Chronic heart failure is associated with adverse remodeling of the heart that is typically characterized by cardiomyocyte hypertrophy. This requires the formation of new capillaries to maintain oxygen supply. Insufficient angiogenesis promotes the transition from compensated hypertrophy into heart failure.
We isolated left ventricular endothelial cells from patients with advanced heart failure undergoing left ventricular assist device surgery (n = 15) and healthy organ donors (n = 2) and performed RNA sequencing. In a weighted coexpression network analysis, we identified the transcription factors CASZ1, ZNF523, and NFE2L1 as hub genes of a cluster related to angiogenesis. Knock-down of CASZ1, ZNF523, or NFE2L1 in human umbilical vein endothelial cells led to a downregulation of genes from the respective cluster, including CD34 and platelet derived growth factor β, confirming their regulatory function.
Wirth L, Erny E, Krane M, Lahm H, Hein L, Gilsbach R, Lother A. Gene expression networks in endothelial cells from failing human hearts.
Am J Physiol Heart Circ Physiol. 2024. PMID: 39028282