Clinical Hemorheology and Microcirculation - Volume Pre-press, issue Pre-press

Authors: Liu, Fang | Gao, Bo | Wang, Yu

Article Type: Research Article

Abstract: BACKGROUND: Atherosclerosis (AS) is a common inflammatory cardiovascular disease, and circular RNAs (circRNAs) are associated with the pathogenesis of AS. CircRNA Interleukin (IL)-1 receptor-associated kinase 1 (circIRAK1, hsa_circ_0091822) was upregulated in AS. The aims of this study were to ascertain the function and mechanism of circIRAK1 in AS. METHODS: Human Umbilical Vein Endothelial Cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL). RNA expression was detected by reverse transcription-quantitative polymerase chain reaction assay. Cell viability was examined using Cell Counting Kit-8 assay. Tube formation ability was measured by tube formation assay. Cell apoptosis was assessed using flow cytometry. …Western blot was used for protein detection. Inflammatory reaction was evaluated via Enzyme-linked immunosorbent assay. Oxidative injury was analyzed by commercial kits. Target binding was determined through dual-luciferase reporter assay, RNA immunoprecipitation assay and pull-down assay. RESULTS: The expression of circIRAK1 was upregulated in AS serums and ox-LDL-treated HUVECs. Silencing circIRAK1 enhanced cell viability and angiogenesis while suppressed cell apoptosis, inflammatory response and oxidative stress in ox-LDL-stimulated HUVECs. CircIRAK1 served as a molecular sponge for miR-330-5p. CircIRAK1 regulated ox-LDL-mediated cell injury by absorbing miR-330-5p. In addition, miR-330-5p prevented endothelial cell dysfunction caused by ox-LDL via targeting tripartite motif containing 14 (TRIM14). TRIM14 expression was upregulated by circIRAK1 through sponging miR-330-5p. CONCLUSION: These results suggested that circIRAK1 upregulated TRIM14 by interacting with miR-330-5p, consequently contributing to ox-LDL-induced endothelial cell injury in AS. Show more

Keywords: circIRAK1, atherosclerosis, miR-330-5p, TRIM14

DOI: 10.3233/CH-221551

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2022

Authors: Wei, Wenbo | Tang, Min | Wang, Qi | Li, Xiaoming

Article Type: Research Article

Abstract: BACKGROUND: Coronary artery disease (CAD) is a common coronary artery disease. The functional mechanism of circular RNA (circRNA) HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2 (circ_HECW2, hsa_circ_0057583) in ox-LDL-treated human cardiac microvascular endothelial cells (hCMECs) is still unclear. METHODS: Expression levels of circ_HECW2, microRNA (miR)-942-5p, and toll-like receptor 4 (TLR4) were analyzed by quantitative real-time PCR (qRT-PCR) and western blot assays. Cell proliferation and apoptosis were analyzed by 5-ethynyl-2’-deoxyuridine (EdU) assay, cell counting kit-8 (CCK8) assay, and flow cytometry, respectively. Tube formation assay was performed to analyze the angiogenesis of cells. Luciferase reporter and …RNA pull-down assays were performed to analyze the target relationship among circ_HECW2, miR-942-5p and TLR4. RESULTS: Circ_HECW2 and TLR4 expression levels were up-regulated and miR-942-5p expression was decreased in the serum of CAD patients and oxidized low-density lipoprotein (ox-LDL)-induced hCMECs. Knockdown of circ_HECW2 enhanced cell proliferation and inhibited cell apoptosis in ox-LDL-treated hCMECs. MiR-942-5p was the target of circ_HECW2 and directly targeted TLR4. Moreover, the effect of circ_HECW2 knockdown could be weakened by anti-miR-942-5p, and TLR4 could restore the function of miR-942-5p on cell damage of ox-LDL-induced hCMECs. CONCLUSION: Circ_HECW2 could regulate ox-LDL-induced cardiovascular endothelial cell dysfunction through targeting miR-942-5p/TLR4 axis. Show more

Keywords: Circ_HECW2, miR-942-5p, TLR4, coronary artery disease

DOI: 10.3233/CH-221550

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2022

Authors: Chen, Jie | Zhang, Bo

Article Type: Research Article

Abstract: Hereditary hemorrhagic telangiectasis (HHT) is an autosomal dominant hereditary disease, which can lead to abnormal angiogenesis. We performed contrast-enhanced ultrasound (CEUS) in a patient with HHT represented with hemothorax. After targeted embolization, the condition of hemothorax improved. In this case, we explore the use of CEUS to locate the responsible vessel of hemothorax, and found that CEUS could be used as a complementary preoperative method of localization with Computed tomography angiography (CTA).

Keywords: Contrast-enhanced ultrasound, hereditary hemorrhagic telangiectasis, hemothorax

DOI: 10.3233/CH-221646

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-6, 2022

Authors: Chen, Wanjiao | Hu, Bin | Zhang, Shuya | Zheng, Ying | Zhou, Zhong | Mai, Yifeng

Article Type: Research Article

Abstract: BACKGROUND: Accumulating evidence shows that the increase in blood viscosity (BV) is an independent risk factor for atherosclerosis and its related diseases, but as far as we know, there are few studies on the relationship between blood viscosity and carotid plaque severity. Therefore, we aimed to investigate the relationship between blood viscosity and the presence of carotid plaques, and further explore its relationship with the severity of carotid plaques. METHODS: We retrospectively analyzed the data of consecutive subjects in the physical examination center of the Affiliated Hospital of Ningbo University Medical College from January 2022 to May 2022. …The parameters of blood viscosity include the whole blood viscosity (WBV) at high, middle, and low shear rate, plasma viscosity (PV), hematocrit (HCT), rigidity “k”, rigidity index (RI), aggregation index (AI) and electrophoresis rate (ER), and standardized BV calculated by Quemada’s equation were included in the study. Carotid plaque score (CPS) was used to measure the severity of carotid artery disease, and participants were divided into mild, moderate, and severe groups according to the quartile of the score. Independent samples t -test and one-way ANOVA were used to compare normally distributed continuous variables between two or more independent groups, respectively. Binary logistic regression was used to evaluate the risk factors of carotid plaque. RESULTS: 314 men were enrolled in the study, of which 165 participants were diagnosed with Carotid artery plaque (CAP) (66.9%). Compared with the CAP- group, the WBV and PV of the CAP+group decreased, but the difference only existed in the PV (p  = 0.001). However, standardized BV values (HCT set at 0.45) were higher in the CAP+group than in the CAP- group (3.8643±0.35431vs 3.9542±0.64871, p  = 0.188). Regarding the rigidity and aggregation of RBC, the parameters including rigidity “k”, RI, AI and ER increased in the CAP+group compared with the CAP- group. The difference was statistically significant in k and ER (p  = 0.04, p  = 0.009). To assess the severity of carotid plaque, we divided the participants into mild, moderate, and severe groups by using the tertile of CPS value. The mild group was defined as CPS≤0.5 (n  = 108), the moderate group as 0.5 <  CPS≤1.7 (n  = 105), and the severe group as CPS >  1.7 (n  = 101). It was found that WBV and PV decreased with the increase of plaque severity, but the difference among the three groups was significant in PV (F  = 8.073, p  <  0.0001). In addition, with the severity of plaque from mild to severe, standardized BV gradually increased, which were 3.8611±0.34845, 3.8757±0.36637, 3.9007±0.38353 respectively. The difference between the groups was close to statistically significant (F  = 2.438, p  = 0.089). The values of parameters describing erythrocyte aggregation and rigidity increased among the mild, moderate, and severe groups. The difference was statistically significant in RBC rigidity “k” and ER of RBC (F  = 3.863, p  = 0.022; F  = 5.897, p  = 0.003, respectively). CONCLUSION: Increased blood viscosity is a risk factor for carotid plaque, but its increase may be hidden by decreased hematocrit. Therefore, it is necessary to comprehensively analyze various parameters of blood viscosity, such as the standardized BV calculated by Quemada’s equation, which may provide more useful reference value. Show more

Keywords: Carotid plaque, blood viscosity, hematocrit, Quemada’s equation

DOI: 10.3233/CH-221597

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2022

Authors: Shafie, Neda | Kordi, Negin | Gadruni, Keivan | SalehFard, Ziba | Jung, Friedrich | Heidari, Naser

Article Type: Research Article

Abstract: BACKGROUND: Physical training in patients with heart failure can affect hemodynamic, cardiac and angiogenesis parameters. OBJECTIVE: The aim of the present study was to investigate the effects of traditional moderate-intensity rehabilitation training and interval training on some angiogenesis factors in coronary artery bypass graft (CABG) patients. METHODS: Thirty CABG patients (mean age±SD, 55±3 years) were randomly assigned to one of three groups: high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) or the control group. After the initial assessments, eligible patients in the experimental groups (HIIT and MICT) performed exercise training for 8 weeks, while the …control group did not. Angiogenesis and angiostatic indices, including pro-adrenomedullin (pro-ADM), basic fibroblast growth factor (bFGF), and endostatin, were then measured. RESULTS: The results showed no significant difference between pro-ADM in the HIIT and MICT groups (P  = 0.99), but a significant difference was found between MICT and the control group and between HIIT and the control group (P  = 0.001). There is also no significant difference between the bFGF levels in the HIIT and MICT training groups (P  = 1.00), but the changes in this factor between the training groups and the control group were significant (P  = 0.001). There was a significant difference between the levels of endostatin in all three groups. CONCLUSIONS: Two methods of cardiac rehabilitation (HIIT and MICT) may be useful for the recovery of patients with coronary artery bypass grafting. This improvement manifested itself in changes in angiogenesis and angiostatic indices in this study. However, more extensive studies are needed to investigate the effects of these two types of rehabilitation programs on other indicators of angiogenesis and angiostatic. Show more

Keywords: Training, angiogenesis, cardiovascular, endostatin, pro-adrenomedullin

DOI: 10.3233/CH-221605

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2022

Authors: Toprak, Kenan | Kaplangoray, Mustafa | Palice, Ali | İnanır, Mehmet | Memioğlu, Tolga | Kök, Zafer | Altıparmak, İbrahim Halil | Toprak, İbrahim Halil | Biçer, Asuman | Demirbağ, Recep

Article Type: Research Article

Abstract: BACKGROUND: Complete atrioventricular block is most commonly caused by age-related degeneration and fibrosis in the cardiac conduction system and is called primary idiopathic complete atrioventricular (iCAVB). Although many factors affect this situation, which increases with age in the cardiac conduction system, the relationship between whole blood viscosity (WBV) and iCAVB has not been clarified until now. In this study, we aim to reveal the relationship between iCAVB and WBV. METHODS AND RESULTS: 141 patients with dual-chamber permanent pacemaker implanted for iCAVB and 140 age- and sex-matched subjects were included in this study. The WBV values of the study …groups were compared in both high shear rate (HSR) and low shear rate (LSR). Both WBV at HSR and WBV at LSR were significantly higher in the iCAVB group compared to the control group (16.11 [15.14–16.89] vs 14.40 [13.62–15.58]; 39.82 [17.43–55.23] vs 1.38 [–13.14–26.73]; p  <  0.001, respectively). The patient population was followed up for an median of 38 months for all-cause mortality. Higher mortality rates were found in higher WBV at HSR and WBV at LSR (p  <  0.001,for both). CONCLUSIONS: In this study, WBV was found to be an independent predictor for iCAVB, and in these patients WBV was associated with poor clinical outcomes. Show more

Keywords: Primary idiopathic complete atrioventricular block, whole blood viscosity, high shear rate, low shear rate

DOI: 10.3233/CH-221596

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2023

Authors: Qiu, Yi-Jie | Cheng, Juan | Zuo, Dan | Zhang, Qi | Tian, Xiao-Fan | Lu, Xiu-Yun | Chen, Sheng | Dong, Yi | Wang, Wen-Ping

Article Type: Research Article

Abstract: OBJECTIVE: To explore the value of vascular architecture detected by micro vascular imaging (MVI) in preoperative diagnosis of focal liver lesions (FLLs). METHODS: In this retrospective study, patients with surgery and histopathologically proved or radiologically confirmed FLLs were included. Vascular architecture of FLLs were acquired by color Doppler flow imaging (CDFI) and MVI on LOGIQ™ E20 ultrasound machine (C1–6 convex array probes). Alder semiquantitative analysis (grade 0–3) and morphologic features of blood vessels (pattern a–f) were used to assess the blood flow within the FLLs. Interobserver agreement for evaluating blood flow of FLLs was analyzed. Using Adler’s grading …or morphologic patterns as diagnostic criteria for malignant FLLs, the diagnostic efficiency was analyzed and compared. RESULTS: From October 2021 and February 2022, 50 patients diagnosed with 40 malignant FLLs and 10 benign FLLs were finally included. The Kappa value within two observers for evaluating the blood flow of FLLs was 0.78 for MVI and 0.55 for CDFI. According to Alder semiquantitative analysis, more high-level blood flow signals (grade 2–3) were detected by MVI than CDFI (P  <  0.05). Based on high-level blood flow signals (grade 2–3) and hypervascular supply patterns (pattern e and f), the diagnostic accuracy for malignant FLLs were 76% and 68% for MVI, 56% and 38% for CDFI, respectively. CONCLUSION: MVI is superior to CDFI in evaluating vascular architecture of FLLs. The high-level flow signals and hypervascular pattern detected by MVI have a useful and complementary value in preoperative non-invasive identification of malignant FLLs. Show more

Keywords: Micro vascular imaging (MVI), color Doppler flow imaging (CDFI), focal liver lesions (FLLs), blood flow, vascular architectures

DOI: 10.3233/CH-221682

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2022

Authors: Huang, Yunlin | Wang, Ying | Liu, Lingxiao | Zhu, Lei | Qiu, Yijie | Zuo, Dan | Lu, Xiuyun | Dong, Yi | Jung, Ernst-Michael | Wang, Wenping

Article Type: Research Article

Abstract: OBJECTIVES: To explore the potential added value of dynamic contrast enhanced ultrasound (DCE-US) using VueBox® software for the diagnosis of small solid thyroid nodules (≤1.0 cm). PATIENTS AND METHODS: This prospective study was approved by the institutional review board and it was performed at two hospitals from January 2020 to October 2020. B mode ultrasound and contrast enhanced ultrasound (CEUS) images were obtained for 79 small solid thyroid nodules (≤1.0 cm) confirmed by ultrasound-guided fine needle aspiration cytology results in 79 consecutive patients (55 women and 24 men, median age: 41 years). The CEUS time-intensity curves (TICs) of thyroid nodules …and surrounding parenchyma were created by VueBox® software (Bracco, Italy). The CEUS quantitative parameters were obtained after curve fitting. The diagnostic efficiency of the diagnostic performance of CEUS and DCE-US was evaluated and compared. The weighted kappa statistic (κ) was performed to assess the interobserver agreement and consistency between the diagnosis of CEUS and DCE-US. RESULTS: Among the 79 thyroid nodules, 56 (70.9 %) were malignant and 23 (29.1 %) were benign lesions. Hypoenhancement during the arterial phase of CEUS was associated with malignancy (P  <  0.001), with an AUC of 0.705 (sensitivity 71.4 %, specificity 69.6 %). Among all CEUS quantitative parameters, the peak enhancement (PE), wash-in rate (WiR), and wash-out rate (WoR) of DCE-US in malignancies were significantly lower than those in benign nodules (P  = 0.049, P  = 0.046, and P  = 0.020, respectively). The AUCs of PE, WiR, and WoR were 0.642 (sensitivity 65.2 %, specificity 67.9 %), 0.643 (sensitivity 43.5 %, specificity 91.1 %), and 0.667 (sensitivity 69.6 %, specificity 69.6 %) in differentiation between benign and malignant small solid thyroid nodules (≤1.0 cm), respectively. Comparing the quantitative parameters of DCE-US between small solid thyroid nodules and surrounding normal thyroid parenchyma, the PE, WiAUC, WiR, WiPI, WoAUC, WiWoAUC, and WoR of the nodules were significantly lower than those of normal thyroid tissue (P  = 0.008, P  <  0.001, P  = 0.037, P  = 0.009, P  = 0.003, P  = 0.002, P  = 0.049, respectively). A total of 16 (20.3 %) nodules showed isoenhancement during the arterial phase of CEUS, while the median PE ratio of surrounding tissue and thyroid nodules was 1.70 (IQR: 1.33–1.89). CONCLUSIONS: VueBox® is a helpful tool for the evaluation of dynamic microvascularization of thyroid nodules, and DCE-US using VueBox® perfusion analysis could provide added values for differential diagnosis of small solid thyroid nodules (≤1.0 cm). Show more

DOI: 10.3233/CH-221681

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2022

Authors: Schleder, Stephan | Jung, Ernst-Michael | Schicho, Andreas | Schreyer, Andreas G. | Habicher, Werner | Grassinger, Jochen | Dollinger, Marco

Article Type: Research Article

Abstract: BACKGROUND: Cervical lymphadenopathy can be benign or malignant. Its accurate diagnosis is necessary to determine appropriate treatment. Ultrasound-guided core needle biopsies (US-CNBs) are frequently used as a percutaneous sampling approach. OBJECTIVES: Our aim was to identify the efficacy and safety of US-CNBs in 125 patients with cervical lymphadenopathy and clinically suspected head and neck cancer during the COVID-19 pandemic with limited surgical resources. METHODS: US-CNBs of pathological lymph nodes were performed in 146 lymph nodes on 125 patients. Biopsies were performed ultrasound-guided with a reusable gun core biopsy system and a 10-cm-long 16-G needle. Standard of …reference for the histological findings were panendoscopy, clinical and sonographic follow-up, surgical biopsy or a repeat US-CNB. RESULTS: Adequate material for histologic diagnosis was obtained in 111 patients (89%), of these 83 patients (75%) were diagnosed as malignant, whereas benign lymphadenopathy accounted for 28 patients (25%). Therefore, US-CNB was able to identify malignant or benign lymphadenopathy with an overall accuracy of 88% and 90%, respectively. CONCLUSIONS: Percutaneous US-CNB is a safe and effective alternative to surgical biopsy in the management of cervical lymphadenopathy in patients with clinically suspected head and neck cancer in a setting with limited resources. Show more

DOI: 10.3233/CH-221680

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2022

Authors: He, Dequan | Li, Zhiliang | Chen, Youquan | Huang, Ming

Article Type: Research Article

Abstract: BACKGROUND: Dysfunction of endothelial cells is now considered a vital contributor to the pathogenesis of atherosclerosis (AS). Moreover, circular RNA (circRNA) circ_0029589 has been found to be involved in the regulation of oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell damage. Nevertheless, its molecular mechanism in ox-LDL-triggered endothelial cell injury is poorly defined. METHODS: Human umbilical vein endothelial cells (HUVECs) treated with ox-LDL were applied as cell models of AS. Circ_0029589, microRNA-1197 (miR-1197), and Ras-related protein Rab-22A (RAB22A) expression were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, angiogenesis, and invasion were detected using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium …bromide (MTT), 5-ethynyl-2’-deoxyuridine (EdU), flow cytometry, tube formation, and transwell assays. Western blot analysis of Cleaved-caspase-3, B-cell lymphoma-2 related X protein (Bax), and RAB22A. IL-6, IL-1β, and Tumor necrosis factor α (TNF-α) levels were gauged using ELISA kits. Superoxide Dismutase (SOD) activity and Malondiahyde (MDA) level were assessed using special kits. Bioinformatics software predicted the binding between miR-1197 and circ_0029589 or RAB22A, which was proved using dual-luciferase reporter and RNA pull-down assays. RESULTS: Circ_0029589 and RAB22A expression were strengthened, and miR-1197 was reduced in ox-LDL-treated HUVECs. Importantly, circ_0029589 silencing ameliorated ox-LDL-triggered HUVEC damage via promoting cell proliferation, tube formation ability, invasion, and repressing cell apoptosis, inflammation, and oxidative stress. Mechanical analysis suggested that circ_0029589 might affect RAB22A content through sponging miR-1197. CONCLUSION: Circ_0090231 might protect against ox-LDL-mediated HUVEC injury via the miR-1197/RAB22A axis, which provides a therapeutic strategy for endothelial cell damage of AS. Show more

Keywords: Circ_0029589, miR-1197, RAB22A, ox-LDL, atherosclerosis

DOI: 10.3233/CH-221657

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-18, 2023