Single-cell Sequencing Of Heart Failure With Preserved Ejection Fraction

Background Heart failure(HF)is the common end stage of many heart structural dysfunction with various causes which has become the global public health issue.In elderly people(age>60),the morbidity surpasses 2%,and among which the heart failure with preserved ejection fraction(HFpEF)is more general.The pathophysiological process of HFpEF is unclear,and lack of comprehensive animal model.Therefore there are no enough therapies for HFpEF.Besides cardiomyocytes,other noncardiac cells,mainly endothelia and fibroblasts are also playing important roles over the progress of HFpEF.This article applies the latest animal model to seek the potential key noncardiac cells.This will lay a theoretical foundation for the therapy targets and future research.Methods 1.Build the animal model of HFpEF with a combination of high fat diet and L-NAME.2.Prove the validity of the animal model by echocardiography,exercise test,lung function test and pathology.3.With the result of single-cell sequencing,analyze the difference of cells distribution between the control groups and experiment groups.4.With the result of single-cell sequencing,analyze the subgroups of endothelia and fibroblasts.Results 1.After taking the high fat diet and L-NAME for 5 weeks,the mouse has weak left ventricle relaxation,exaggerated lung congestion,cardiomyocytes hypertrophy and cardiac fibrosis.2.The single-cell sequencing manifests that the number of endothelial and fibroblasts changes in HFpEF.Among the subgroups of endothelial,Cardiomyocyte ECs increase;among the subgroups of fibroblasts,F-Act2 increase.Conclusion Endothelial and fibroblasts play crucial roles in the development of HFpEF.Cardiomyocyte ECs increase to protect the contraction of heart,yet F-Act2 mediate the cardiac fibrosis and collagen deposition.