Cardiac assessment in pediatric mice: strain analysis as a diagnostic measurement.

Echocardiography is a robust tool for assessing cardiac function in both humans and laboratory animals. Conventional echocardiographic measurements, including chamber dimensions, wall thickness, and ejection fraction are routinely obtained to assess cardiac function in mice. Recently, myocardial strain and strain rate measurements have been added to functional assessments to provide additional details on regional abnormalities that are not evident using conventional measurements. To date, all studies of strain and strain rate in mice or rats have involved adult animals. This study serves to outline methods for acquiring echocardiographic images in pediatric mice and to provide myocardial strain and strain rate values for healthy C57BL/6J mice between 3 and 11 weeks old. Between weeks 3 and 11, left ventricular radial strain ranged from 32 to 43% and longitudinal strain ranged from -15 to -19%, with analysis over time showing no significant changes with aging (radial strain, P = 0.192 and longitudinal strain, P = 0.264; n = 4 for each time point evaluated). In conclusion, myocardial strain analysis in pediatric mice is technically feasible and has potential application in studying the pathophysiology of pediatric cardiovascular disease.

Negative elongation factor controls energy homeostasis in cardiomyocytes.

Negative elongation factor (NELF) is known to enforce promoter-proximal pausing of RNA polymerase II (Pol II), a pervasive phenomenon observed across multicellular genomes. However, the physiological impact of NELF on tissue homeostasis remains unclear. Here, we show that whole-body conditional deletion of the B subunit of NELF (NELF-B) in adult mice results in cardiomyopathy and impaired response to cardiac stress. Tissue-specific knockout of NELF-B confirms its cell-autonomous function in cardiomyocytes. NELF directly supports transcription of those genes encoding rate-limiting enzymes in fatty acid oxidation (FAO) and the tricarboxylic acid (TCA) cycle. NELF also shares extensively transcriptional target genes with peroxisome proliferator-activated receptor α (PPARα), a master regulator of energy metabolism in the myocardium. Mechanistically, NELF helps stabilize the transcription initiation complex at the metabolism-related genes. Our findings strongly indicate that NELF is part of the PPARα-mediated transcription regulatory network that maintains metabolic homeostasis in cardiomyocytes.

Using proteomics to uncover extracellular matrix interactions during cardiac remodeling.

The left ventricle (LV) responds to a myocardial infarction with an orchestrated sequence of events that result in fundamental changes to both the structure and function of the myocardium. This collection of responses is termed as LV remodeling. Myocardial ischemia resulting in necrosis is the initiating event that culminates in the formation of an extracellular matrix (ECM) rich infarct scar that replaces necrotic myocytes. While the cardiomyocyte is the major cell type that responds to ischemia, infiltrating leukocytes and cardiac fibroblasts coordinate the subsequent wound healing response. The matrix metalloproteinase family of enzymes regulates the inflammatory and ECM responses that modulate scar formation. Matridomics is the proteomic evaluation focused on ECM, while degradomics is the proteomic evaluation of proteases as well as their inhibitors and substrates. This review will summarize the use of proteomics to better understand matrix metalloproteinase roles in post myocardial infarction LV remodeling.