Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Cell Biol Int. 2012 Jun 1;36(6):511-7. doi: 10.1042/CBI20110235.
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.
生长激素释放肽是一种特征明确的激素，对血管内皮细胞具有保护作用。高同型半胱氨酸（HCY）可作为心血管风险因素，但尚不清楚生长激素释放肽是否能抑制 HCY 诱导的大鼠 CMECs（心脏微血管内皮细胞）功能障碍和炎症反应。我们发现，HCY 处理 24 小时可抑制细胞增殖和一氧化氮（NO）分泌，但增加细胞凋亡和细胞因子分泌。相比之下，生长激素释放肽预处理可显著改善 HCY 诱导的 CMECs 增殖和 NO 分泌，并抑制细胞凋亡和细胞因子分泌。此外，Western blot 检测显示，HCY 处理后核因子 κB（NF-κB）和裂解型半胱天冬酶 3 表达升高，增殖细胞核抗原（PCNA）和内皮型一氧化氮合酶（eNOS）表达降低，而生长激素释放肽预处理可显著逆转这种情况。数据表明，生长激素释放肽抑制 HCY 诱导的 CMEC 功能障碍和炎症反应，可能是通过抑制 NF-κB 激活介导的。
