBV was …measured at high (300 s–1 ) and low (5 s–1 ) shear rates (HSR, LSR) using a scanning capillary viscometer. RESULTS Acute and convalescent patients < 8 W had mean WBV at LSR (16.0 centipoise [cP] and 15.1 cP) and HSR (5.1 cP and 4.7 cP). Mean WBV of convalescent > 8 W and control patients were 12.3 cP and 13.0 cP at LSR, and 4.1 cP and 4.2 cP at HSR. Acute and < 8 W patients had significantly higher WBV at both HSR and LSR compared to patients > 8 W (all p≤0.01). No significant differences in WBV were observed between acute and < 8 W patients, or between patients > 8 W and controls. CONCLUSIONS: Hyperviscosity provides a possible explanation for thrombotic risk in acute and convalescent (< 8 W) patients. These findings have important implications for thromboprophylaxis. Show more

Keywords: Anticoagulation, blood viscosity, COVID-19, convalescent, thrombosis

DOI: 10.3233/CH-221429

Citation: Clinical Hemorheology and Microcirculation, vol. 82, no. 2, pp. 149-155, 2022

Authors: Shi, Xian-Quan | Dong, Yunyun | Tan, Xiaoqu | Yang, Peipei | Wang, Chunmei | Feng, Wei | Lin, Yuxuan | Qian, Linxue

Article Type: Research Article

Abstract: OBJECTIVE: This study was performed to investigate the accuracy of conventional ultrasound (US), contrast-enhanced US (CEUS), and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the size of breast cancer. METHODS: In total, 49 breast cancer lesions of 48 patients were included in this study. The inclusion criteria were the performance of total mastectomy or breast-conserving surgery for treatment of breast cancer in our hospital from January 2017 to December 2020 with complete pathological results, as well as the performance of conventional US, CEUS, and DCE-MRI examinations with complete results. The exclusion criteria were non-mass breast cancer shown …on conventional US or DCE-MRI, including that found on CEUS with no boundary with surrounding tissues and no confirmed tumor scope; a tumor too large to be completely displayed in the US section, thus affecting the measurement results; the presence of two nodules in the same breast that were too close to each other to be distinguished by any of the three imaging methods; and treatment with preoperative chemotherapy. Preoperative conventional US, CEUS, and DCE-MRI examinations were performed. The postoperative pathological results were taken as the gold standard. The lesion size was represented by its maximum diameter. The accuracy, overestimation, and underestimation rates of conventional US, CEUS, and DCE-MRI were compared. RESULTS: The maximum lesion diameter on US, CEUS, DCE-MRI and pathology were 1.62±0.63 cm (range, 0.6–3.5 cm), 2.05±0.75 cm (range, 1.0–4.0 cm), 1.99±0.74 cm (range, 0.7–4.2 cm) and 1.92±0.83 cm (range, 0.5–4.0 cm), respectively. The lesion size on US was significantly smaller than that of postoperative pathological tissue (P  < 0.05). However, there was no significant difference between the CEUS or DCE-MRI results and the pathological results. The underestimation rate of conventional US (55.1%, 27/49) was significantly higher than that of CEUS (20.4%, 10/49) and DCE-MRI (24.5%, 12/49) (P  < 0.001 and P  = 0.002, respectively). There was no significant difference in the accuracy of CEUS (36.7%, 18/49) and DCE-MRI (34.7%, 17/49) compared with conventional US (26.5%, 13/49); however, the accuracy of both groups tended to be higher than that of conventional US. The overestimation rate of CEUS (42.9%, 21/49) and DCE-MRI (40.8%, 20/49) was significantly higher than that of conventional US (18.4%, 9/49) (P  = 0.001 and P  = 0.015, respectively). CONCLUSIONS: CEUS and DCE-MRI show similar performance when evaluating the size of breast cancer. However, CEUS is more convenient, has a shorter operation time, and has fewer restrictions on its use. Notably, conventional US is more prone to underestimate the size of lesions, whereas CEUS and DCE-MRI are more prone to overestimate the size. Show more

Keywords: Ultrasound, contrast-enhanced ultrasound, dynamic contrast-enhanced magnetic resonance imaging, breast, breast cancer

DOI: 10.3233/CH-221456

Citation: Clinical Hemorheology and Microcirculation, vol. 82, no. 2, pp. 157-168, 2022

Authors: Wang, Yisheng | Pei, Wen | Lu, Ping

Article Type: Research Article

Abstract: BACKGROUND: Circular RNA (circRNA) is considered to be an important regulator of human diseases, including atherosclerosis (AS). However, the role of circ_ARHGAP32 in AS formation needs further confirmation. OBJECTIVE: To explore the role of circ_ARHGAP32 in AS formation. METHODS: Oxidized low density lipoprotein (ox-LDL) was used to treat vascular smooth muscle cells (VSMCs) to mimic AS cell models in vitro . The expression of circ_ARHGAP32, microRNA (miR)-665, and fibroblast growth factor 2 (FGF2) was analyzed by quantitative real-time PCR. VSMCs function was measured by EdU assay, cell counting kit 8 assay and transwell assay. Protein expression …was determined using western blot analysis. Dual-luciferase reporter assay and RNA pull-down assay were performed to verify RNA interaction. RESULTS: Circ_ARHGAP32 was highly expressed in AS patients and ox-LDL-induced VSMCs. Knockdown of circ_ARHGAP32 repressed ox-LDL-induced proliferation and migration in VSMCs. Circ_ARHGAP32 sponged miR-665 to positively regulate FGF2. MiR-665 inhibitor reversed the regulation of sh-circ_ARHGAP32 on ox-LDL-induced VSMCs proliferation and migration. MiR-665 also had a suppressive effect on the proliferation and migration of ox-LDL-induced VSMCs, and this effect could be reversed by FGF2 overexpression. CONCLUSIONS: Circ_ARHGAP32 might be a potential target for AS treatment, which promoted ox-LDL-induced VSMCs proliferation and migration by regulating miR-665/FGF2 network. Show more

Keywords: Atherosclerosis, circ_ARHGAP32, miR-665, FGF2

DOI: 10.3233/CH-221469

Citation: Clinical Hemorheology and Microcirculation, vol. 82, no. 2, pp. 169-182, 2022

Authors: Watson, Oliver | Pillai, Suresh | Howard, Matthew | Zaldua, Jun-Cezar | Whitley, Janet | Burgess, Brian | Lawrence, Matthew | Hawkins, Karl | Morris, Keith | Evans, Phillip Adrian

Article Type: Research Article

Abstract: BACKGROUND: A significant degree of mortality and morbidity in Covid-19 is due to thromboembolic disease. Coagulopathy has been well described in critically unwell patients on ICU. There is less clear evidence regarding these changes at the time of presentation to the Emergency Department and the progression of disease over time. OBJECTIVE: We sought to investigate whether coagulation markers can predict severity and how they change over the disease course. METHODS: Patients presenting to a single University Teaching Hospital were recruited and followed up if PCR was positive. Alongside routine blood testing, Rotational Thromboelastometry (ROTEM) was performed. …Outcome data was recorded for all patients, and ROTEM values were compared across outcome groups. RESULTS: Extem and Intem Maximum Lysis were significantly reduced in those who died or required an ICU admission, indicating a reduced ability to break down clot mass in the most critically unwell patients. CONCLUSION: Comparisons between groups demonstrated that one distinguishing feature between those who require ICU admission or die of Covid-19 compared with those who survive a hospital stay to discharge was the extent to which fibrinolysis could occur. Mortality and morbidity in Covid-19 infection appears in part driven by an inability to break down clot mass. Show more

Keywords: Covid-19, Coagulopathy, ROTEM, Visco-elastic testing

DOI: 10.3233/CH-221491

Citation: Clinical Hemorheology and Microcirculation, vol. 82, no. 2, pp. 183-191, 2022

Authors: George, Ashna | Deepika, Chenna | Mohan, Ganesh | Srishail, Riya | Rajendran, Vinu | Shastry, Shamee | Balakrishnan, Jayaraj Mymbilli | Rao, Shwethapriya

Article Type: Research Article

Abstract: BACKGROUND: The assessment of ADAMTS13 factor activity and inhibitor levels was conducted in severe COVID-19 patients as an observational study. RESULTS: A total of 14 patients were included and the average ADAMTS13 activity level at the time of admission was 28.54±30.74% (range 1.83–86.67%) which was reduced compared to controls (88.09±14.77). Nine patients had reduced ADAMTS13 factor activity (<40%) and 77.7% among them had severe deficiency (<10% activity). ADAMTS13 inhibitor was positive (>15 IU/mL) only in two patients and an overall mean value was 8.15±5.8. Elevated D-Dimer and length of hospital stay had significant correlation with ADAMTS13 activity (–0.247 …and 0.306 respectively). No features of thrombotic microangiopathy were observed and hence no plasma exchange was performed. CONCLUSION: Reduced ADAMTS13 factor activity without inhibitor development may give a clue to the disease progress in COVID-19. Show more

Keywords: ADAMTS13, Inhibitors, COVID-19, Coagulopathy, SARS CoV2

DOI: 10.3233/CH-221514

Citation: Clinical Hemorheology and Microcirculation, vol. 82, no. 2, pp. 193-198, 2022