International Journal of Molecular Sciences Editorial y RNAs in Brain and Heart Diseases Dimitris Beis 1 , Inga Zerr 2 , Fabio Martelli 3 , Wolfram Doehner 4 and Yvan Devaux 5,* 1 Zebrafish Disease Models lab, Center for Experimental Surgery Clinical and Translational Research, Biomedical Research Foundation Academy of Athens, 11527 Athens, Greece; [email protected] 2 Department of Neurology, Clinical Dementia Centre and DZNE, University Medical School, Georg-August University, 37075 Göttingen, Germany; [email protected] 3 Molecular Cardiology Laboratory, IRCCS Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy; [email protected] 4 Department of Cardiology (Virchow Klinikum), BIH-Center for Regenerative Therapies, and Center for Stroke Research Berlin Charité-Universitätsmedizin, 13353 Berlin, Germany; [email protected] 5 Cardiovascular Research Unit, Department of Population Health, Luxembourg Institute of Health, L-1445 Strassen, Luxembourg * Correspondence: [email protected]; Tel.: +352-26970300 On behalf of the EU-CardioRNA COST Action CA17129. y Received: 12 May 2020; Accepted: 19 May 2020; Published: 25 May 2020 Abstract: In the era of single-cell analysis, one always has to keep in mind the systemic nature of various diseases and how these diseases could be optimally studied. Comorbidities of the heart in neurological diseases as well as of the brain in cardiovascular diseases are prevalent, but how interactions in the brain–heart axis affect disease development and progression has been poorly addressed. Several brain and heart diseases share common risk factors. A better understanding of the brain–heart interactions will provide better insights for future treatment and personalization of healthcare, for heart failure patients’ benefit notably. We review here emerging evidence that studying noncoding RNAs in the brain–heart axis could be pivotal in understanding these interactions. We also introduce the Special Issue of the International Journal of Molecular Sciences RNAs in Brain and Heart Diseases—EU-CardioRNA COST Action. Keywords: brain; heart; comorbidities; noncoding RNAs; neurocardiology 1. Introduction The concept of “Neurocardiology”, although known since the early 1980s [1], is re-emerging. Epidemiological data link psychosocial stress to cardiovascular disease [2]. Low socioeconomic status induces stress to the brain through chronic activation of the amygdala, leading to activation of inflammation, enhanced atherogenesis, and cardiovascular events [3]. 2. Physiological Interactions between the Heart and Brain Neurodegenerative diseases share risk factors with cardiovascular diseases, such as age, high blood pressure, sex, high cholesterol, and presence of amyloid oligomers [4]. Mutations in the β-secretase-1 gene lead to β-amyloid peptide accumulation and chronic inflammation [4,5]. Alzheimer’s disease (AD) patients show diastolic dysfunction and other cardiac functional defects reminiscent of cardiac amyloidosis [6,7]. On the other side, ischemic heart failure patients display increased left-ventricular levels of both β-secretase-1 (BACE1) and β-amyloid peptides, as well as the noncoding RNA antisense transcript BACE1-AS [8], suggesting common pathogenetic mechanisms with Alzheimer’s disease. Moreover, increased β-amyloid plasma levels allow identifying patients at high risk for cardiovascular death [9]. Therefore, compromised myocardial function and intramyocardial deposits of Aβ have Int. J. Mol. Sci. 2020, 21, 3717; doi:10.3390/ijms21103717 www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2020, 21, 3717 2 of 6 Int. J. Mol. Sci. 2020, 21, x FOR PEER REVIEW 2 of 6 been reported in AD patients and suggestions are made that AD may be viewed rather as a systemic mainlydisease damage [6–9]. 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In including patients theresuscitated heart and thefrom pancreas, cardiac reviewed arrest, higher in [16]. heartbeat-evokedIn patients resuscitated brain from potentials, cardiac arrest,as recorded higher heartbeat-evoked by electroencephalographic brain potentials, combined as recorded with by electrocardiographicelectroencephalographic assessment, combined are with associated electrocardiographic with a higher assessment, survival at aresix associatedmonths [17]. with However, a higher adrenalinesurvival at administration six months [17 to]. However,restart the adrenalineheart was associated administration with more to restart severe the neurological heart was associatedproblems [18].with moreBoth severecardiac neurological damage and problems brain [injury18]. Both elicit cardiac an damageinitially andlocal brain and injury ultimately elicit an systemic initially inflammatorylocal and ultimately response systemic that affects inflammatory multiple responseorgans. 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NoncodingNoncoding RNAs RNAs as Potential are a relatively Long-Distance recently Signal described Mediators but significant and Circulating subpopulation Biomarkers of the transcriptome that emerged following the latest developments in next-generation sequencing Noncoding RNAs are a relatively recently described but significant subpopulation of the technologies. A large proportion of these molecules are tissue- and developmental-stage-specific, transcriptome that