Objective  In March 2022, more than 600 million cases of Corona Virus Disease 2019 (COVID-19) and about 6 million deaths have been reported worldwide. Unfortunately, while effective antiviral therapy has not yet been available, chloroquine (CQ)/hydroxychloroquine (HCQ) has been considered an option for the treatment of COVID-19. While many studies have demonstrated the potential of HCQ to decrease viral load and rescue patients' lives, controversial results have also been reported. One concern associated with HCQ in its clinical application to COVID-19 patients is the potential of causing long QT interval (LQT), an electrophysiological substrate for the induction of lethal ventricular tachyarrhythmias. Yet, the mechanisms for this cardiotoxicity of HCQ remained incompletely understood.  Materials and methods  Adult New Zealand white rabbits were used for investigating the effects of HCQ on cardiac electrophysiology and expression of ion channel genes. HEK-293T cells with sustained overexpression of human-ether-a-go-go-related gene (hERG) K⁺ channels were used for whole-cell patch-clamp recordings of hERG K⁺ channel current (I_hERG). Quantitative RT-PCR analysis and Western blot analysis were employed to determine the expression of various genes at mRNA and protein levels, respectively.  Results  electrocardiogram (ECG) recordings revealed that HCQ prolonged QT and RR intervals and slowed heart rate in rabbits. Whole-cell patch-clamp results showed that HCQ inhibited the tail current of hERG channels and slowed the reactivation process from inactivation state. HCQ suppressed the expression of hERG and hindered the formation of the heat shock protein 90 (Hsp90)/hERG complex. Moreover, the expression levels of connexin 43 (CX43) and Kir2.1, the critical molecular/ionic determinants of cardiac conduction thereby ventricular arrythmias, were decreased by HCQ, while those of Cav1.2, the main Ca²⁺ handling proteins, remained unchanged and SERCA2a was increased.  Conclusion  HCQ could induce LQT but did not induce arrhythmias, and whether it is suitable for the treatment of COVID-19 requires more rigorous investigations and validations in the future.

  Objective  Long noncoding RNAs (lncRNAs) play an important role in regulating the occurrence and development of cardiovascular diseases. However, the role of lncRNAs in heart aging remains poorly understood. The objective of this study was to identify differentially expressed lncRNAs in the heart of aging mice and elucidate the relevant regulatory pathways of cardiac aging.  Materials and methods  Echocardiography was used to detect the cardiac function of 18-months (aged) and 3-months (young) old C57BL/6 mice. Microarray analysis was performed to unravel the expression profiles of lncRNAs and mRNAs, and qRT-PCR to verify the highly dysregulated lncRNAs.  Results  Our results demonstrated that the heart function in aged mice was impaired relative to young ones. Microarray results showed that 155 lncRNAs were upregulated and 37 were downregulated, and 170 mRNAs were significantly upregulated and 44 were remarkably downregulated in aging hearts. Gene ontology analysis indicated that differentially expressed genes are mainly related to immune function, cell proliferation, copper ion response, and cellular cation homeostasis. KEGG pathway analysis showed that the differentially expressed mRNAs are related to cytokine-cytokine receptor interaction, inflammatory mediator regulation of TRP channels, and the NF-kappa B signaling pathway.  Conclusion  These results imply that the differentially expressed lncRNAs may regulate the development of heart aging. This study provides a new perspective on the potential effects and mechanisms of lncRNAs in heart aging.

Hypertension is the most common cardiovascular condition in clinical practice and a major risk factor for stroke and cardiovascular events. There are more than 270 million hypertension patients in China, and the prevalence of hypertension in the high-latitude cold areas is significantly higher than in the low-latitude warm areas. The unique epidemiological characteristics and risk factors of hypertension in the cold regions of China urge for establishment of the prevention and control system for targeted and more effective management of the condition.