Fig. 1

The mechanisms of cardiac injury caused by SARS-CoV-2. a Dotplot representing the relative expression of ACE2 and TMPRSS2 in the heart. Public single-nucleus RNA sequencing (snRNA-seq) data from the Genome Sequence Archive database (CRA002689) were used for bioinformatics analysis. b KEGG pathway enrichment analysis shows the pathways associated with TMPRSS2-expressing cells. c SARS-CoV-2 was visualized by RNA in-situ hybridization in the SARS-CoV-2 infection rhesus macaques. HE staining in the left. Positive strand SARS-CoV-2 was detected by probes labeled with green fluorescence. The antisense strand of SARS-CoV-2 was detected with probe labeled with red fluorescence, indicating the replication of virus (Scale bar = 50 μm). d Representative views of HE staining of the left ventricle. To simulate respiratory tract infection, rhesus macaques in SARS-CoV-2 group were intratracheally challenged with SARS-CoV-2 at 50% TCID50 of 1 × 10⁶. The arrow indicates the infiltration of inflammatory cells in SARS-CoV-2 group. (N = 6 in each group, Scale bar = 50 μm). e Representative immunohistochemical staining for CD3, CD68, IL-6, IL-1β, IL-18, TNF-α, and IFN-γ of the left ventricles and quantification of staining positive areas. (N = 6 in each group, Scale bar = 50 μm). f Representative images of Masson staining in the left ventricles of the two groups. (N = 6 in each group, Scale bar = 50 μm). g Representative views of HE staining of the left ventricle. The arrow indicates a micro-thrombus in SARS-CoV-2 group. h Representative immunohistochemical staining for TM and VE-cadherin of microvascular in the left ventricles. (TM: n = 3 in each group; VE-cadherin: n = 5 in control group, n = 4 in SARS-CoV-2 group, Scale bar = 50 μm). i Representative western blots showing TM and VE-cadherin protein expression in the two groups (N = 3 in each group). Protein levels were normalized to GAPDH protein. (N = 4 in control group, n = 6 in SARS-CoV-2 group). All data are presented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. The unpaired two-tailed student’s t-test was used to assess differences between the two groups. EC endothelial cells, SMC smooth muscle cells, CCS cardiac conduction system cell, HE hematoxylin and eosin, TCID50 tissue-culture infectious doses, TM thrombomodulin