AI Article Synopsis
- Capillary endothelial cells play a role in heart growth and function under stress, but their exact impact on heart failure is unclear.
- The transcription factor GATA2 is found to be reduced in hearts with failure, and mice lacking GATA2 in endothelial cells develop heart failure and disrupted signaling during stress.
- Two long non-coding RNAs (GADLOR1 and GADLOR2) produced by endothelial cells are identified as key players that transfer to heart muscle cells, blocking normal stress responses and possibly contributing to heart disease.
Article Abstract
Capillary endothelial cells modulate myocardial growth and function during pathological stress, but it is unknown how and whether this contributes to the development of heart failure. We found that the endothelial cell transcription factor GATA2 is downregulated in human failing myocardium. Endothelial GATA2 knock-out (G2-EC-KO) mice develop heart failure and defective myocardial signal transduction during pressure overload, indicating that the GATA2 downregulation is maladaptive. Heart failure and perturbed signaling in G2-EC-KO mice could be induced by strong upregulation of two unknown, endothelial cell-derived long non-coding (lnc) RNAs (AK037972, AK038629, termed here GADLOR1 and 2). Mechanistically, the GADLOR1/2 lncRNAs transfer from endothelial cells to cardiomyocytes, where they block stress-induced signalling. Thereby, lncRNAs can contribute to disease as paracrine effectors of signal transduction and therefore might serve as therapeutic targets in the future.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9775420 | PMC |
| http://dx.doi.org/10.3390/biology11121736 | DOI Listing |
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