Coronary artery disease (CAD) is the leading cause of sudden cardiac death in adults, and new methods of predicting disease and risk-stratifying patients will help guide intervention in order to reduce this burden. Current CAD detection involves multiple modalities, but the consideration of other biomarkers will help improve reliability. The aim of this narrative review is to help researchers and clinicians appreciate the growing relevance of miRNA in CAD and its potential as a biomarker, and also to suggest useful miRNA that may be targets for future study. We sourced information from several databases, namely PubMed, Scopus, and Google Scholar, when collating evidentiary information. MicroRNAs (miRNA) are short, noncoding RNAs that are relevant in cardiovascular physiology and pathophysiology, playing roles in cardiac hypertrophy, maintenance of vascular tone, and responses to vascular injury. CAD is associated with changes in miRNA expression profiles, and so are its risk factors, such as abnormal lipid metabolism and inflammation. Thus, they may potentially be biomarkers of CAD. Nevertheless, there are limitations in using miRNA. These include cost and the presence of several confounding factors that may affect miRNA profiles. Furthermore, there is difficulty in the normalisation of miRNA values between published studies, due to pre-analytical variations in samples.

Increases in the prevalence of obesity, insulin resistance, and metabolic syndrome has led to the increase of atrial fibrillation (AF) cases in the developed world. These AF risk factors are associated with mitochondrial dysfunction, previously modelled using peroxisome proliferator activated receptor-γ (PPARγ) coactivator-1 (Pgc-1)-deficient murine cardiac models. We explored gene and protein expression profiles of selected molecular targets related to electrophysiological function in murine Pgc-1α^−/− atria. qPCR analysis surveyed genes related to Na⁺-K⁺-ATPase, K⁺ conductance, hyperpolarisation-activated cyclic nucleotide-gated (Hcn), Na⁺ channels, Ca²⁺ channels, and indicators for adrenergic and cholinergic receptor modulation. Western blot analysis for molecular targets specific to conduction velocity (Na_v1.5 channel and gap junctions) was performed. Transcription profiles revealed downregulation of molecules related to Na⁺-K⁺-ATPase transport, Hcn-dependent pacemaker function, Na⁺ channel-dependent action potential activation and propagation, Ca²⁺ current generation, calsequestrin-2 dependent Ca²⁺ homeostasis, and adrenergic α_1D dependent protection from hypertrophic change. Na_v1.5 channel protein expression but not gap junction expression was reduced in Pgc-1α^−/− atria compared to WT. Na_v1.5 reduction reflects corresponding reduction in its gene expression profile. These changes, as well as the underlying Pgc-1α^−/− alteration, suggest potential pharmacological targets directed towards either upstream PGC-1 signalling mechanisms or downstream ion channel changes.

Despite considerable breakthroughs in Parkinson’s disease (PD) research, understanding of non-motor symptoms (NMS) in PD remains limited. The lack of basic level models that can properly recapitulate PD NMS either in vivo or in vitro complicates matters. Even so, recent research advances have identified cardiovascular NMS as being underestimated in PD. Considering that a cardiovascular phenotype reflects sympathetic autonomic dysregulation, cardiovascular symptoms of PD can play a pivotal role in understanding the pathogenesis of PD. In this study, we have reviewed clinical and non-clinical published papers with four key parameters: cardiovascular disease risks, electrocardiograms (ECG), neurocardiac lesions in PD, and fundamental electrophysiological studies that can be linked to the heart. We have highlighted the points and limitations that the reviewed articles have in common. ECG and pathological reports suggested that PD patients may undergo alterations in neurocardiac regulation. The pathological evidence also suggested that the hearts of PD patients were involved in alpha-synucleinopathy. Finally, there is to date little research available that addresses the electrophysiology of in vitro Parkinson’s disease models. For future reference, research that can integrate cardiac electrophysiology and pathological alterations is required.

The cardiac extracellular matrix (ECM) is involved in several pathological conditions, and age itself is also associated with certain changes in the heart: it gets larger and stiffer, and it develops an increased risk of abnormal intrinsic rhythm. This, therefore, makes conditions such as atrial arrythmia more common. Many of these changes are directly related to the ECM, yet the proteomic composition of the ECM and how it changes with age is not fully resolved. The limited research progress in this field is mainly due to the intrinsic challenges in unravelling tightly bound cardiac proteomic components and also the time-consuming and costly dependency on animal models. This review aims to give an overview of the composition of the cardiac ECM, how different components aid the function of the healthy heart, how the ECM is remodelled and how it is affected by ageing.

Introduction: Ageing and chronic metabolic disorders are associated with mitochondrial dysfunction and cardiac pro-arrhythmic phenotypes which were recently attributed to slowed atrial and ventricular action potential conduction in Pgc-1β^-/- mice. Methods: We compared expression levels of voltage-gated Na_V­1.5 channel and gap junction channels Cx40 and Cx43 in the hearts of young and old, and wild-type (WT) and Pgc-1β^‑/- mice. This employed Western blotting (WB) for Na_V1.5, Cx40 and Cx43 in atrial/ventricular tissue lysates, and immunofluorescence (IF) from Cx43 was explored in tissue sections. Results were analysed using two-way ANOVA for independent/interacting effects of age and genotype. Results: In atria, increased age and Pgc-1β^‑/- genotype each independently decreased both Cx40 and Cx43 expression without interacting effects. In IF experiments, both age and Pgc-1β deletion independently reduced Cx43 expression. In ventricles, age and genotype exerted interacting effects in WB studies of Na_V1.5 expression. Young Pgc-1β^-/- then showed greater Na_V1.5 expression than young WT ventricles. However, neither age nor Pgc-1β deletion affected Cx43 expression, independently or through interacting effects in both WB and IF studies. Conclusion: Similar pro-arrhythmic atrial/ventricular phenotypes arise in aged/Pgc-1β-/- from differing contributions of altered protein expression and functional effects that may arise from multiple acute mechanisms.

Mice deficient in mitochondrial promoter peroxisome proliferator activated receptor-γ co-activator-1β (Pgc-1β^−/−) is a valuable model for metabolic diseases and has been found to present with several pathologies including ventricular arrhythmia. In the present study, our aim was to shed light on the molecular mechanisms behind the observed arrhythmic substrate by studying how the expression of selected genes critical for cardiac function differs in wild-type (WT) compared with Pgc-1β knockout mice and young compared with aged mice. We found that a clear majority of genes are down-regulated in the Pgc-1β^−/− ventricular tissue compared with the WT. Although most individual genes are not significantly differentially expressed, a pattern is apparent when the genes are grouped according to their functional properties. Genes encoding proteins relating to ATPase activity, potassium ion channels relating to repolarisation and resting membrane potential, and genes encoding proteins in the cAMP pathway are found to be significantly down-regulated in the Pgc-1β deficient mice. On the contrary, the pacemaker channel genes Hcn3 and Hcn4 are up-regulated in subsets of the Pgc-1β deficient tissue. Furthermore, we found that with age, especially in the Pgc-1β^−/− genotype, most genes are up-regulated including genes relating to the resting membrane potential, calcium homeostasis, the cAMP pathway, and most of the tested adrenoceptors. In conclusion, we here demonstrate how a complex pattern of many modest changes at gene level may explain major functional differences of the action potential related to ageing and mitochondrial dysfunction.