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Animal Models

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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.

Establishing an Immunocompromised Porcine Model of Human Cancer for Novel Therapy Development with Pancreatic Adenocarcinoma and Irreversible Electroporation

Hendricks-Wenger et al., Scientific Reports. 2021.

https://pubmed.ncbi.nlm.nih.gov/33828203/

Efficacious interventions to treat pancreatic cancer lack a preclinical model to recapitulate patients' anatomy and physiology. The authors developed RAG2/IL2RG deficient pigs using CRISPR/Cas9 with the novel application of cancer xenograft studies of human pancreatic adenocarcinoma. These pigs were successfully generated using on-demand genetic modifications in embryos. Human Panc01 cells injected into the ears of RAG2/IL2RG deficient pigs demonstrated 100% engraftment. The electrical properties and response to irreversible electroporation of the tumor tissue were found to be similar to excised human pancreatic cancer tumors. This model will be useful to bridge the gap of translating therapies from the bench to clinical application. Supported by ORIP (R21OD027062), NIBIB, and NCI.