Peripheral Blood RNA Levels of QSOX1 and PLBD1 are New Independent Predictors of Left Ventricular Dysfunction after Acute Myocardial Infarction

November 22, 2019

Background – The identification of patients with acute myocardial infarction (MI) at risk of subsequent left ventricular (LV) dysfunction remains challenging, but it is important to optimize therapies. The aim of this study was to determine the unbiased RNA profile in peripheral blood of patients with acute MI and to identify and validate new prognostic markers of LV dysfunction. Methods – We prospectively enrolled a discovery cohort with acute MI (n=143) and performed whole blood RNA profiling at different time points. We then selected transcripts on admission that related to LV dysfunction at follow-up and validated them by quantitative polymerase chain reaction (qPCR) in the discovery cohort, in an external validation cohort (n=449) and in a representative porcine MI model with cardiac magnetic resonance-based measurements of infarct size and postmortem myocardial pathology (n=33). Results – RNA profiling in the discovery cohort showed upregulation of genes involved in chemotaxis, interleukin-6 and NF-κB signaling in the acute phase of MI. Expression levels of the majority of these transcripts paralleled the rise in cardiac troponin T and decayed at 30 days. RNA levels of QSOX1, PLBD1 and S100A8 on admission with MI correlated with LV dysfunction at follow-up. Using qPCR, we confirmed that QSOX1 and PLBD1 predicted LV dysfunction (OR 2.6 [95% CI 1.1-6.1] and 3.2 [1.4-7.4]) whereas S100A8 did not. In the external validation cohort, we confirmed QSOX1 and PLBD1 as new independent markers of LV dysfunction (OR 1.41 [1.06-1.88] and 1.43 [1.08-1.89]). QSOX1 had an incremental predictive value in a model consisting of clinical variables and cardiac biomarkers (including NT-ProBNP). In the porcine MI model, whole blood levels of QSOX1 and PLBD1 related to neutrophil infiltration in the ischemic myocardium in an infarct size-independent manner. Conclusions – Peripheral blood QSOX1 and PLBD1 in acute MI are new independent markers of LV dysfunction post-MI.

Long Noncoding Competing Endogenous RNA Networks in Age-Associated Cardiovascular Diseases

June 24, 2019

Abstract: Cardiovascular diseases (CVDs) are the most serious health problem in the world, displaying high rates of morbidity and mortality. One of the main risk factors for CVDs is age. Indeed, several mechanisms are at play during aging, determining the functional decline of the cardiovascular system. Aging cells and tissues are characterized by diminished autophagy, causing the accumulation of damaged proteins and mitochondria, as well as by increased levels of oxidative stress, apoptosis, senescence and inflammation. These processes can induce a rapid deterioration of cellular quality-control systems. However, the molecular mechanisms of age-associated CVDs are only partially known, hampering the development of novel therapeutic strategies. Evidence has emerged indicating that noncoding RNAs (ncRNAs), such as long ncRNAs (lncRNAs) and microRNAs (miRNAs), are implicated in most patho-physiological mechanisms. Specifically, lncRNAs can bind miRNAs and act as competing endogenous-RNAs (ceRNAs), therefore modulating the levels of the mRNAs targeted by the sponged miRNA. These complex lncRNA/miRNA/mRNA networks, by regulating autophagy, apoptosis, necrosis, senescence and inflammation, play a crucial role in the development of age-dependent CVDs. In this review, the emerging knowledge on lncRNA/miRNA/mRNA networks will be summarized and the way in which they influence age-related CVDs development will be discussed.