Circulating CCRR serves as potential novel biomarker for predicting acute myocardial infarction

Objective:Cold regions exhibit a high prevalence of cardiovascular disease,particularly acute myocardial infarction(AMI),which is one of the leading causes of death associated with cardiovascular conditions.Cardiovascular disease is closely linked to the abnormal expression of long non-coding RNA(lncRNA).This study investigates whether circulating levels of lncRNA cardiac conduction regulatory RNA(CCRR)could serve as a biomarker for AMI.Materials and methods:We measured circulating CCRR from whole blood samples collected from 68 AMI patients and 69 non-AMI subjects.An AMI model was established using C57BL/6 mice.Quantitative reverse transcription PCR(qRT-PCR)was used to assess CCRR expression.Exosomes were isolated from cardiomyocytes,and their characteristics were evaluated using electron microscope and nanoparticle tracking analysis.The exosome inhibitor GW4869 was employed to examine the effect of exosomal CCRR on cardiac function using echocardiography.Protein expression was detected using Western blot and immunofluorescence staining.Results:The circulating level of CCRR was significantly higher in AMI patients(1.93±0.13)than in non-AMI subjects(1.00±0.05,P<0.001).The area under the ROC curve(AUC)of circulating CCRR was 0.821.Similar changes in circulating CCRR levels were consistently observed in an AMI mouse model.Exosomal CCRR derived from hypoxia-induced cardiomyocytes and cardiac tissue after AMI were increased,a change that was reversed by GW4869.Additionally,CCRR-overexpressing exosomes improved cardiac function in AMI.Conclusion:Circulating lncRNA CCRR is a potential predictor of AMI.Exosomal CCRR plays a role in the communication between the heart and other organs through circulation.

LncRNA CCRR maintains Ca^(2+)homeostasis against myocardial infarction through the FTO-SERCA2a pathway

Cardiac conduction regulatory RNA(CCRR)has been documented as an antiarrhythmic lncRNA in our earlier investigation.This study aimed to evaluate the effects of CCRR on SERCA2a and the associated Ca^(2+)homeostasis in myocardial infarction(MI).Overexpression of CCRR via AAV9-mediated delivery not only partially reversed ischemia-induced contractile dysfunction but also alleviated abnormal Ca^(2+)homeostasis and reduced the heightened methylation level of SERCA2a following MI.These effects were also observed in CCRR overexpressing transgenic mice.A conserved sequence domain of CCRR mimicked the protective function observed with the full length.Furthermore,silencing CCRR in healthy mice led to intracellular Ca^(2+)overloading of cardiomyocytes.CCRR increased SERCA2a protein stability by upregulating FTO expression.The direct interaction between CCRR and FTO protein was characterized by RNA-binding protein immunoprecipitation(RIP)analysis and RNA pulldown experiments.Activation of NFATc3 was identified as an upstream mechanism responsible for CCRR downregulation in MI.This study demonstrates that CCRR is a protective lncRNA that acts by maintaining the function of FTO,thereby reducing the m^(6)A RNA methylation level of SERCA2a,ultimately preserving calcium homeostasis for myocardial contractile function in MI.Therefore,CCRR may be considered a promising therapeutic strategy with a beneficial role in cardiac pathology.