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: Deng, Jiayi | Wu, Weihao | Zhang, Zimiao | Ma, Xiaomei | Chen, Congjie | Huang, Yanhong | Lai, Yueyuan | Chen, Liling | Chen, Longtian

Article Type: Research Article

Abstract: OBJECTIVE: The purpose of this research was to examine the relationship between the hemoglobin-to-red blood cell distribution width ratio (HRR) and cardiovascular disease (CVD)-related mortality in people who have diabetes. METHODS: Data derived from the National Health and Nutrition Examination Survey (NHANES), between the years 1999 to 2018, were meticulously analyzed. Mortality data, encompassing events until December 31, 2019, were systematically collected. A comprehensive group comprising of 8,732 participants were subjected to scrutiny, and subsequently, classified into four distinct groups predicated upon quartiles of baseline HRR levels: Q1 (n  = 2,183), Q2 (n  = 2,181), Q3 (n  = 2,185), and Q4 …(n  = 2,183). The correlation between HRR and CVD-related mortality was examined through the use of survival curves and Cox proportional hazard regression models, the latter incorporating weights as advised by NHANES. RESULTS: Among the 8,732 participants in the study cohort, CVD-related mortality was identified in 710 cases. The Kaplan-Meier analysis demonstrated a significant association, indicating that a decreased HRR was correlated with a reduction in survival in cases with CVD. Both univariate and multivariable Cox proportional hazard regression analyses consistently indicated that patients exhibiting a lower HRR exhibited a markedly elevated risk of CVD-related mortality in comparison to those with higher HRR. Notably, the correlation between HRR and decreasing CVD-related mortality was discerned to be non-linear. CONCLUSION: In patients with diabetes, a decreased HRR was associated with an increased risk of CVD-related mortality. Show more

Keywords: Cardiovascular disease-related mortality, diabetes mellitus, hemoglobin, NHANES, Red cell distribution width

DOI: 10.3233/CH-242209

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

Authors: Carallo, Claudio | Destito, Michela | Zaffino, Paolo | Caglioti, Chiara | Silipo, Vittorio | De Masi, Paolo Maria | Gnasso, Agostino | Spadea, Maria Francesca

Article Type: Research Article

Abstract: BACKGROUND: Longitudinal Displacement (LD) is the relative motion of the intima-media upon adventitia of the arterial wall during the cardiac cycle, probably linked to atherosclerosis. It has a direction, physiologically first backward in its main components with respect to the arterial flow. Here, LD was investigated in various disease and in presence of a unilateral carotid stent. METHODS: Carotid acquisitions were performed by ultrasound imaging on both body sides of 75 participants (150 Arteries). LD was measured in its percent quantity and direction. RESULTS: Obesity (p  = 0.001) and carotid plaques (p  = 0.01) were independently associated to …quantity decrease of LD in the whole population. In a subgroup analysis, it was respectively 143% in healthy (n  = 48 carotids), 129% (n  = 34) in presence of cardiovascular risk factors, 121% (n  = 20) in MACE patients, 119% (n  = 24) in the carotid contralateral to a stent, 110% (n  = 24) in carotids with stents. Regarding the direction of LD, in a subgroup analysis an inverted movement was identified in aged (p  = 0.001) and diseased (p  = 0.001) participants who also showed less quantity of LD (p  = 0.001), but independently with age only (p  = 0.002) in the whole population. CONCLUSIONS: This observational study suggests that LD within carotid wall layers is lower additively with ageing, cardiovascular risk factors, cardiovascular diseases, and stent. Even if stent is surely beneficial, these data might shed some light on stent restenosis, emphasising the need for interventional studies. Show more

Keywords: Arterial displacement, longitudinal sliding, atherosclerosis, stent

DOI: 10.3233/CH-242357

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 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: Lusha, E. | Zhao, Ping

Article Type: Research Article

Abstract: Myocardial ischemia-reperfusion injury is accompanied by ferroptosis mediated by reactive oxygen species and iron ions, which aggravates myocardial tissue damage. The present study aims to explore the molecular mechanism underlying the mitigating effects f PCSK9 on myocardial ischemia-reperfusion injury. MI/R rat model and OGD/R induced H9c2 model were established. The interaction between PCSK9 inhibitor and LRP8 was predicted by STRING database and verified by Immunoprecipitation assay experiment. CCK-8 kit results confirmed that PCSK9 inhibitor effectively protected against cardiomyocyte damage induced by OGD/R. TTC and histological examination via H&E staining revealed a significant alleviation of myocardial infarction and pathological alterations upon …treatment with the PCSK9 inhibitor. Besides, DCFH-DA staining and biochemical kit results showed that PCSK9 inhibitor could regulate the changes of ferroptosis related indicators [ROS, iron level, MDA, SOD] and inhibit ferroptosis. Rescue experiments showed that PCSK9 inhibitors targeted LRP8 expression and inhibited GPX4/ROS-mediated ferroptosis in I/R-induced rats. Our study suggested that PCSK9 inhibitors could attenuate myocardial I/R injury, with the underlying mechanism intimately tied to the targeted modulation of LRP8/GPX4-mediated ferroptosis. Show more

Keywords: PCSK9 inhibitor, myocardial ischemia-reperfusion, LRP8, ferroptosis

DOI: 10.3233/CH-242444

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

Authors: Li, Wenying | Jiang, Jun | Cao, Jiaying | Wei, Li | Cheng, Rui | Lu, Xiuyun | Dong, Yi

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the value of ultrasound viscosity imaging in preoperative differential diagnosis between malignant and benign breast lesions. METHODS: This prospective study was approved by our institutional review board and informed consents were signed by all patients. Patients diagnosed with focal solid breast lesions who plan to undergo surgical or ultrasound guided core needle biopsy were included. A Mindray Resona R9 Elite diagnostic ultrasound system equipped with a linear array transducer (L15-3 MHz) was used. First BMUS was used to identify the lesions, afterwards, ultrasound viscosity imaging and shear wave elastography measurements were performed for each lesion. Viscosity …(Pa*s) coefficient and shear-wave speed (m/s) of each breast lesion were measured. Taking the final histopathological results as the gold standard, the optimal cut-off value of viscosity and elastography values in differential diagnosis between malignant and benign breast lesions were evaluated. Diagnostic performance was assessed by using the area under the receiver operating characteristic curve (ROC). RESULTS: From July 2023 to March 2024, 159 consecutive patients with a total of 184 solid breast lesions were included. Among which 74 (40.2%) malignant lesions and 110 (59.8%) benign ones were diagnosed according to the final histopathological results. The mean maximal viscosity coefficient (7.56±3.63 Pa*s) of malignant lesions was significantly higher than that of benign ones (4.52±2.33 Pa*s), whereas the mean maximal SWE value (6.53±1.87 m/s) of malignant lesions was also obviously higher than that of benign ones (4.80±1.62 m/s) (P  < 0.05). The cut-off value for diagnosis of malignant breast tumors was 5.39 Pa*s for viscosity, with 75.68% sensitivity, 68.18% specificity and 0.763 AUROC (P  < 0.05). When combined viscosity with SWE values, the sensitivity and specificity was 75.68% and 75.45%, with an-area under the receiver operating characteristic curve (AUC) 0.787. CONCLUSIONS: The value of viscosity measurement may provide additional value for preoperative non-invasive differential diagnosis between malignant and benign breast lesions. Show more

Keywords: Ultrasound imaging, viscosity, shear wave elastography, breast tumors, differential diagnosis

DOI: 10.3233/CH-242405

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

Authors: Sangtarash, F. | Shadmehr, A. | Choobsaz, H. | Fereydounnia, S. | Sadeghi, A. | Jung, F. | Sarfraz, M.

Article Type: Research Article

Abstract: After menopause, there is an imbalance between bone formation and resorption activity, which could lead to postmenopausal osteopenia or osteoporosis. Resistance training (RT) can induce mechanical stress on bone which is necessary for bone remodeling and angiogenic-osteogenic response. This systematic review aims to assess the effects of RT on bone microcirculation and bone turnover markers (BTMs) in postmenopausal women with osteopenia or osteoporosis. We conducted a comprehensive search for related studies published up to April 2023 to identify eligible articles. Out of 316 articles identified, the full texts of 69 articles were screened. There is not any study which …consider the effect of resistance exercises on bone microcirculation in PMOP women, but four articles aseess the effect of RT on BTMs and were reviewed. The quality of the articles was assessed by using the Physiotherapy Evidence Database (PEDro) scale. In one study, after 6 and 12 months of RT, bone formation and bone resorption biomarkers decreased not significantly. According to another study, bone formation and resorption biomarkers increased significantly after 3-months RT. Two other studies reported increases in biomarkers of bone formation along with decreases of biomarkers in bone resorption after 6-months of RT, but these were not significant. However, these results suggest that RT had some beneficial effects on BTMs but it is not an effective tool for modifying BTMs in women with osteoporosis or osteopenia. This may be due to the site-specific skeletal stimulation that RT provides. In addition considering the effect of RT on microcirculation of bone are important. So, there is a need for further, high-quality studies in this field. Show more

Keywords: Resistance training, microcirculation of bone tissue, bone turnover markers, osteopenia, osteoporosis, postmenopausal women

DOI: 10.3233/CH-249105

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