Loss of endothelial miR-143/145 accelerates vascular senescence and diastolic cardiac dysfunction

ABSTRACT: Age‑associated vascular remodelling critically contributes to cardiac dysfunction, yet the molecular drivers of cardiac vascular senescence remain incompletely understood. Here, we describe a novel function of the miR-143/145 cluster in cardiac endothelial cells. Global deletion of miR‑143/145 in mice induces profound vascular senescence in cardiac arteries and the microvasculature, implicating loss of miR‑145 as a key trigger of vascular ageing. Surprisingly, endothelial‑specific, but not vascular smooth muscle cell‑specific, miR‑143/145 deletion causes diastolic dysfunction, left atrial enlargement, and marked senescence. In vitro, miR‑145‑5p inhibition elicits EC senescence with impaired proliferation and migration, in part through de-repression of the downstream target SERPINE1, whose

INSTRUMENT(S): NextSeq 2000

ORGANISM(S): Homo sapiens

SUBMITTER: David John 

PROVIDER: E-MTAB-17783 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress