Heart regeneration requires multiple cell types to enable cardiomyocyte (CM) proliferation. How these cells interact to create growth niches is unclear. Here, we profile proliferation kinetics of cardiac endothelial cells (CECs) and CMs in the neonatal mouse heart and find that they are spatiotemporally coupled. We show that coupled myovascular expansion during cardiac growth or regeneration is dependent upon VEGF-VEGFR2 signaling, as genetic deletion of Vegfr2 from CECs or inhibition of VEGFA abrogates both CEC and CM proliferation. Repair of cryoinjury displays poor spatial coupling of CEC and CM proliferation. Boosting CEC density after cryoinjury with virus encoding Vegfa enhances regeneration. Using Mendelian randomization, we demonstrate that circulating VEGFA levels are positively linked with human myocardial mass, suggesting that Vegfa can stimulate human cardiac growth. Our work demonstrates the importance of coupled CEC and CM expansion and reveals a myovascular niche that may be therapeutically targeted for heart regeneration.

Background: Heart regeneration requires multiple cell types to enable cardiomyocyte (CM) proliferation. How these cells interact to create growth niches is unclear. Here we profile proliferation kinetics of cardiac endothelial cells (CECs) and CMs in the neonatal mouse heart and find that they are spatiotemporally coupled. Methods and Results: We show that coupled myovascular expansion during cardiac growth or regeneration is dependent upon VEGF-VEGFR2 signaling, as genetic deletion of Vegfr2 from CECs or inhibition of VEGFA abrogates both CEC and CM proliferation. Repair of cryoinjury displays poor spatial coupling of CEC and CM proliferation. Boosting CEC density after cryoinjury with virus encoding Vegfa enhances regeneration. Using Mendelian randomization, we demonstrate that circulating VEGFA levels are positively linked with human myocardial mass, suggesting that Vegfa can stimulate human cardiac growth. Conclusions: Our work demonstrates the importance of coupled CEC and CM expansion and reveals a myovascular niche that may be therapeutically targeted for heart regeneration.

Abdominal pain is a common presentation in the emergency department (ED). Ultrasound is the first-line diagnostic imaging modality for right upper quadrant pain. Point-of-care ultrasound (POCUS) is a focused examination that can be performed at the patient’s bedside to evaluate acute and emergent biliary pathology. The advantages of POCUS include avoiding the potential safety risks associated with transporting critically ill patients, no exposure to ionizing radiation, potentially reduced costs, and rapid diagnosis. This narrative review synthesizes key sonographic findings and techniques for emergent and non-emergent biliary diseases that physicians should recognize at first glance. We present significant and interesting images of cholelithiasis, acute cholecystitis, emphysematous gallbladder, choledocholithiasis or sludge, Mirizzi syndrome, post-operative biliary obstruction, gallbladder polyps, biliary neoplasms, and malignant-appearing lesions or masses. Finally, this review integrates POCUS into clinical pathways to guide decisions regarding additional abdominal imaging, such as computed tomography or radiology-performed ultrasound, and surgical consultation.