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

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: Li, Wei-Wei | Guo, Ze-Ming | Wang, Bing-Cai | Liu, Qing-Quan | Zhao, Wen-An | Wei, Xiao-Lan

Article Type: Research Article

Abstract: OBJECTIVE: Atherosclerosis is a chronic inflammatory disease of the arteries, and its pathogenesis is related to endothelial dysfunction. It has been found that the protein convertase subtilin/kexin9 type (PCSK9) plays an important role in AS, but its specific mechanism is still unclear. METHODS: In this study, we first cultured human umbilical vein endothelial cells (HUVECs) with 50 or 100μg/ml oxidized low-density lipoprotein (ox-LDL) for 24 hours to establish a coronary atherosclerosis cell model. RESULTS: The results showed that ox-LDL induced HUVEC injury and autophagy and upregulated PCSK9 protein expression in HUVECs in a concentration-dependent …manner. Silencing PCSK9 expression with siRNA inhibited ox-LDL-induced HUVEC endothelial dysfunction, inhibited the release of inflammatory factors, promoted HUVEC proliferation and inhibited apoptosis. In addition, ox-LDL increased the expression of LC3B-I and LC3B-II and decreased the expression of p62. However, these processes are reversed by sh-PCSK9. In addition, sh-PCSK9 can inhibit PI3K, AKT and mTOR phosphorylation and promote autophagy. CONCLUSION: Taken together, our research shows that silencing PCSK9 inhibits the PI3K/ATK/mTOR pathway to activate ox-LDL-induced autophagy in vascular endothelial cells, alleviating endothelial cell injury and inflammation. Show more

Keywords: PCSK9, atherosclerotic coronary, autophagy, endothelial cell, PI3K

DOI: 10.3233/CH-242172

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2024

Authors: Li, Chen | Jia, Yong-Rui | Gou, Qiao | Ju, Zhong-Jian

Article Type: Research Article

Abstract: OBJECTIVE: Our prior research has established that X-ray exposure induces pyroptosis in human umbilical vein endothelial cells (HUVECs), with Cx43 playing a regulatory role in this process. However, the precise mechanism by which Cx43 regulates pyroptosis remains unclear. The objective of this study is to assess the involvement of the calcium signaling pathway in Cx43-mediated regulation of X-ray-induced pyroptosis in HUVECs. METHODS: HUVECs were exposed to 10 Gy X-ray radiation either alone or combined with Cx43 overexpression or knockdown. Calcium ions (Ca2+ ) were stained using Fluo-4/AM and analyzed via flow cytometry and confocal microscopy. Pyroptosis was assessed through …flow cytometry by staining with FLICA (fluorescent-labeled inhibitor of caspase) and propidium iodide (PI). Calcium signaling was inhibited using BAPTA/AM, 2-APB, or nifedipine. Protein expression levels were assessed by western blotting. RESULTS: X-ray irradiation induced an increase in intracellular calcium levels in HUVECs in a dose- and time-dependent manner. The results demonstrated that regulating calcium release with BAPTA/AM, 2-APB, or nifedipine significantly reduced pyroptosis. Also, the overexpression of Cx43 significantly attenuated the increase in intracellular calcium. Conversely, Cx43 knockdown via siRNA significantly increased the intracellular calcium levels. Also, interfering with calcium signaling using BAPTA/AM, 2-APB, or nifedipine reduced the raised pyroptosis levels induced by Cx43 knockdown. CONCLUSION: Individual HUVECs exposed to high-dose X-ray irradiation exhibited an increase in intracellular calcium, leading to pyroptosis. Also, upregulating Cx43 expression reduced the pyroptosis levels by inhibiting intracellular calcium concentration. This study introduces new concepts for identifying targets for the prophylaxis and therapy of radiation-induced damage. Show more

Keywords: Calcium, Connexin43, pyroptosis, x-ray

DOI: 10.3233/CH-242381

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2024

Authors: Zhang, Wei-Bing | Deng, Wen-Fang | He, Bei-Li | Wei, Ying-Ying | Liu, Yu | Chen, Zhe | Xu, Ren-Yan

Article Type: Research Article

Abstract: OBJECTIVES: To investigate the diagnostic value of CEUS combined with C-TIRADS for indeterminate FNA cytological thyroid nodules. METHODS: The clinical data, ultrasonic images, C-TIRADS categories and CEUS images of 192 patients with indeterminate FNA cytological thyroid nodules confirmed by the surgical pathology were analyzed retrospectively. The diagnostic efficacy of CEUS, C-TIRADS and CEUS-TIRADS were calculated. RESULTS: The AUCs of CEUS, C-TIRADS and CEUS-TIRADS were 0.905 (95% CI: 0.862∼0.949), 0.881 (95% CI: 0.825∼0.938) and 0.954 (95% CI: 0.922∼0.986), respectively. The sensitivity, specificity, PPV, NPV, accuracy, LR– and LR+ were 84.7% (116/137), 85.5% (47/55), 93.5% (116/124), …69.1% (47/68), 84.9% (163/192), 0.179, 5.82 and 84.7% (116/137), 83.6% (46/55), 92.8% (116/125), 68.7% (46/67), 84.4% (162/192), 0.183, 5.17, 92.7% (127/137), 89.1% (49/55), 95.5% (127/133), 83.1% (49/59), 91.7% (176/192), 0.082, and 8.50, respectively. Compared with CEUS and C-TIRADS, CEUS-TIRADS had improved the AUC, sensitivity and accuracy (all P  < 0.05). CONCLUSIONS: CEUS and C-TIRADS had high diagnostic values in indeterminate FNA cytological thyroid nodules. CEUS-TIRADS improved AUC, diagnostic sensitivity and accuracy, and helped to distinguish indeterminate FNA cytological nodules. Show more

Keywords: Thyroid nodule, contrast enhanced ultrasound, Chinese thyroid imaging reporting and system

DOI: 10.3233/CH-242363

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2024

Authors: Ma, Yue | Du, Jin | Wang, Xin-Xin | Deng, Tong | Qi, Jia-Li | Cheng, Hong | Li, Lu

Article Type: Research Article

Abstract: OBJECTIVE: In this study, we developed an exercise training protocol for assessing both blood pressure dynamics and mRNA expression levels of purine receptors in various vascular tissues during physical activity. The objective is to assess the impact of exercise training on blood pressure regulation in spontaneously hypertensive rats (SHR) and purine receptors in vascular tissues. METHODS: Wistar Kyoto (WKY) and SHR rats were randomly allocated into sedentary (Sed) and exercise training (ExT) groups. Rats in the Sed groups were allowed unrestricted movement, whereas those in the ExT groups underwent a 16-week regimen of low- to moderate-intensity treadmill exercise. …Throughout the intervention period, blood pressure measurements and body weight recordings were conducted. Additionally, mRNA expressions of purine receptors P2X1, P2Y1, and P2Y2 in renal artery (RA), internal carotid artery (Int), thoracic aorta (Aor), and caudal artery (Cau) tissues were assessed. RESULTS: In the Sed group, body weight of SHR rats was observed to be lower compared to the three other groups. Over the course of the exercise regimen, blood pressure in the ExT group of SHR rats reduced gradually, converging towards levels similar to those observed in WKY rats by the conclusion of the exercise period. Regarding mRNA expression patterns of P2X1 receptors across the four blood vessels, WKY and SHR rats demonstrated similar sequences, consistently displaying the highest expression levels in the Cau. Conversely, mRNA expressions of P2Y1 and P2Y2 receptors exhibited distinct sequences across the four blood vessels in both WKY and SHR rats. Notably, compared to the Sed group of WKY rats, mRNA expression of P2X1 receptor in the Int of SHR rats revealed an increase, while expressions in the Aor of WKY rats and the Cau of SHR rats decreased following exercise. Expression of P2Y1 receptor mRNA decreased across all four types of blood vessels in SHR rats. Post-exercise, P2Y1 receptor mRNA expression increased in the Aor, decreased in the Cau of WKY rats, and increased in the Int and renal artery (RA) of SHR rats. Conversely, expressions of P2Y2 receptor mRNA decreased in the Int and Aor of SHR rats. Except for the Aor of WKY rats, expressions of P2Y2 receptor mRNA increased in the other arteries of both rat types following exercise. CONCLUSION: Differences in the distribution of purine receptor subtypes among distinct arterial segments in both WKY and SHR rats were observed. Exercise training was found to enhance mRNA expression levels of P2Y receptors in these rat models. This finding implies that exercise training might reduce hypertension in SHR rats by bolstering the purinergic relaxation response. Show more

Keywords: Blood vessels, exercise training, purine receptors, spontaneous hypertension rat

DOI: 10.3233/CH-242366

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2024

Authors: Chen, Po-Yu | Huang, Hsing-Hao | Chan, Wing-Sum | Liu, Chih-Min | Wu, Tsung-Ta | Chen, Jyun-Han | Chao, Anne | Tien, Yu-Wen | Chiu, Ching-Tang | Yeh, Yu-Chang

Article Type: Research Article

Abstract: BACKGROUND: Recent studies have shown that dexmedetomidine may improve microcirculation and prevent organ failure. However, most evidence was obtained from experimental animals and patients receiving cardiac surgery with cardiopulmonary bypass. This study aimed to investigate the effect of dexmedetomidine on microcirculation and organ injuries in critically ill general surgical patients. METHODS: In this prospective randomized trial, patients admitted to the surgical intensive care unit after general surgery were enrolled and randomly allocated to the dexmedetomidine or propofol groups. Patients received continuous dexmedetomidine or propofol infusions to meet their requirement of sedation according to their grouping. At each time …point, sublingual microcirculation images were obtained using the incident dark field video microscope. RESULTS: Overall, 60 patients finished the trial and were analyzed. Microcirculation parameters did not differ significantly between two groups. Heart rate at 4 h after ICU admission and mean arterial pressures at 12 h and 24 h after ICU admission were lower in the dexmedetomidine group than in the propofol group. At 24 h, serum aspartate aminotransferase (41 (25–118) vs 86 (34–129) U/L, p  = 0.035) and alanine aminotransferase (50 (26–160) vs 68 (35–172) U/L, p  = 0.019) levels were significantly lower in the dexmedetomidine group than in the propofol group. CONCLUSION: Microcirculation parameters did not differ significantly between the dexmedetomidine and propofol groups. At 24 h after ICU admission, serum liver enzyme levels were lower in patients receiving dexmedetomidine as compared to propofol. Show more

Keywords: Microcirculation, dexmedetomidine, propofol, surgery, critical care

DOI: 10.3233/CH-232093

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2024

Authors: Wang, Fang | Guo, Zhangmei | Yang, Guiqi | Yang, Fan | Zhou, Qi | Lv, Hongbin

Article Type: Research Article

Abstract: PURPOSE: Diabetic retinopathy (DR) is a serious retinal vascular disease that affects many individuals in their prime working years. The present research aimed at whether and how LOC681216 (LNC-216) is involved in retinal vascular dysfunction under diabetic conditions. METHODS: Rat retinal microvascular endothelial cells (RRMECs) treated with high glucose (HG) were used for functional analysis. Gene expression analysis was conducted using the Clariom D Affymetrix platform. The wound healing, transwell, and vascular tube formation assays were used to identify the migration, invasion, and tube formation capability of RRMECs. The dual-luciferase reporter confirmed the binding interaction between miR-143-5p and …LNC-216 or matrix metallopeptidase 2 (MMP2). RESULTS: Lnc-216 was upregulated in RRMECs treated with HG. Lnc-216 knockdown markedly suppressed the tube formation, cell migration, and wound healing of cultured RRMECs under HG conditions. Mechanistically, Lnc-216 acted as a miR-143-5p sponge to affect the biological activity of miR-143-5p, which led to increased expression of matrix metallopeptidase 2 (MMP2). CONCLUSIONS: Lnc-216 attenuates diabetic retinal vascular dysfunction through the miR-143-5p/MMP2 axis, providing a potential therapeutic strategy for DR. Show more

Keywords: Lnc-216, miR-143-5p, microarray, diabetic retinopathy, MMP2

DOI: 10.3233/CH-242163

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2024

Authors: Zhu, Yi-Cheng | Zhou, Li | Zu, Dao-Ming | Deng, Shu-Hao | Zhang, Yuan | Shan, Jun | Shi, Xiu-Rong | Jiang, Quan

Article Type: Research Article

Abstract: BACKGROUND: Mesenteric lymphadenitis (ML) demonstrates a distinctive inclination for the pediatric and adolescent demographic and the diagnosis of ML in young children poses a substantial challenge. OBJECTIVE: This prospective study aimed to assess the diagnostic efficacy of Superb Microvascular Imaging (SMI) and Virtual Touch Tissue Imaging quantification (VTIQ) in distinguishing pediatric mesenteric lymphadentitis. METHODS: We examined 82 mesentric lymph node (MLN) in pediatric patients with mesenteric lymphadentitis and 50 MLN in a healthy group. SMI was utilized to evaluate vascularity within the MLN, while MLN stiffness, quantified as shear wave velocity (SWV) in meters per second …(m/s), was assessed using VTIQ. We compared the diagnostic performance of greyscale Ultrasound, US combined with SMI, US combined with VTIQ, and US combined with both SMI and VTIQ. RESULTS: SMI revealed a significant distinction between mesenteric lymphadentitis and normal MLN (p  <  0.001). MLN affected by mesenteric lymphadentis exhibited increased vascularity (marked vascularity: 13/82, 15.85%) compared to normal MLN (marked vascularity: 1/50, 2.00%). Statistically significant differences were observed in SWV values beween mesenteric lymphadentitis and normal MLN (all p -values <0.001). The mean and minimum SWV values for MLN with mesenteric lymphadentitis were 1.66±0.77 m/s and 1.51±0.53 m/s, respectively. Control group SWV values were approximately three times higher than those in the mesenteric lymphadenitis group. The highest area under the curve values were achieved with the combination of all three modalities (0.837, 95% confidence interval: 0.763– 0.896), followed by US + VTIQ (0.795, 0.716– 0.860), US + SMI (0.753, 0.670– 0.824) and US alone (0.642, 0.554– 0.724). CONCLUSION: SMI and VTIQ offer a promising noninvasive adjunct to grayscale ultrasound for identifying mesenteric lymphadentitis in pediatric patients. Show more

Keywords: Mesenteric lymphadenitis, pediatrics, Elastography, Doppler ultrasound

DOI: 10.3233/CH-242305

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2024

Authors: Zhang, Lei-Guang | Li, Hui-Juan | Liu, Shuai | Liu, Jie-Yun

Article Type: Research Article

Abstract: OBJECTIVE: The aim of this study is to investigate the correlation between the triglyceride-glucose-body mass index (TyG-BMI) and the characteristics of various carotid plaques in middle-aged and elderly patients with acute myocardial infarction (AMI). METHODS: A retrospective study was conducted on 380 patients with AMI hospitalized in the Cardiology Department of Kaifeng Central Hospital. Based on carotid ultrasound results, patients were divided into the following two groups: the stable plaque group and the unstable plaque group. Additionally, a control group comprising 380 healthy individuals visiting the hospital’s physical examination center during the same timeframe was established. Fasting venous …blood samples were collected from all participants to measure blood glucose and triglyceride. The baseline TyG-BMI index was calculated using the formula Ln [fasting triglyceride (mg/dL)×fasting blood glucose (mg/dL)/2]×BMI. The correlation between different plaque groups and the TyG-BMI index was analyzed. RESULTS: The TyG-BMI index was significantly higher in the unstable plaque group compared to the stable plaque group, with values of 252.81±29.99 and 201.92±28.72, respectively (P  = 0.034). Spearman’s correlation analysis showed a positive correlation between the instability of carotid plaques and the TyG-BMI index in patients with AMI (r  = 0.521, P  = 0.003). Logistic regression analysis indicated that the TyG-BMI index was an important risk factor for unstable carotid plaques in patients with AMI (OR = 2.691, 95% CI: 1.169–4.123). CONCLUSION: The findings of this study suggest that an elevated TyG-BMI index significantly increases the risk of unstable carotid plaques in patients with AMI, making it an important risk factor for carotid plaque instability. Show more

Keywords: Atherosclerosis, acute myocardial infarction, carotid artery, TyG-BMI index, unstable plaques

DOI: 10.3233/CH-242354

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2024

Authors: Liu, Jinming | Jiao, Wei | Li, Fang | Xie, Yanan | Meng, Mingjie | Hao, Jie

Article Type: Research Article

Abstract: OBJECTIVE: This study intends to explore the effects of Rosuvastatin on ox-LDL induced platelet activation and its molecular mechanism. METHODS: Platelet aggregation rate was detected by aggregometer. ELISA kit was used to detect the levels of cAMP. Immunofluorescence staining was used to detect the platelet adhesion. The expression levels of platelet surface markers CD62p and PAC-1 were detected by flow cytometry. The protein levels of p-p38, p-IKKa and p-IKKB in platelets were detected by western blot. RESULTS: We found that rosuvastatin significantly inhibited platelet aggregation and increased the level of cAMP in a dose-dependent manner. Immunofluorescence …staining results showed that rosuvastatin could inhibit platelet adhesion. Flow cytometry results showed that rosuvastatin could reduce the expression of platelet activation markers. Western blot results showed that rosuvastatin could down-regulate the expression levels of p-p38, p-IKKa and p-IKKb. CONCLUSION: Our study revealed the rosuvastatin could inhibit the aggregation, adhesion and activation of platelet induced by ox-LDL, its mechanism may be related to inhibition of p38/MAPK signal pathway. Show more

Keywords: Rosuvastatin, platelet, aggregation, adhesion, p38/MAPK

DOI: 10.3233/CH-242359

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2024