Endocardial/endothelial angiocrines regulate cardiomyocyte development and maturation and induce features of ventricular non-compaction.

Autor:	Rhee S; Department of Biology, Stanford University, Stanford, CA 94305, USA., Paik DT; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.; Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Yang JY; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.; Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Nagelberg D; Department of Biology, Stanford University, Stanford, CA 94305, USA., Williams I; Department of Biology, Stanford University, Stanford, CA 94305, USA.; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA., Tian L; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.; Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Roth R; Department of Biology, Stanford University, Stanford, CA 94305, USA., Chandy M; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.; Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Ban J; Department of Biology, Stanford University, Stanford, CA 94305, USA., Belbachir N; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.; Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Kim S; Department of Developmental Biology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA., Zhang H; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.; Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Phansalkar R; Department of Genetics, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA., Wong KM; Department of Biology, Stanford University, Stanford, CA 94305, USA., King DA; Department of Biology, Stanford University, Stanford, CA 94305, USA., Valdez C; Department of Biology, Stanford University, Stanford, CA 94305, USA., Winn VD; Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA., Morrison AJ; Department of Biology, Stanford University, Stanford, CA 94305, USA., Wu JC; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.; Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Red-Horse K; Department of Biology, Stanford University, Stanford, CA 94305, USA.; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jazyk:	angličtina
Zdroj:	European heart journal [Eur Heart J] 2021 Nov 01; Vol. 42 (41), pp. 4264-4276.
DOI:	10.1093/eurheartj/ehab298
Abstrakt:	Aims: Non-compaction cardiomyopathy is a devastating genetic disease caused by insufficient consolidation of ventricular wall muscle that can result in inadequate cardiac performance. Despite being the third most common cardiomyopathy, the mechanisms underlying the disease, including the cell types involved, are poorly understood. We have previously shown that endothelial cell-specific deletion of the chromatin remodeller gene Ino80 results in defective coronary vessel development that leads to ventricular non-compaction in embryonic mouse hearts. We aimed to identify candidate angiocrines expressed by endocardial and endothelial cells (ECs) in wildtype and LVNC conditions in Tie2Cre;Ino80fl/fltransgenic embryonic mouse hearts, and test the effect of these candidates on cardiomyocyte proliferation and maturation. Methods and Results: We used single-cell RNA-sequencing to characterize endothelial and endocardial defects in Ino80-deficient hearts. We observed a pathological endocardial cell population in the non-compacted hearts and identified multiple dysregulated angiocrine factors that dramatically affected cardiomyocyte behaviour. We identified Col15a1 as a coronary vessel-secreted angiocrine factor, downregulated by Ino80-deficiency, that functioned to promote cardiomyocyte proliferation. Furthermore, mutant endocardial and endothelial cells up-regulated expression of secreted factors, such as Tgfbi, Igfbp3, Isg15, and Adm, which decreased cardiomyocyte proliferation and increased maturation. Conclusions: These findings support a model where coronary endothelial cells normally promote myocardial compaction through secreted factors, but that endocardial and endothelial cells can secrete factors that contribute to non-compaction under pathological conditions. (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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