Cardioprotection by the transfer of coronary effluent from ischaemic preconditioned rat hearts: identification of cardioprotective humoral factors

• Published in: Basic research in cardiology Vol. 112; no. 5; p. 52
• Main Authors: Maciel, Leonardo, de Oliveira, Dahienne F., Verissimo da Costa, Giovani C., Bisch, Paulo M., Nascimento, Jose Hamilton Matheus
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2017; Springer Nature B.V
• Subjects: Animals; Cardiology; Chaperonin 10 - metabolism; Chromatography, Liquid; Disease Models, Animal; Effluents; Heart; Hydrophobicity; Inhibitors; Injuries; Injury prevention; Ischemia; Ischemic Preconditioning, Myocardial; Isolated Heart Preparation; KATP Channels - metabolism; Male; Mass spectrometry; Mass spectroscopy; Medicine; Medicine & Public Health; Molecular weight; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial Infarction - prevention & control; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - prevention & control; Myocardium - metabolism; Myocardium - pathology; Original Contribution; Peptides; Perfusion; Preconditioning; Protein kinase C; Protein Kinase C - metabolism; Proteins; Proteomics - methods; Rats, Wistar; Reperfusion; Rodents; Signal Transduction; Spectrometry, Mass, Electrospray Ionization; Stroke Volume; Tandem Mass Spectrometry; Time Factors; Tissues; Ultrafiltration; Ventricular Function, Left; Ventricular Pressure; Ischaemic preconditioning; Cardioprotection; Ischaemia/reperfusion; Proteomic
• ISSN: 0300-8428; 1435-1803
• DOI: 10.1007/s00395-017-0641-2

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 naïve 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 >50 kDa) and evaluated for cardioprotective effects by perfusion before I/R in naïve 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 K ATP . 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.