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However, how microRNAs influence cardiac endothelial cells in CHD remains unclear. This study identified elevated microRNA-187 (miR-187) expression in embryonic heart endothelial cells from CHD fetuses. Using a conditional knockin model, we showed that increased miR-187 levels in embryonic endothelial cells induce CHD in homozygous fetal mice, closely mirroring human CHD. Mechanistically, miR-187 targets\n                    <jats:italic>NIPBL<\/jats:italic>\n                    , which is responsible for recruiting the cohesin complex and facilitating chromatin accessibility. Consequently, the endothelial cell\u2013specific upregulation of miR-187 inhibited NIPBL, leading to reduced chromatin accessibility and impaired gene expression, which hindered endothelial cell development and ultimately caused heart septal defects and reduced heart size both in vitro and in vivo. Importantly, exogenous miR-187 expression in human cardiac organoids mimicked developmental defects in the cardiac endothelial cells, and this was reversible by NIPBL replenishment. Our findings establish the miR-187\/NIPBL axis as a potent regulator that inhibits cardiac endothelial cell development by attenuating the transcription of numerous endothelial genes, with our mouse and human cardiac organoid models effectively replicating severe defects from minor perturbations. This discovery suggests that targeting the miR-187\/NIPBL pathway could offer a promising therapeutic approach for CHD.\n                  <\/jats:p>","DOI":"10.1172\/jci178355","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T12:43:02Z","timestamp":1732538582000},"source":"Crossref","is-referenced-by-count":11,"title":["Elevated microRNA-187 causes cardiac endothelial dysplasia to promote congenital heart disease through inhibition of NIPBL"],"prefix":"10.1172","volume":"135","author":[{"given":"Chao","family":"Li","sequence":"first","affiliation":[{"name":"Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, Children\u2019s Hospital, and"},{"name":"Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, 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