Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1.
Yidong WangBingruo WuPengfei LuDonghong ZhangBrian WuShweta VarshneyGonzalo Del Monte-NietoZhenwu ZhuangRabab CharafeddineAdam H KramerNicholas E S SibingaNikolaos G FrangogiannisRichard N KitsisRalf H AdamsKari AlitaloDavid J SharpRichard P HarveyPamela StanleyBin ZhouPublished in: Nature communications (2017)
Coronary artery anomalies may cause life-threatening cardiac complications; however, developmental mechanisms underpinning coronary artery formation remain ill-defined. Here we identify an angiogenic cell population for coronary artery formation in mice. Regulated by a DLL4/NOTCH1/VEGFA/VEGFR2 signaling axis, these angiogenic cells generate mature coronary arteries. The NOTCH modulator POFUT1 critically regulates this signaling axis. POFUT1 inactivation disrupts signaling events and results in excessive angiogenic cell proliferation and plexus formation, leading to anomalous coronary arteries, myocardial infarction and heart failure. Simultaneous VEGFR2 inactivation fully rescues these defects. These findings show that dysregulated angiogenic precursors link coronary anomalies to ischemic heart disease.Though coronary arteries are crucial for heart function, the mechanisms guiding their formation are largely unknown. Here, Wang et al. identify a unique, endocardially-derived angiogenic precursor cell population for coronary artery formation in mice and show that a DLL4/NOTCH1/VEGFA/VEGFR2 signaling axis is key for coronary artery development.
Keyphrases
- coronary artery
- pulmonary artery
- cell proliferation
- heart failure
- high fat diet induced
- left ventricular
- single cell
- vascular endothelial growth factor
- blood flow
- atrial fibrillation
- insulin resistance
- metabolic syndrome
- adipose tissue
- bone marrow
- weight gain
- cell death
- cell cycle arrest
- cardiac resynchronization therapy