Epicardial adipose tissue (EAT) is a unique fat depot located between the myocardium and the visceral layer of pericardium. It can be further subdivided into pericoronary (PCAT), periatrial (PAAT) and periventricular adipose tissue (PVentAT), each of them exhibiting specific characteristics and association with the underlying tissue. Since no physical barrier separates EAT from the myocardium, this fat tissue can easily interact with the underlying cardiac structure. EAT can be visualized using various imaging modalities. Computed tomography provides not only information on EAT volume, but also on its density. Indeed, EAT density reflected by the recently developed fat attenuation index (FAI) is emerging as a useful index of PCAT inflammation, PAAT inflammation and fibrosis, while the relevance of density of PVentAT is much less known. The emerging data indicates that FAI can be an important diagnostic and prognostic tool in both coronary artery disease and atrial fibrillation. Future studies will demonstrate if it also could be used as a marker of efficacy of therapies and whether FAI PVentAT could indicate ventricular pathologies, such as heart failure. The aim of the review is to present computed tomography derived FAI as an important tool both to study and better understand the epicardial fat and as a potential predictive marker in cardiovascular disorders.

Myocardial infarction (MI) is a leading cause of maladaptive cardiac remodeling and heart failure. In the damaged heart, loss of function is mainly due to cardiomyocyte death and remodeling of the cardiac tissue. The current study shows that A-kinase anchoring protein 2 (AKAP2) orchestrates cellular processes favoring cardioprotection in infarcted hearts. Induction of AKAP2 knockout (KO) in cardiomyocytes of adult mice increases infarct size and exacerbates cardiac dysfunction after MI, as visualized by increased left ventricular dilation and reduced fractional shortening and ejection fraction. In cardiomyocytes, AKAP2 forms a signaling complex with PKA and the steroid receptor co-activator 3 (Src3). Upon activation of cAMP signaling, the AKAP2/PKA/Src3 complex favors PKA-mediated phosphorylation and activation of estrogen receptor α (ERα). This results in the upregulation of ER-dependent genes involved in protection against apoptosis and angiogenesis, including Bcl2 and the vascular endothelial growth factor a (VEGFa). In line with these findings, cardiomyocyte-specific AKAP2 KO reduces Bcl2 and VEGFa expression, increases myocardial apoptosis and impairs the formation of new blood vessels in infarcted hearts. Collectively, our findings suggest that AKAP2 organizes a transcriptional complex that mediates pro-angiogenic and anti-apoptotic responses that protect infarcted hearts.

Development of heart failure (HF) after myocardial infarction (MI) is responsible for premature death. Complex cellular and molecular mechanisms are involved in this process. A number of studies have linked the epitranscriptomic RNA modification N6-methyladenosine (m6A) with HF, but it remains unknown how m6A affects the risk of developing HF after MI. We addressed the regulation of m6A and its demethylase fat mass and obesity-associated (FTO) after MI and their association with HF. Using liquid chromatography coupled to mass spectrometry, we observed an increase of m6A content in the infarcted area of rat hearts subjected to coronary ligation and a decrease in blood. FTO expression measured by quantitative PCR was downregulated in the infarcted hearts. In whole blood samples collected at the time of reperfusion in MI patients, m6A content was lower in patients who developed HF as attested by a 4-month ejection fraction (EF) of ≤40% as compared to patients who did not develop HF (EF > 50%). M6A content was higher in females. These results show that m6A measured in blood is associated with HF development after MI and motivate further investigation of the potential role of m6A as a novel epitranscriptomics biomarker and therapeutic target of HF.