Plasma Levels of Liver-Specific miR-122 is Massively Increased in a Porcine Cardiogenic Shock Model and Attenuated by Hypothermia.

AIMS:: Tissue-specific circulating microRNAs are released into the blood after organ injury. In an ischemic porcine cardiogenic shock model we investigated the release pattern of cardiacspecific miR-208b and liver-specific miR-122 and assessed the effect of therapeutic hypothermia on their respective plasma levels. METHODS AND RESULTS:: Pigs were anesthetized and cardiogenic shock was induced by inflation of a PCI-balloon in the proximal LAD for 40 minutes followed by reperfusion. After fulfillment of the predefined shock criteria, the pigs were randomized to hypothermia (33°C, n=6) or normothermia (38°C, n=6). Circulating microRNAs were extracted from plasma and measured with quantitative real-time PCR. Tissue specificity was assessed by microRNA extraction from porcine tissues followed by quantitative real-time PCR. In vitro, the release of miR-122 from a cultured hepatocyte cell line exposed to either hypoxia or acidosis was assessed by real-time PCR. miR-122 was found to be highly liver specific whereas miR-208b was expressed exclusively in the heart. In the control group ischemic cardiogenic shock induced a 460.000-fold and a 63.000-fold increase in plasma levels of miR-122 (p<0.05) and miR-208b (p<0.05), respectively. Therapeutic hypothermia significantly diminished the increase of miR-122 compared to the normothermic group (p<0.005). In our model, hypothermia was initiated after coronary reperfusion and did neither affect myocardial damage as previously assessed by magnetic resonance imaging nor the plasma level of miR-208b. CONCLUSIONS:: Our results indicate that liver-specific miR-122 is released into the circulation in the setting of cardiogenic shock and that therapeutic hypothermia significantly reduces the levels of miR-122.