State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China
Kaiyi Zhang
State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China
Yu Yang
State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China
Shuang Xu
State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China
Juan Du
State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China
Tianwen Wu
State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China
Cong Tao
State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China
Yanfang Wang
State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China; Corresponding author
Shulin Yang
State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China; Corresponding author
Summary: Cardiac damage is widely present in patients with metabolic diseases, but the exact pathophysiological mechanisms involved remain unclear. The porcine heart is an ideal material for cardiovascular research due to its similarities to the human heart. This study evaluated pathological features and performed single-nucleus RNA sequencing (snRNA-seq) on myocardial samples from both wild-type and metabolic disease-susceptible transgenic pigs (previously established). We found that transgenic pigs exhibited lipid metabolism disturbances and myocardial injury after a high-fat high-sucrose diet intervention. snRNA-seq reveals the cellular landscape of healthy and metabolically disturbed pig hearts and identifies the major cardiac cell populations affected by metabolic diseases. Within metabolic disorder hearts, metabolically active cardiomyocytes exhibited impaired function and reduced abundance. Moreover, massive numbers of reparative LYVE1+ macrophages were lost. Additionally, proinflammatory endothelial cells were activated with high expression of multiple proinflammatory cytokines. Our findings provide insights into the cellular mechanisms of metabolic disease-induced myocardial injury.
