Role of growth hormone signaling pathways in the development of atherosclerosis

• Published in: Growth hormone & IGF research Vol. 53-54; p. 101334
• Main Authors: Ishikawa, Mayumi, Toyomura, Junko, Yagi, Takashi, Kuboki, Koji, Morita, Toshisuke, Sugihara, Hitoshi, Hirose, Takahisa, Minami, Shiro, Yoshino, Gen
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.08.2020
• Subjects: Atherosclerosis; Cell signaling; Growth hormone; Growth hormone; Cell signaling; Atherosclerosis
• ISSN: 1096-6374; 1532-2238
• DOI: 10.1016/j.ghir.2020.101334

The direct actions of growth hormone (GH) in the development of atherosclerosis are unclear. The goal of this study was to characterize GH-induced changes in expression of signaling pathway elements and other proteins that may be related to atherosclerosis. Human umbilical vein endothelial cells (HUVEC) and THP-1, a human acute monocytic leukemia cell line, were stimulated by exposure to 10−9 M or 10−8 M human GH with or without pretreatment with a mitogen-activated protein kinase kinase (MEK) 1 inhibitor. Levels of transcripts encoding vascular cell adhesion molecule (VCAM) -1, E-selectin, monocyte chemotactic protein (MCP-1), interleukin (IL) -6, and IL-8 were investigated by reverse transcription (RT) -PCR. For the quantitative adhesion assay, THP-1 cells or human primary monocytes were fluorescently labeled with 3’-O-acetyl-2′,7′-bis(carboxyethyl) -4 diacetoxymethyl ester (BCECF/AM). HUVEC treated with human GH were co-incubated with BCECF-labeled THP-1 cells. One hour later, the number of BCECF-labeled THP-1 cells was assessed. An equivalent experiment was performed using BCECF-labeled primary monocytes, and the number of monocytes adhering to HUVEC was counted. Treatment with hGH increased the levels of E-selectin- and VCAM-1-encoding mRNAs in HUVEC. This effect was attenuated by pretreatment with a MEK1 inhibitor. Furthermore, hGH treatment increased adhesion of BCECF-labeled THP-1 cells or primary monocytes to HUVEC, and this effect was attenuated by pretreatment with a MEK1 inhibitor. VCAM-1 and E-selectin expression was stimulated by GH via the mitogen-activated protein kinase pathway, resulting in augmented adhesion of THP-1 cells and monocytes to HUVEC. These data suggested that GH directly stimulates the development of atherosclerosis. •GH increased mRNA expressions of VCAM-1 and E-selectin on HUVEC.•The GH effects were suppressed by MEK-1 inhibitor, but not by JAK2 inhibitor.•GH increased THP-1, which is human acute monocytic leukemia cell line, attachment to HUVEC.•The attachment was suppressed by MEK1 inhibitor.•These data suggest that GH stimulates development of atherosclerosis via srk-erk pathway without IGF-I.