Selected Grantee Publications
Profiling Development of Abdominal Organs in the Pig
Gabriel et al., Scientific Reports. 2022.
https://www.doi.org/10.1038/s41598-022-19960-5
The pig is a model system for studying human development and disease due to its similarities to human anatomy, physiology, size, and genome. Moreover, advances in CRISPR gene editing have made genetically engineered pigs a viable model for the study of human pathologies and congenital anomalies. However, a detailed atlas illustrating pig development is necessary for identifying and modeling developmental defects. Here, the authors describe normal development of the pig abdominal system (i.e., kidney, liver, pancreas, spleen, adrenal glands, bowel, gonads) and compare them with congenital defects that can arise in gene-edited SAP130 mutant pigs. This atlas and the methods described here can be used as tools for identifying developmental pathologies of the abdominal organs in the pig at different stages of development. Supported by ORIP (U42OD011140), NHLBI, NIAID, NIBIB, NICHD, and NINDS.
Mineralocorticoid Receptor Blockade Normalizes Coronary Resistance in Obese Swine Independent of Functional Alterations in Kv Channels
Goodwill et al., Basic Research in Cardiology. 2021.
https://pubmed.ncbi.nlm.nih.gov/34018061/
Impaired coronary microvascular function (e.g., reduced dilation and coronary flow reserve) predicts cardiac mortality in obesity. Mineralocorticoid receptor (MR) antagonism improves coronary microvascular function in obese humans and animals. Inhibition of Kv channels reduced coronary blood flow and augmented coronary resistance under baseline conditions in lean but not obese swine and had no impact on hypoxemic coronary vasodilation. MR blockade prevented obesity-associated coronary arteriolar stiffening independent of cardiac capillary density and changes in cardiac function. These data indicate that chronic MR inhibition prevents increased coronary resistance in obesity independent of Kv channel function and is associated with mitigation of obesity-mediated coronary arteriolar stiffening. Supported by ORIP (U42OD011140, S10OD023438), NHLBI, and NIBIB.