Progress in cardiac research: from rebooting cardiac regeneration to a complete cell atlas of the heart

Abstract

We review some of the important discoveries and advances made in basic and translational cardiac research in 2020. For example, in the field of myocardial infarction (MI), new aspects of autophagy and the importance of eosinophils were described. Novel approaches such as a glycocalyx mimetic were used to improve cardiac recovery following MI. The strategy of 3D bio-printing was shown to allow the fabrication of a chambered cardiac organoid. The benefit of combining tissue engineering with paracrine therapy to heal injured myocardium is discussed. We highlight the importance of cell-to cell communication, in particular the relevance of extracellular vesicles such as exosomes, which transport proteins, lipids, non-coding RNAs and mRNAs and actively contribute to angiogenesis and myocardial regeneration. In this rapidly growing field, new strategies were developed to stimulate the release of reparative exosomes in ischaemic myocardium. Single-cell sequencing technology is causing a revolution in the study of transcriptional expression at cellular resolution, revealing unanticipated heterogeneity within cardiomyocytes, pericytes and fibroblasts, and revealing a unique subpopulation of cardiac fibroblasts. Several studies demonstrated that exosome- and non-coding RNA-mediated approaches can enhance human induced pluripotent stem cell (iPSC) viability and differentiation into mature cardiomyocytes. Important details of the mitochondrial Ca2+ uniporter and its relevance were elucidated. Novel aspects of cancer therapeutic-induced cardiotoxicity were described, such as the novel circular RNA circITCH, which may lead to novel treatments. Finally, we provide some insights into the effects of SARS-CoV-2 on the heart.

Manifestations and Mechanism of SARS-CoV2 Mediated Cardiac Injury

“…In addition, the reduction of ACE2 will increase ROS generation due to enhanced NADPH activity and reduce mitochondrial homeostasis. A recent study of genome-wide transcriptional alterations induced by SARS-CoV-2 infection in IPSC-CMs had revealed that genes involved in mitochondrial function and energy production were downregulated, indicating that SARS-CoV-2 might promote a shift toward a glycolytic metabolism by suppressing mitochondrial oxidative phosphorylation, which could also favor its replication 68 . Owing to the excessive production of ROS in the heart, a potential anti-oxidative therapy had been suggested to alleviate cardiogenic casualties caused by COVID-19.…”

Application of hiPSC as a Drug Tester Via Mimicking a Personalized Mini Heart

“…During the worldwide outbreak of COVID-19, the hIPSC-CM-EHT model has contributed to several types of investigations that: 1) mimicked myocardial injuries caused by SARS-CoV-2 infection ( Li et al, 2021 ; Perez-Bermejo et al, 2021 ; Salerno et al, 2021 ; Xie et al, 2022 ); 2) evaluated the safety of different types of vaccines including mRNA and adenovirus vaccines, especially across different ethnic populations with different genomic backgrounds ( Bojkova et al, 2020 ; Lu et al, 2020 ; Davidson et al, 2021 ); and 3) assessed the potential side effects of anti-COVID-19 developed treatments on cardiomyocytes ( Charrez et al, 2021 ; Deguchi et al, 2021 ; Dimai et al, 2021 ). Research involving the hIPSC-CM-EHT model in COVID-19 has rapidly extended the application of hIPSC, making it a more common conceptual and powerful investigative tool.…”

Comprehension of the Relationship between Autophagy and Reactive Oxygen Species for Superior Cancer Therapy with Histone Deacetylase Inhibitors

“…Autophagy also plays a key role in other diseases including obesity and diabetes, cardiovascular disease, and bacterial infections [87]. For the treatment of those diseases, single-cell studies would be valuable in optimizing the treatment's efficacy [88,89]. While comparable to apoptosis, autophagy is engaged to intricate signaling pathways even to cell survival.…”