May 26, 2021
Does stimulation of the soluble guanylate cyclase pathway in late gestation improve intrauterine growth restriction in a reduced uterine perfusion pressure (RUPP) rat model of placental ischemia? In our latest podcast, Stella Goulopoulou (University of North Texas Health Science Center) interviews authors Barbara Alexander and Laura Coats (University of Mississippi Medical Center), along with expert Chris Banek (University of Arizona), about new research by Coats et al. The authors focused specifically on late gestation (day 20 to birth), which provided unique insights when compared to previous work investigating intrauterine growth restriction (IUGR) from gestation day 14 to gestation day 20. After stimulating the soluble guanylate cyclase (sGC) pathway, the authors found neither birth weight nor asymmetrical growth was improved in male offspring. In addition, the IUGR programmed male offspring, who were exposed to stimulation of the sGC pathway during late gestation, continued to develop hypertension at 4 months of age. Many preclinical studies show the benefits of sGC stimulation to the mother early in gestation and assume long-term benefit to the offspring. This work by Coats et al. is both surprising and clinically relevant to the preeclampsia research field, highlighting the crucial need for intervention late in gestation during critical fetal organ development and follow-up after birth. Where does the field go from here? Listen now.
Laura E. Coats, Bhavisha A. Bakrania, Daniel R. Bamrick-Fernandez, Allison M. Ariatti, Adam Z. Rawls, Norma B. Ojeda, Barbara T. Alexander Soluble guanylate cyclase stimulation in late gestation does not mitigate asymmetric intrauterine growth restriction or cardiovascular risk induced by placental ischemia in the rat Am J Physiol Heart Circ Physiol, published May 3, 2021. DOI: 10.1152/ajpheart.00033.2021
May 14, 2021
Can epigenetic analysis of DNA methylation in the myocardial genome be used to evaluate individual differences in response to treatment among heart failure patients? Consulting Editor Dr. Nisha Charkoudian (U.S. Army Research Institute of Environmental Medicine) interviews lead author Dr. Adam Wende (University of Alabama at Birmingham, Birmingham) and expert Dr. Bradford Hill (University of Louisville) about the innovative new study by Pepin et al. The authors studied human heart tissue obtained from heart failure patients during left ventricular assist device (LVAD) placement surgery. Wende and co-authors found that one of the strongest signals in the epigenetic mark DNA methylation was differentially regulated by self-reported race, identifying specific patterns in patients who self-identified as either African American or Caucasian. Long term outcomes were found to be significantly worse in the patient cohort self-identified as African American. Can the epigenetic changes uncovered by the authors help explain why African Americans have a higher susceptibility to heart failure? Listen and find out.
Mark E. Pepin, Chae-Myeong Ha, Luke A. Potter, Sayan Bakshi, Joseph P. Barchue, Ayman Haj Asaad, Steven M. Pogwizd, Salpy V. Pamboukian, Bertha A. Hidalgo, Selwyn M. Vickers, Adam R. Wende Racial and socioeconomic disparity associates with differences in cardiac DNA methylation among men with end-stage heart failure Am J Physiol Heart Circ Physiol, published May 7, 2021. DOI: doi.org/10.1152/ajpheart.00036.2021
May 10, 2021
As we uncover in our latest podcast episode, a meta-analysis of multiple RNA sequencing datasets with different data types leads to truly novel insights. Listen as Consulting Editors Ganesh Halade (University of South Florida) and Taben Hale (University of Arizona) interview authors Adam Engler and Alex Whitehead (University of California, San Diego) about their unique meta-analysis of RNA sequencing data which compared postnatal day 1 and day 8 hearts post-MI. The authors identified two distinct data clusters—an infarct cluster and a sham control cluster—and identified 37 genes which are critically involved in connecting fibroblasts to macrophages in the cardiac remodeling process. Because the authors did not take an either/or approach, and instead focused on both macrophages and fibroblasts, their meta-analysis connected the dots between inflammation and scar formation gene networks. “I think this is a very good example of the sum being greater than the parts,” explained Engler. This innovative work highlights several specific inflammatory processes critical to post-MI remodeling. What cellular and molecular pathways do the authors think should be targeted for therapeutic success? Listen and learn more.
Alexander J. Whitehead and Adam J. Engler Regenerative Crosstalk between Cardiac Cells and Macrophages Am J Physiol Heart Circ Physiol, published March 26, 2021.
May 6, 2021
What do an undergraduate degree in history, the transcription factor Forkhead box class O1 (FoxO1), and maternity leave have in common? In this new episode of our Behind the Bench podcast, host Lisandra de Castro Bras (East Carolina University) and her new co-host Charlotte Usselman (McGill University) interview lead author Kate Weeks (Baker Heart and Diabetes Institute) about a new study by Weeks and co-authors which shows FoxO1 is a critical mediator of exercise-induced cardiac hypertrophy. We reached out to Kate to get the story behind her research, because we know how critically important it is for women scientists to hear from other women scientists about balancing scientific research and life outside the lab. Kate discusses the implications of her study in considering FoxO1 as a target for treating heart disease, and she also discusses the implications of maternity leave on maintaining her career as a research scientist. Interspersed in this engaging and enlightening conversation about Kate’s research are life lessons about planning your career path, taking family leave from work, inquiring about childcare at conferences, and so much more. Listen now.
Kate L. Weeks,Yow Keat Tham, Suzan G. Yildiz, Yonali Alexander, Daniel G. Donner, Helen Kiriazis, Claudia A. Harmawan, Amy Hsu, Bianca C. Bernardo, Aya Matsumoto, Ronald A. DePinho, E. Dale Abel, Elizabeth A. Woodcock, Julie R. McMullen FoxO1 is required for physiological cardiac hypertrophy induced by exercise but not by constitutively active PI3K Am J Physiol Heart Circ Physiol, published April 7, 2021.
DOI: doi.org/ 10.1152/ajpheart.00838.2020