The long non-coding RNA Heat4 is dynamically regulated during cardiogenic shock

Abstract

Abstract Background and purpose Cardiogenic shock (CS) remains the leading cause of death in acute myocardial infarction (AMI), with high mortality rates of 40–50%. The long non-coding RNA (lncRNA) Heat4 is associated with the inflammatory response of non-classical monocytes. Previous experimental work shows that this mechanism may be important in heart failure (HF) and during regeneration after vascular injury. Here, we investigate the association of Heat4 with survival in patients with chronic HF and assessed its regulation in AMI and CS. Methods and results Heat4 was elevated in the blood of HF patients compared to age-matched non-failing controls (+5.2-fold; HF: N=63; Controls: N=38; p<0.05). Heat4 showed a positive correlation with systemic inflammation (hsCRP; r=0.41; p<0.05) and was negatively associated with LVEF (r=−0.45; p<0.001). Heat4 blood levels showed good discriminatory power for prevalence of HF (AUC = 0.734; p<0.05) and mortality prediction after 4-year follow-up (AUC = 0.789; HF: Death N=32; Controls: Death N=0; p<0.05). Furthermore, Heat4 was elevated in the blood of patients with AMI compared to controls (+1.85-fold; AMI: N=42; Controls: N=23; p<0.05). Heat4 showed a very strong induction in patients suffering from CS (+284.5-fold; CS: N=4; Controls: N=5; p<0.05). In agreement with an anti-inflammatory signaling, Heat4 showed a dynamic regulation in patients with CS with a 284.5-fold increase during acute shock and a decrease 24 hours after revascularization (−82.3% compared to day of revascularization). This regulation was validated in an independent second cohort. Conclusion The lncRNA Heat4 is upregulated in the blood of patients with chronic heart failure, acute myocardial infarction and cardiogenic shock. In CS, Heat4 is dynamically regulated. These data set the stage to further assess Heat4 blood levels as a strategy for risk stratification and potential treatment target in HF. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Projektfoerderung im Bereich der Herzmedizin, Leipzig