Agnieszka M Kolodziejczyk1, Marta Targosz-Korecka2, Marek Szymonski2. 1. Research Centre for Nanometer-Scale Science and Advanced Materials, NANOSAM, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, Kraków, Poland; Bionanopark Ltd., Łódź, Poland. Electronic address: aga.szczygiel@gmail.com. 2. Research Centre for Nanometer-Scale Science and Advanced Materials, NANOSAM, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, Kraków, Poland.
Abstract
BACKGROUND: The pharmacological treatment of cardiovascular diseases that may potentially be attributed to endothelial dysfunction often requires the application of endothelium-targeted drugs. Simvastatin is one of such drugs currently on the market due to its established anti-inflammatory activities. The nanomechanical response to drug treatment at the cellular level is not yet known. However, this response mechanism is promising as a prospective testing method for newly developing drugs. METHODS: Force spectroscopy was used for in vitro characterization of the elastic properties of human microvascular endothelial cells. Cell dysfunction was caused by the application of tumor necrosis factor alpha. The anti-inflammatory action of the compounds was investigated for the cells incubated with each of the following agents: simvastatin, pyridine derivatives (1,4-dimethylpyridine chloride (1,4-DMP), and 1-methylpyridinium chloride (1-MP)). Moreover, in the case of 1,4-DMP and 1-MP, the measurements were supplemented with F-actin labeling data. RESULTS: We measured the simvastatin influence on the elasticity of human microvascular endothelial cells (HMECs) for concentrations: 1, 10 and 100μM. Furthermore, we evaluated the therapeutic and preventive effects of 1μM drug on inflamed cells. Finally, the effect of pyridine derivatives 1,4-dimethylpyridine chloride (1,4-DMP) and 1-methylpyridinium chloride (1-MP) was tested using force spectroscopy. CONCLUSIONS: The anti-inflammatory activity of the simvastatin is well illustrated by the endothelium cell elasticity changes returning from the characteristic inflammation time cycle "soft-stiff-soft" to control values. Furthermore, the elasticity results and F-actin labeling data indicated a preventive effect for 1- MP, whereas 1,4-DMP does not exhibit endothelium activity even at toxic concentrations.
BACKGROUND: The pharmacological treatment of cardiovascular diseases that may potentially be attributed to endothelial dysfunction often requires the application of endothelium-targeted drugs. Simvastatin is one of such drugs currently on the market due to its established anti-inflammatory activities. The nanomechanical response to drug treatment at the cellular level is not yet known. However, this response mechanism is promising as a prospective testing method for newly developing drugs. METHODS: Force spectroscopy was used for in vitro characterization of the elastic properties of human microvascular endothelial cells. Cell dysfunction was caused by the application of tumor necrosis factor alpha. The anti-inflammatory action of the compounds was investigated for the cells incubated with each of the following agents: simvastatin, pyridine derivatives (1,4-dimethylpyridine chloride (1,4-DMP), and 1-methylpyridinium chloride (1-MP)). Moreover, in the case of 1,4-DMP and 1-MP, the measurements were supplemented with F-actin labeling data. RESULTS: We measured the simvastatin influence on the elasticity of human microvascular endothelial cells (HMECs) for concentrations: 1, 10 and 100μM. Furthermore, we evaluated the therapeutic and preventive effects of 1μM drug on inflamed cells. Finally, the effect of pyridine derivatives 1,4-dimethylpyridine chloride (1,4-DMP) and 1-methylpyridinium chloride (1-MP) was tested using force spectroscopy. CONCLUSIONS: The anti-inflammatory activity of the simvastatin is well illustrated by the endothelium cell elasticity changes returning from the characteristic inflammation time cycle "soft-stiff-soft" to control values. Furthermore, the elasticity results and F-actin labeling data indicated a preventive effect for 1- MP, whereas 1,4-DMP does not exhibit endothelium activity even at toxic concentrations.
Authors: Waleed Y Rizg; Khaled M Hosny; Bayan A Eshmawi; Abdulmohsin J Alamoudi; Awaji Y Safhi; Samar S A Murshid; Fahad Y Sabei; Adel Al Fatease Journal: Polymers (Basel) Date: 2022-05-07 Impact factor: 4.967