Suppression of proatherogenic leukocyte interactions by MCS-18 - Impact on advanced atherosclerosis in ApoE-deficient mice

Kühn C, Tauchi M, Stumpf C, Daniel C, Bäuerle T, Schwarz M, Kerek F, Steinkasserer A, Zinser E, Achenbach S, Dietel B (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Atherosclerosis Elsevier

Book Volume: 245

Pages Range: 101-10

DOI: 10.1016/j.atherosclerosis.2015.12.001

Abstract

Atherosclerosis is associated with chronic inflammatory responses of the arterial blood vessels. The previously observed protective effect of the MCS-18 substance against the initiation of atherosclerosis in a murine model was explained by its pronounced anti-inflammatory activity. Here, we investigated its impact on murine plaque progression in advanced atherosclerosis and on proatherogenic processes.ApoE-deficient mice were fed a high-fat diet for 12 weeks to induce atherosclerosis, followed by normal chow and intraperitoneal injections of either MCS-18 (500 ?g, n = 10) or saline (n = 10) twice a week for another 12 weeks. Plaque size was reduced in MCS-18 treated mice compared to controls (p = 0.001), which was associated with a reduced size of the lipid core (p = 0.01). There was a decrease in apoptotic cells (p = 0.02), endothelial ICAM-1 expression (p < 0.001), and macrophage density (p = 0.01) in the MCS-18 group. In addition, human and murine dendritic cells (DCs) and human umbilical vein endothelial cells (HUVECs) were treated with MCS-18 (50-200 ?g/ml) to analyze cell migration and adhesion under flow conditions. MCS-18 reduced human (p = 0.01) and murine (p = 0.006) DC migration. Furthermore, adhesion of MCS-18-treated DCs to a HUVEC monolayer was decreased (p < 0.001). Compared to controls, CD209 (p < 0.001) and CCR7 (p = 0.003) expression was decreased in MCS-18-treated DCs, while in HUVECs lower levels of ICAM-1 (p < 0.001) and of phosphorylated NF-?B-p65 (p = 0.002) were observed. Blocking of ICAM-1 reduced DC adhesion (p < 0.001).MCS-18 exhibits interesting therapeutic effects when applied in advanced murine atherosclerosis. Its antiatherogenic impact might be associated with a suppressed adhesion to the endothelium due to down-regulation of endothelial ICAM-1 expression.

Authors with CRIS profile

Constanze Kühn Department of Medicine 2 – Cardiology and Angiology Christian Stumpf Department of Medicine 2 – Cardiology and Angiology Tobias Bäuerle Professur für Multimodale Bildgebung in der präklinischen Forschung Alexander Steinkasserer Professur für Experimentelle Dermatologie Stephan Achenbach Department of Medicine 2 – Cardiology and Angiology Barbara Dietel Graduiertenzentrum der FAU

Involved external institutions

DoNatur GmbH DE Germany (DE)

How to cite

APA:

Kühn, C., Tauchi, M., Stumpf, C., Daniel, C., Bäuerle, T., Schwarz, M.,... Dietel, B. (2016). Suppression of proatherogenic leukocyte interactions by MCS-18 - Impact on advanced atherosclerosis in ApoE-deficient mice. Atherosclerosis, 245, 101-10. https://doi.org/10.1016/j.atherosclerosis.2015.12.001

MLA:

Kühn, Constanze, et al. "Suppression of proatherogenic leukocyte interactions by MCS-18 - Impact on advanced atherosclerosis in ApoE-deficient mice." Atherosclerosis 245 (2016): 101-10.

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