Clinical Hemorheology and Microcirculation - Volume 88, issue 2

Authors: Wang, Yali | Ye, Qing | Cui, Yongqi | Wu, Yunjiang | Cao, Sipei | Hu, Feng

Article Type: Research Article

Abstract: BACKGROUND: Pulmonary hypertension (PH) is a refractory disease characterized by elevated pulmonary artery pressure and resistance. Drag-reducing polymers (DRPs) are blood-soluble macromolecules that reduce vascular resistance by altering the blood dynamics and rheology. Our previous work indicated that polyethylene oxide (PEO) can significantly reduce the medial wall thickness and vascular resistance of the pulmonary arteries, but the specific mechanism is still unclear. METHODS: This study was designed to investigate the role and mechanism of PEO on intracellular calcium [Ca2 + ] i and cytoskeletal proteins of endothelial cells (ECs) induced by low shear stress (LSS) in PH. Primary …Pulmonary Artery Endothelial Cells (PAECs) were subjected to steady LSS (1 dyn/cm2 ) or physiological shear stress (SS) (10 dyn/cm2 ) for 20 h in a BioFlux 200 flow system. Calcium influx assays were conducted to evaluate the mechanisms of PEO on [Ca2 + ] i . Subsequently, taking the key protein that induces cytoskeletal remodeling, the regulatory light chain (RLC) phosphorylation, as the breakthrough point, this study focused on the two key pathways of PEO that regulate phosphorylation of RLC: Myosin light chain kinase (MLCK) and Rho-associated kinase (ROCK) pathways. RESULTS: Our current research revealed that PEO at LSS (1 dyn/cm2 ) significantly suppressed LSS-induced [Ca2 + ] i and the expression level of transient receptor potential channel 1(TRPC1). In addition, ECs convert LSS stimuli into the upregulation of cytoskeletal proteins, including filamentous actin (F-actin), MLCK, ROCK, p-RLC, and pp-RLC. Further experiments using pharmacological inhibitors demonstrated that PEO at the LSS downregulated cytoskeleton-related proteins mainly through the ROCK and MLCK pathways. CONCLUSIONS: This study considered intracellular calcium and cytoskeleton rearrangement as entry points to study the application of PEO in the biomedical field, which has important theoretical significance and practical application value for the treatment of PH. Show more

Keywords: Pulmonary hypertension, drag-reducing polymers, shear stress, myosin light chain kinase, Rho-associated kinase

DOI: 10.3233/CH-242281

Citation: Clinical Hemorheology and Microcirculation, vol. 88, no. 2, pp. 247-261, 2024

Authors: Tang, Feng | Tian, Long-hai | Zhu, Xiao-han | Yang, Sen | Zeng, Huan | Yang, Yong-yao

Article Type: Research Article

Abstract: BACKGROUND: The precise association between lncRNA H19 and ferroptosis in the context of atherosclerosis remains uncertain. OBJECTIVE: This study is to clarify the underlying process and propose novel approaches for the advancement of therapeutic interventions targeting atherosclerosis. METHODS: Assessment of ferroptosis, which entails the evaluation of cell viability using CCK-8 and the quantification of intracellular MDA, GSH, and ferrous ions. Simultaneously, the protein expression levels of assessed by western blot analysis, while the expression level of lncRNA H19 was also determined. Furthermore, HAECs that were cultured with ox-LDL were subjected to Fer-1 interference. HAECs were exposed …to ox-LDL and then transfected with H19 shRNA and H19 overexpression vector pcDNA3.1. The level of ferroptosis in the cells was then measured. Then, HAECs were subjected to incubation with ox-LDL, followed by transfection with H19 shRNA and treated with Erastin to assess the levels of ferroptosis, cell viability, and inflammatory factor production. and the ability for blood vessel development. RESULTS: The survival rate of HAECs in the ox-LDL group was much lower. Ox-LDL resulted in an upregulation of ACSL4 expression in HAECs, while the expression of SLC7A11 and GPX4 decreased. CONCLUSIONS: lncRNA H19 enhances ferroptosis and exacerbates arterial endothelial cell damage induced by LDL. Show more

Keywords: lncRNA H19, ferroptosis, arterial endothelial cell damage

DOI: 10.3233/CH-242261

Citation: Clinical Hemorheology and Microcirculation, vol. 88, no. 2, pp. 263-275, 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. 88, no. 2, pp. 277-288, 2024

Authors: Tastekin, Fatih | Akay, Olga Meltem | Colak, Ertugrul | Gunduz, Eren

Article Type: Research Article

Abstract: BACKGROUND: Although plateletpheresis donation is commonly accepted as a safe procedure, its influence on platelet function, coagulation system and fibrinolysis is not completely elucidated. OBJECTIVES: In this study, we tried to assess the effects of plateletpheresis on donor’s hemostasis system by measuring platelet activation, development of platelet-leukocyte aggregates, and coagulation activation. STUDY DESIGN: Prospective observational study. METHODS: We used flow cytometry to determine the levels of platelet-monocyte complexes (PMC) and platelet-neutrophil complexes (PNC). sP-selectin and prothrombin fragment (PF) 1 + 2 values were determined by ELISA. RESULTS: The PMC levels increased significantly seven days …after apheresis in comparison with just after apheresis and 24 h after apheresis (p  < 0.05). The PNC levels increased significantly seven days after apheresis compared to immediately after apheresis (p  < 0.05). sP-selectin values decreased significantly immediately after apheresis (p  < 0.05). While sP-selectin values increased seven days after apheresis in comparison with immediately after apheresis and 24 h after apheresis, but there were not statistically significant differences for sP-selectin levels (p  > 0.05). PF1 + 2 levels decreased significantly immediately after apheresis compared to pre-apheresis (p  < 0.05) and increased 24 h after apheresis and seven days after apheresis, but these differences were not statistically significant. CONCLUSION: We concluded that plateletpheresis affects platelet activation but does not cause any change in coagulation activation. Show more

Keywords: Plateletpheresis, platelet-leucocyte aggregate, P-selectin, prothrombin fragment

DOI: 10.3233/CH-242325

Citation: Clinical Hemorheology and Microcirculation, vol. 88, no. 2, pp. 289-296, 2024

Authors: Velcheva, Irena | Antonova, Nadia | Kmetski, Tsocho | Tsonevska, Galina | Stambolieva, Katerina | Alexandrova, Anika | Bechev, Blagovest

Article Type: Research Article

Abstract: OBJECTIVE: The carotid stiffness is an important factor in the pathogenesis of cerebrovascular small vessel disease. Our study aimed to evaluate the relation of the local arterial stiffness of the common carotid artery (CCA) to the hemodynamic forces and blood viscosity in patients with cerebral lacunar infarctions (LI). METHODS: Twenty-two patients with chronic LI and 15 age-matched controls were examined. An ultrasound examination of the CCA intima-media thickness (IMT), the parameters of local CCA stiffness: distensibility (DC) and compliance coefficients (CC), α and β stiffness indices and pulse wave velocity (PWV) was performed. The local hemodynamic forces …were calculated: circumferential wall tension (CWT) and wall shear stress (WSS). Whole blood viscosity (WBV) and shear stresses at shear rates of 0.277 s- 1 to 94.5 s- 1 were measured in patients and controls. RESULTS: Higher values of IMT, a significant decrease of DC and CC and an increase of α and β stiffness indices and PWV in the LI patients compared to the controls were obtained. A parallel significant increase in CWT and a decrease in WSS was found. An increase in WBV and a significant increase in shear stresses were detected. In the LI patients, the increased stiffness indices were associated with an increase in age, cholesterol and WBV at higher shear rates in the left CCA. In the controls, the IMT and stiffness indices correlated significantly with the hemodynamic factors and WBV in both CCAs, while the stiffness indices correlated with the hemodynamic forces in the left CCA. CONCLUSION: The results of the present study demonstrate different associations of the local carotid stiffness indices with the hemodynamic forces and WBV in patients with LI and controls. Show more

Keywords: Lacunar infarctions, common carotid artery, intima-media thickness, local carotid stiffness, hemodynamic forces, whole blood viscosity

DOI: 10.3233/CH-242333

Citation: Clinical Hemorheology and Microcirculation, vol. 88, no. 2, pp. 297-308, 2024