|Cancer||Cell death||Cell cycle||Cytoskeleton||Exo/endocytosis||Differentiation||Division||Organelles||Signalling||Stem cells||Trafficking|
Effects of ghrelin on homocysteine-induced dysfunction and inflammatory response in rat cardiac microvascular endothelial cells
Dongjuan Wang*1, Haichang Wang*1, Peng Luo†1, Andrew Hwang‡, Dongdong Sun*, Yabin Wang*, Zheng Zhang*, Nan Liu*, Shenxu Wang*, Chengxiang Li* and Feng Cao*2
*Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xian, Shaanxi, 710032, †Department of Cardiovascular surgery, Xijing Hospital, Fourth Military Medical University, Xian, Shaanxi, 710032, China, and ‡Department of Radiology, Molecular Imaging Program of Stanford, Stanford University, Stanford, CA, USA
Ghrelin is a well-characterized hormone that has protective effects on endothelial cells. Elevated HCY (homocysteine) can be a cardiovascular risk factor, but it is not known whether ghrelin can inhibit HCY-induced dysfunction and inflammatory response in rat CMECs (cardiac microvascular endothelial cells). We found that HCY treatment for 24 h inhibited proliferation and NO (nitric oxide) secretion, but with increased cell apoptosis and secretion of cytokines in CMECs. In contrast, ghrelin pretreatment significantly improved proliferation and NO secretion, and inhibited cell apoptosis and secretion of cytokines in HCY-induced CMECs. In addition, Western blot assay showed that NF-κB (nuclear factor κB) and cleaved-caspase 3 expression were elevated, and PCNA (proliferating cell nuclear antigen) and eNOS (endothelial nitric oxide synthase) expression were decreased after treatment with HCY, which was significantly reversed by pretreatment with ghrelin. The data suggest that ghrelin inhibits HCY-induced CMEC dysfunction and inflammatory response, probably mediated by inhibition of NF-κB activation.
Key words: cardiac microvascular endothelial cell (CMEC), ghrelin, homocysteine (HCY), inflammatory response, NF-κB
Abbreviations: AG, acylated ghrelin, BrdU, bromodeoxyuridine, CMEC, cardiac microvascular endothelial cell, CVD, cardiovascular disease, DAPI, 4′,6-diamidino-2-phenylindole, eNOS, endothelial nitric oxide synthase, GH, growth hormone, HCY, homocysteine, ICAM-1, intercellular adhesion molecule 1, IκB, inhibitory κB, IL, interleukin, MCP-1, monocyte chemoattractant protein 1, MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, NAC, N-acetyl-K-cysteine, NF-κB, nuclear factor κB, NO, nitric oxide, PCNA, proliferating cell nuclear antigen, PI3K, phosphoinositide 3-kinase, SD, Sprague–Dawley, TUNEL, terminal deoxy-nucleotidyl transferase-mediated dUTP nick end-labelling, UAG, unacylated ghrelin
1These authors have contributed equally to this work.
2To whom correspondence should be addressed (email firstname.lastname@example.org).
Received 14 April 2011/18 January 2012; accepted 17 February 2012
Published as Cell Biology International Immediate Publication 17 February 2012, doi:10.1042/CBI20110235
© The Author(s) Journal compilation © 2012 International Federation for Cell Biology