期刊
BASIC RESEARCH IN CARDIOLOGY
卷 112, 期 5, 页码 -出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00395-017-0641-2
关键词
Ischaemic preconditioning; Cardioprotection; Ischaemia/reperfusion; Proteomic
资金
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [483639/2013-3]
- Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ) [E-26/112.085/2012]
- CNPq
- FAPERJ
Ischaemic preconditioning (IPC) provides myocardial resistance to ischaemia/reperfusion (I/R) injuries. The protection afforded by IPC is not limited to the target tissue but extends to remote tissues, suggesting a mechanism mediated by humoral factors. The aim of the present study was to identify the humoral factors that are responsible for the cardioprotection induced by the coronary effluent transferred from IPC to naive hearts. Isolated rat hearts were submitted to IPC (three cycles of 5 min I/R) before 30-min global ischaemia and 60-min reperfusion. The coronary effluent (Efl_IPC) collected during IPC was fractionated by ultrafiltration in different molecular weight ranges (<3, 3-5, 5-10, 10-30, 30-50, and >50kDa) and evaluated for cardioprotective effects by perfusion before I/R in naive hearts. Only the <3, 5-10 and <10 kDa fractions of hydrophobic eluate reduced I/R injuries. The cardioprotective effect of the 5-10 fraction was blocked by K-ATP channel blockers and a PKC inhibitor. An Efl_ IPC proteomic analysis revealed 14 cytoprotection-related proteins in 4-12 kDa peptides. HSP10 perfusion protected the heart against I/R injuries. These data provide insights into the mechanisms of cardioprotection in humoral factors released by IPC. Cardioprotection is afforded by hydrophobic peptides in the 4-12 kDa size range, which activate pathways that are dependent on PKC and KATP. Fourteen 4-12 kDa peptides were identified, suggesting a potential therapeutic role for these molecules in ischaemic diseases. One of these, HSP10, identified by mass spectrometry, reduced I/R injuries and may be a potential candidate as a therapeutic target.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据