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

Authors: Hong, Ji-Ge | Zheng, Hui-Lei | Wang, Peng | Huang, Ping | Gong, Dan-Ping | Zeng, Zhi-Yu

Article Type: Research Article

Abstract: Circular RNAs (circRNAs) have been reported to participate in the development of various diseases. In this study, we investigated the potential mechanism underlying the role of circRNAs in atherosclerosis. Human umbilical vein endothelial cells (HUVECs) were treated with 100 μg/mL oxidized low-density lipoprotein (ox-LDL) to simulate atherosclerosis. We observed that hsa_circ_0006867 (circ_0006867), a circRNA markedly increased in ox-LDL-treated endothelial cells, acted as a molecular sponge of miR-499a-3p and regulated its expression. This interaction led to changes in the downstream target gene ADAM10, thus affecting cell apoptosis and migration. Thus, our study suggests that circ_0006867 regulates ox-LDL-induced endothelial injury via the …circ_0006867/miR-499a-3p/ADAM10 axis, indicating its potential as an exploitable therapeutic target for atherosclerosis. Show more

Keywords: Atherosclerosis, ox-LDL, circ_0006867, miR-499a-3p, endothelial cells, ADAM10

DOI: 10.3233/CH-231895

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

Authors: Kordi, Negin | Sanaei, Masoumeh | Akraminia, Peyman | Yavari, Sajad | Saydi, Ali | Abadi, Fatemeh Khamis | Heydari, Naser | Jung, Friedrich | Karami, Sajad

Article Type: Research Article

Abstract: Regulated cell death, including pyroptosis, apoptosis, and necroptosis, is vital for the body’s defense system. Recent research suggests that these three types of cell death are interconnected, giving rise to a new concept called PANoptosis. PANoptosis has been linked to various diseases, making it crucial to comprehend its mechanism for effective treatments. PANoptosis is controlled by upstream receptors and molecular signals, which form polymeric complexes known as PANoptosomes. Cell death combines necroptosis, apoptosis, and pyroptosis and cannot be fully explained by any of these processes alone. Understanding pyroptosis, apoptosis, and necroptosis is essential for understanding PANoptosis. Physical exercise has been …shown to suppress pyroptotic, apoptotic, and necroptotic signaling pathways by reducing inflammatory factors, proapoptotic factors, and necroptotic factors such as caspases and TNF-alpha. This ultimately leads to a decrease in cardiac structural remodeling. The beneficial effects of exercise on cardiovascular health may be attributed to its ability to inhibit these cell death pathways. Show more

Keywords: PANoptosis, pyroptosis, apoptosis, necroptosis, activity, training

DOI: 10.3233/CH-242396

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

Authors: Li, Lisha | Wang, Hongjun | Pan, Yalong | Liu, Kun

Article Type: Research Article

Abstract: BACKGROUND: This article reviews the latest research results of the use of ultrasound technology in the perioperative period of carotid endarterectomy and carotid stenting and discusses the role of ultrasound technology in accurately evaluating carotid stenosis and plaque stability, assisting in selecting the most suitable surgical method, and providing optimal perioperative imaging to guide carotid endarterectomy (CEA) and carotid artery stenting (CAS) to reduce the occurrence and progression of stroke. METHODS: The research published in recent years on the application of ultrasound in the perioperative period of CEA and CAS was reviewed through the databases of CNKI, Pubmed, …and Web of Science. RESULTS: Ultrasound has high clinical value in preoperative screening for indications, assessing the degree of carotid artery stenosis and the nature of plaque; monitoring hemodynamic changes intraoperatively to prevent cerebral ischemia or overperfusion; and evaluating surgical outcomes postoperatively and in late follow-up review. CONCLUSION: Ultrasound is currently widely used perioperatively in CEA and CAS and has even become the preferred choice of clinicians to evaluate the efficacy of surgery and follow-up. The presence of vulnerable plaque is an important risk factor for ischemic stroke. Contrast-enhanced ultrasound is an excellent tool to assess plaque stability. In most studies, ultrasound has been used only in a short follow-up period after CEA and CAS, and data from longer follow-ups are needed to provide more reliable evidence. Show more

Keywords: Carotid artery stent implantation, carotid artery ultrasound, carotid endarterectomy, ischemic stroke, neovascularization

DOI: 10.3233/CH-242412

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

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: Blankfield, Robert P.

Article Type: Research Article

Abstract: Endothelial dysfunction, the earliest manifestation of atherosclerosis, can be initiated by both biochemicals and biomechanical forces. Atherosclerosis occurs predominantly at arterial branch points, arterial bifurcations and the curved segments of great arteries. These are the regions that blood flows turbulently. Turbulence promotes endothelial dysfunction by reducing shear stress upon endothelial cells. The endothelial glycocalyx mediates the effect of shear stress upon the endothelium. A mathematical analysis of cardiovascular hemodynamics demonstrates that fluid retention increases turbulence of blood flow. While there is no empirical data confirming this relationship, fluid retention is associated with adverse cardiovascular events. Every medical condition that …causes fluid retention is associated with increased risk of both atherosclerotic cardiovascular disease and venous thromboembolic disease. In addition, most medications that cause fluid retention are associated with increased adverse cardiovascular effects. Calcium channel blockers (CCBs) and pioglitazone are exceptions to this generalization. Even though data regarding CCBs and pioglitazone contradict the hypothesis that fluid retention is a cardiovascular risk factor, these medications have favorable cardiovascular properties which may outweigh the negative effect of fluid retention. Determining whether or not fluid retention is a cardiovascular risk factor would require empirical data demonstrating a relationship between fluid retention and turbulence of blood flow. While this issue should be relevant to cardiovascular researchers, clinicians and patients, it is especially pertinent to the pharmaceutical industry. Four-dimensional magnetic resonance imaging and vector flow Doppler ultrasound have the capability to quantify turbulence of blood flow. These technologies could be utilized to settle the matter. Show more

Keywords: Fluid retention, cardiovascular risk factor, endothelial dysfunction, turbulence, atherosclerotic cardiovascular disease, venous thromboembolic disease

DOI: 10.3233/CH-242128

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

Authors: Kaiser, Ulrich | Kaltenhauser, Simone | Kaiser, Florian | Vehling-Kaiser, Ursula | Herr, Wolfgang | Stroszczynski, Christian | Becker, Claus | Dropco, Ivor | Jung, Ernst Michael

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: Ultrasound-guided interventions (such as biopsies) of unclear lesions are indicated if microcirculatory changes indicate possible malignant lesions. These place high demands on the ultrasound device used. In order to potentially reduce the often associated high technical effort, the wireless ultrasound device Vscan AirTM was examined as a possible ultrasound device for the intervention biopsy. METHODS: As part of an advanced training course on Computertomographie- and ultrasound-guided biopsy and ablation procedures, participants were asked about the image quality of the handheld device used by means of questionnaires. Various lesions were evaluated at a depth of …1.0 to 5.0 cm in an in vitro liver model. The image quality was evaluated independently before, during and after the intervention. The rating scale contained values from 0 (no assessment possible) to 5 (maximum high image quality). A high-end device was used as a reference. RESULTS: A total of 11 participants took part in the study (n  = 4 male [36.4%], n  = 7 female [63.6%]). A total of five tumor like lesions at different depths (1 cm, 2 cm, 3 cm, 4 cm, >4 cm) were assessed separately. In all cases, an adequate biopsy of the target lesion (1 cm in length, core filling 5 mm) was successful. From a depth of 3 cm, the image quality of the mobile device increasingly decreased, but the image quality of the high-end system was still not impaired. Compared to the high-end device, there was a highly significant difference in image quality from a depth of 3 cm (p  < 0.01). Assessment by inexperienced examiners using a handheld device was adequately possible. CONCLUSIONS: Mobile interventional ultrasound represents a potential alternative for the biopsy of unclear tumorous lesions with microcirculatory disorders with limited depth localization. Show more

Keywords: Ultrasound, mobile ultrasound, high end ultrasound, in vitro model, tumor diagnostics, ultrasound interventions

DOI: 10.3233/CH-248104

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

Authors: Martin, Frank | Neubert, Annemarie | Lutter, Anne-Helen | Scholka, Jenny | Hentschel, Erik | Richter, Heiko | Anderer, Ursula

Article Type: Research Article

Abstract: BACKGROUND: Tissue engineering enables the production of three-dimensional microtissues which mimic naturally occurring conditions in special tissues. These 3D culture systems are particularly suitable for application in regenerative medicine or experimental pharmacology and toxicology. Therefore, it is important to analyse the cells in their 3D microenvironment with regard to viability and differentiation. Tetrazolium assays (WST-8 and MTS) are still the methods of choice for estimating the number of living, metabolically active cells, with WST-8 being cell-impermeable compared to MTS. In contrast to these methods, the ATP assay is an endpoint method based on the luciferase-induced reaction of ATP with luciferin …after cell lysis. OBJECTIVE: We compared three methodologically different proliferation/toxicity assays (MTS, WST-8, ATP) in monolayer (2D) and 3D culture systems to improve the technically challenging determination of the number of viable cells. METHODS: Chondrocytes were isolated from human articular cartilage. Three different test systems (MTS, WST-8, ATP) were applied to monolayer cells (2D, varying cell numbers) and spheroids (3D, different sizes) in 96-well plates. The intracellular ATP concentration was determined by luciferase-induced reaction of ATP with luciferin using a luminometer. Formazan formation was measured spectrophotometrically after different incubation periods. Evaluation was performed by phase contrast microscopy (toxicity), correlation of cell count and ATP concentration or absorption signal (Gompertz function) and propidium iodide (PI) staining to proof the cell lysis of all cells in spheroids. RESULTS: In 2D culture, all three assays showed a good correlation between the number of seeded cells and the ATP concentration or absorption data, whereas the MTS-assay showed the lowest specificity. In 3D culture, the spheroid sizes were directly related to the number of cells seeded. The absorption data of the WST-8 and MTS assay correlated only for certain spheroid size ranges, whereas the MTS-assay showed again the lowest specificity. Only the measured intracellular ATP content showed a linear correlation with all spheroid sizes ranging from 100–1000 μm. The WST-8 assay revealed the second-best sensitivity which allows the measurement of spheroids larger than 240 μm. Phase contrast observation of monolayer cells showed toxic effects of MTS after 6 h incubation and no signs of toxicity of WST-8. Staining with propidium iodide showed complete lysis of all cells in a spheroid in the ATP assay. CONCLUSION: Among tetrazolium-based assays, WST-8 is preferable to MTS because of its non-toxicity and better sensitivity. When determining the number of viable cells in the 2D system, caution is advised when using the ATP assay because of its two-phase slope of the correlation graph concerning cell number and intracellular ATP. In 3D systems of human chondrocytes, the ATP-assay is superior to the other two test systems, as the correlation graph between cell number and intracellular ATP is biphasic. Since differentiation processes or other metabolic events can influence the results of proliferation and toxicity assays (determination of viable cells), this should be taken into account when using these test systems. Show more

Keywords: ATP assay, MTS, WST-8, human chondrocytes, spheroid, 3D culture, 2D culture

DOI: 10.3233/CH-248101

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-17, 2024

Authors: Christer, T. | Hüner, A. | Robering, J.W. | Mrowietz, C. | Hiebl, B.

Article Type: Research Article

Abstract:  The pig (Sus scrofa ) is the most widely used large animal model in Europe, with cardiovascular research being one of the main areas of application. Adequate refinement of interventional studies in this field, meeting the requirements of Russell and Burch’s 3 R concept, can only be performed if blood-contacting medical devices are hemocompatible. Because most medical devices for cardiovascular interventional procedures are developed for humans, they are tested only for compatibility with human blood. The aim of this study was therefore to determine whether there are differences in behavior of human and porcine platelets from commercial hybrid …pigs when they come into contact with borosilicate glass, which was used as an exemplary thrombogenic material. For this purpose, changes in platelet count, platelet volume and platelet expression of the activation markers CD61, CD62P and CD63 were measured using a modified chandler loop-system simulating the fluidic effects of the bloodflow. Commercial hybrid pig and human platelets showed significant adhesions to borosilicate glass but the commercial hybrid pigs platelets showed a significantly higher tendency to adhere to borosilicate glass. In contrast to human platelets the platelets of commercial hybrid pigs showed significant activation after 4 to 8 minutes exposure to borosilicate glass and there were differences among the ratios of surface and activation markers in between the platelets of both species. Show more

Keywords: Pig, commercial hybrid pig, platelet activation, platelet count, platelet volume, FACS, CD42a, CD61, CD62P, CD63

DOI: 10.3233/CH-248103

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

Authors: Kaiser, Ulrich | Kück, Fabian | Stroszczynski, Christian | Jung, Ernst Michael | Greiner, Barbara

Article Type: Research Article

Abstract: OBJECTIVE: To assess diagnostic capabilities of a modern handheld ultrasound device (HUD) for portal vein (PV) evaluation in pediatric patients and to verify if age, body mass index (BMI) and object depth correlate to imagequality. METHODS: 45 patients (3.9 months– 17.9 years; 10.3 years±5.4) were examined using a HUD and cart-based high-end ultrasound system (HEUS). The intra-and extrahepatic PV was scanned using B-Mode and Color-coded Doppler sonography (CCDS). A five-point Likert scale was applied to evaluate image quality. Results were interpreted by two readers in consensus. Scores were compared between the scanners and correlated to age, BMI and …skin-to-portal-vein-distance (SPVD). The influence on image quality and the difference between the two devices were analyzed using ordinal and Bayesian logistic regression models. RESULTS: ≥4 points (mild or no limitations) were achieved by the HUD in 60% for B-Mode and 56% for CCDS. There was a statistically significant negative correlation between the image quality achieved by the HUD and the SPVD for B-Mode and CCDS. The effect of BMI and SPVD on having≥4 points differed significantly between the HUD and HEUS for B-Mode (OR = 0.191, p  = 0.005, and OR = 0.040, p  = 0.008) and for CCDS (OR = 0.209, p  = 0.009, and OR = 0.084,p  = 0.011). CONCLUSIONS: Sufficient to excellent image quality for portal vein assessment in pediatric patients was achieved by the HUD except for the most deep-lying structures. Compared to HEUS, diagnostic performance of the HUD is lower, based on a negative correlation with object depth. Show more

Keywords: Handheld ultrasound, Vscan Air, vascular, portal vein, pediatric

DOI: 10.3233/CH-248105

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