BACKGROUND: The epidemiologic and clinical characteristics of heart transplant (HTx) recipients during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic remains unclear. We studied the characteristics of HTx recipients from December 20, 2019, to February 25, 2020, in an effort to understand their risk and outcomes. METHODS: All accessible HTx recipients were included in this single-center retrospective study. We collected information on the recipients using a web-based questionnaire as well as the hospital database. RESULTS: We followed 87 HTx recipients (72.4% were men, and the average age was 51 years). A total of 79 recipients resided in Hubei, and 57 recipients had a Wuhan-related history of travel or contact. Most took precautionary measures while in contact with suspicious crowds, and 96.6% of the families and communities undertook prevention and quarantine procedures. Four upper airway infections were reported, and 3 of them tested negative for SARS-CoV-2 (the fourth recovered and was not tested). All cases were mild and successfully recovered after proper treatment. Laboratory results of 47 HTx cases within the last 2 months were extracted. Of these, 21.3% of recipients had pre-existing lymphopenia, and 87.2% of recipients had a therapeutic concentration of tacrolimus (5−12 ng/ml). Liver and kidney insufficiency was seen in 5 and 6 recipients, respectively. CONCLUSION: HTx recipients who practiced appropriate prevention measures had a low rate of infection with SARS-CoV-2 and transition to the associated disease COVID-19. These early data will require confirmation as the pandemic establishes around the world.

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) was closely involved in doxorubicin- (DOX-) induced cardiotoxicity. MicroRNA-200a (miR-200a) could target Keap1 mRNA and promote degradation of Keap1 mRNA, resulting in Nrf2 activation. However, the role of miR-200a in DOX-related cardiotoxicity remained unclear. Our study is aimed at investigating the effect of miR-200a on DOX-induced cardiotoxicity in mice. For cardiotropic expression, male mice received an injection of an adeno-associated virus 9 (AAV9) system carrying miR-200a or miR-scramble. Four weeks later, mice received a single intraperitoneal injection of DOX at 15 mg/kg. In our study, we found that miR-200a mRNA was the only microRNA that was significantly decreased in DOX-treated mice and H9c2 cells. miR-200a supplementation blocked whole-body wasting and heart atrophy caused by acute DOX injection, decreased the levels of cardiac troponin I and the N-terminal probrain natriuretic peptide, and improved cardiac and adult cardiomyocyte contractile function. Moreover, miR-200a reduced oxidative stress and cardiac apoptosis without affecting matrix metalloproteinase and inflammatory factors in mice with acute DOX injection. miR-200a also attenuated DOX-induced oxidative injury and cell loss in vitro. As expected, we found that miR-200a activated Nrf2 and Nrf2 deficiency abolished the protection provided by miR-200a supplementation in mice. miR-200a also provided cardiac benefits in a chronic model of DOX-induced cardiotoxicity. In conclusion, miR-200a protected against DOX-induced cardiotoxicity via activation of the Nrf2 signaling pathway. Our data suggest that miR-200a may represent a new cardioprotective strategy against DOX-induced cardiotoxicity.

Both matrix metalloproteinase-9 (MMP9) and transforming growth factors-β1 (TGF-β1) are the important factors in the pathogenesis of the aortic aneurysm (AA) and aortic dissection (AD). Recent studies have shown that inhibition of reactive oxygen species (ROS) production, extracellular signal-regulated kinase 1/2(ERK1/2) or NF-κB pathways is able to suppress aneurysm formation. The median layers of arterial walls are mainly the vascular smooth muscle cells (VSMCs), while the pathogenesis of AA and AD is closely related to the changes in the median layer structure. Thus, we investigated the molecular mechanisms underlying TGF-β1-induced MMP-9 expression in VSMC, the involvement of intracellular ROS and signaling molecules, including ERK1/2 and NF-κB. Rat vascular smooth muscle cells (A7r5) were used. MMP-9 expression was analyzed by gelatin zymography, western blot and RT-PCR. The involvement of intracellular ROS and signaling molecules including ERK1/2 and NF-κB in the responses was investigated using reactive oxygen scavenger N-acetylcysteine (NAC) and pharmacological inhibitors (U0126 and BAY11-7082), determined by ROS testing and western blot testing for their corresponding proteins. TGF-β1 induces MMP-9 expression via ROS-dependent signaling pathway. ROS production leads to activation of ERK1/2 and then activation of the NF-κB transcription factor. Activated NF-κB turns on transcription of the MMP-9 gene. The process in which TGF-β1 induces MMP9 expression involves the ROS-dependent ERK-NF-κB signal pathways in VSMC. This discovery raises a new regulation pathway in the VSMC, and it shows the potential to help to find a new solution to treating aortic aneurysm and aortic dissection.

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