AJP-Heart and Circulatory Physiology Podcast

Sleep Deprivation and Endothelial Function

Sleep disorders, such as insomnia, sleep apnea and restless leg syndrome, have acute and chronic negative cardiovascular impacts. Why is so little known about the cellular and molecular mechanisms regulating cardiovascular events in sleep disorders? In this podcast Editor-in-Chief Dr. Irving H. Zucker interviews lead author Dr. Maureen MacDonald (McMaster University) and expert Karyn Esser (University of Florida) about an insightful new Review article by Cherubini et al. MacDonald and co-authors became interested in the affect sleep has on endothelial function while conducting their own exercise physiology studies. Reviewing the literature, Cherubini et al. found that most studies do not control for sleep, yet sleep deprivation – whether acute or chronic, partial or total – can have negative effects on endothelial function in humans. The literature also shows similar results in animal and cell culture models. Because clock mechanisms exist in every human cell type, the understanding of links between so-called “clock genes” and disease progression is an emerging field. How does this relate to the development of atherosclerotic plaques, and the potential for exercise as a therapeutic strategy to combat the negative impact of disordered sleep? Listen now.

 

Joshua M. Cherubini, Jem L. Cheng, Jennifer S Williams, Maureen J. MacDonald Sleep deprivation and endothelial function: reconciling seminal evidence with recent perspectives  Am J Physiol Heart Circ Physiol, published October 16, 2020. DOI: doi.org/10.1152/ajpheart.00607.2020

Behind the Bench Episode7

Why should medical school students invest their time in basic science research? That’s our theme for this episode of Behind the Bench from AJP-Heart and Circ. Hosts Lisandra de Castro Brás (East Carolina University) and Jonathan Kirk (Loyola University Chicago) interview Dhandevi Persand and Nicole Maddie, both students at the New York Institute of Technology College of Osteopathic Medicine. Dhandevi and Nicole won the FASEB Dream Award to attend the APS Professional Skills Training Course on Writing and Reviewing for Scientific Journals, and they have co-authored a New Investigator Editorial detailing their experiences. More importantly, Dhandevi and Nicole are using their platform as Women in Stem to promote the importance of research for clinical trainees. As students in the NYIT Doctor of Osteopathic Medicine (D.O.) program, Nicole and Dhandevi focus on how structure affects function. The translational research projects they have both worked on have cemented their feelings that research is critically important for medical students and clinicians. Did you know that D.O. students must complete 200 additional hours of coursework, compared to M.D. students, in order to learn osteopathic manipulative medicine? Listen for a refreshingly open conversation about time management and reaching for “stretch goals” which turn out to be surprisingly attainable.

 

Dhandevi Persand and Nicole Maddie New investigator editorial: the osteopathic medical student perspective on research Am J Physiol Heart Circ Physiol, published December 2, 2020. DOI: doi.org/10.1152/ajpheart.00813.2020

Role of Estrogen Receptor Alpha in Right Ventricular Remodeling

Does the loss of functional estrogen receptor alpha (ERα) remove female protection from adverse remodeling? We know that right ventricular function is preserved in women with pulmonary arterial hypertension compared to men. While ERα has been identified as a likely mediator of cardioprotection in the right ventricle, the exact role of ERα in preserving right ventricular function and remodeling in pressure overload is not well understood. In this episode Guest Editor Kristine DeLeon-Pennell (Medical University of South Carolina) interviews lead author Naomi Chesler (University of California Irvine) and expert Jessica Faulkner (Augusta University) about a new study by Cheng et al that utilized a sex-independent pulmonary arterial banding model in both female and male ERα mutant rats to investigate sex-dependent differences in right ventricular response to pressure overload. In females, ERα is protective against right ventricular pulmonary vascular uncoupling, diastolic dysfunction, and fibrosis in response to pressure overload. However, the authors did not observe the same effects in males. Given that only the ERα mutant females showed a dramatic fibrotic response, were the authors surprised by what their RNA sequencing analysis revealed? Listen and find out.

 

Tik-Chee Cheng, Jennifer L Philip, Diana Marcela Tabima, Santosh Kumari, Bakhtiyor Yakubov, Andrea L Frump, Timothy A. Hacker, Alessandro Bellofiore, Rongbo Li, Xin Sun, Kara N. Goss, Tim Lahm, Naomi Chesler Estrogen Receptor Alpha Prevents Right Ventricular Diastolic Dysfunction and Fibrosis in Female Rats  Am J Physiol Heart Circ Physiol, published October 16, 2020. DOI: doi.org/10.1152/ ajpheart.00247.2020

Formaldehyde Exposure Decreases Vascular Function

What are the short-term vascular consequences of formaldehyde exposure in healthy female adults? In our latest podcast episode, Guest Editor Matthew Gorr (The Ohio State University) interviews lead author Stephen Ratchford (Appalachian State University) and expert Thiago Bruder (University of Pittsburgh) about the recent work by Augenreich et al, which was published as part of the AJP-Heart and Circulatory Physiology Call for Papers on Environmental Inhalants and Cardiovascular Disease. Utilizing a natural exposure model that measured via ultrasound the vascular response of students exposed to formaldehyde during their cadaver dissection laboratory coursework, Ratchford and co-authors found significantly decreased flow mediated dilation in the brachial artery, yet no changes in microvascular function. Ratchford and colleagues determined that only one short-term exposure to formaldehyde can have detrimental effects on vascular health. What is the significance of these finding for people exposed to formaldehyde for longer periods of time, such as instructors in cadaver dissection courses? Formaldehyde is a common preservative used in many industries, such as the cosmetic, lumber and construction industries. What are the implications related to occupational and environmental safety standards? Listen now.

 

Marc Andrew Augenreich, Jonathon Lee Stickford, Nina Stute, Laurel Kaitlyn Koontz, Janet M. Cope, Cynthia Bennett, Stephen M. Ratchford Vascular Dysfunction and Oxidative Stress Caused by Acute Formaldehyde Exposure in Female Adults  Am J Physiol Heart Circ Physiol, published October 16, 2020. DOI: doi.org/10.1152/ ajpheart.00605.2020

Post-infarction Cardiac Rupture

Why is it important to have clear diagnostic criteria to use when assessing cardiac rupture in the mouse model of permanent occlusion myocardial infarction? Listen as Deputy Editor Merry L. Lindsey (University of Nebraska Medical Center) interviews lead author Nikolaos Frangogiannis (Albert Einstein College of Medicine) and expert Kristine DeLeon-Pennell (Medical University of South Carolina) about the new study by Hanna et al which compared results from their in-depth histopathological examination with visual inspection of cardiac rupture. Frangogiannis and co-authors found that identifying the rupture site had high specificity but low sensitivity, with a low rate of false positives. Conversely, identifying hemothorax had high sensitivity yet low specificity. Hanna et al. observed key sex differences in their non-reperfusion mouse model of MI. In addition, differences in macrophages and fibroblasts in mice of both sexes which died of cardiac rupture indicated that a perturbed balance of inflammatory mediators may be a factor in the pathogenesis of cardiac rupture. What is the key take-away? When evaluating the cause of death in infarcted mice, look for the rupture site. Listen now.

 

Anis Hanna, Arti V Shinde, and Nikolaos G. Frangogiannis Validation of diagnostic criteria and histopathological characterization of cardiac rupture in the mouse model of non-reperfused myocardial infarction Am J Physiol Heart Circ Physiol, published October 15, 2020. DOI: doi.org/10.1152/ ajpheart.00318.2020

DCM Mutations Alter Intracellular Ca2+ and Signaling

What can three mutations in thin filament regulatory proteins associated with dilated cardiomyopathy tell us about the highly variable phenotypes of DCM? Listen as Associate Editor Crystal Ripplinger (University of California Davis) interviews lead author Paul Robinson (University of Oxford) and expert Michael Greenberg (Washington University in St. Louis) about the latest work by Robinson and co-authors. By studying functional changes in cardiomyocyte contraction, calcium handling and signaling, Robinson and co-authors hoped to identify common pathway activations in troponin T, troponin I and tropomyosin mutations. Why did the authors opt to study DCM mutations in guinea pig cardiomyocytes rather than in a mouse model? Given the substantial number of mutations in both pediatric and adult-onset DCM, what are the implications here for precision medicine in the treatment of this disease? Listen to learn more.

 

Paul Robinson, Alexander J. Sparrow, Suketu Patel, Marta Malinowska, Svetlana N. Reilly, Yin-Hua Zhang, Barbara Casadei, Hugh Watkins, Charles Redwood Dilated cardiomyopathy mutations in thin-filament regulatory proteins reduce contractility, suppress systolic Ca2+, and activate NFAT and Akt signaling Am J Physiol Heart Circ Physiol, published July 21, 2020. DOI: doi.org/10.1152/ajpheart.00272.2020

Endothelial ERBB4 and Cardiac Remodeling

Does neuregulin-1 autocrine signaling by endothelial cells regulate left ventricular remodeling? Listen as Deputy Editor Merry Lindsey (University of Nebraska Medical Center) interviews lead authors Gilles De Keulenaer and Vincent Segers (both at University of Antwerp), along with expert Ganesh Halade (University of South Florida), about the novel work by Dugaucquier et al. The authors investigated responses to pressure overload using transverse aortic constriction, angiontensin II infusion, and myocardial infarction, in an endothelial cell-specific ERBB4 knockout mouse model. Surprising results serve to highlight the spatial and temporal heterogeneity of left ventricular autocrine and paracrine responses to cardiac injury. What’s more, these results lead the authors to believe that paracrine and autocrine signaling are integrally connected and equally influential on cardiac remodeling. “By performing this study, we now look at autocrine signaling in the myocardium in a completely different fashion,” explained De Keulenaer. Why? Listen now.

 

Lindsey Dugaucquier, Eline Feyen, Ligia Mateiu, Tine Anne Marie Bruyns, Gilles W. De Keulenaer, Vincent F. M. Segers The role of endothelial autocrine NRG1/ERBB4 signaling in cardiac remodeling Am J Physiol Heart Circ Physiol, published August 4, 2020. DOI: doi.org/10.1152/ajpheart.00176.2020

Behind the Bench Episode 6 with Aurore Lyon

Everyone has a story, and no one is ordinary. That’s our theme for this episode of Behind the Bench from AJP-Heart and Circ. Hosts Lisandra de Castro Bras (East Carolina University) and Jonathan Kirk (Loyola University Chicago) talk with Aurore Lyon (Maastricht University), the first author of “Differentiating the effects of beta-adrenergic stimulation and stretch on calcium and force dynamics using a novel electromechanical cardiomyocyte model,” published in August 2020. Aurore pursued a master’s degree, followed by a PhD, at Oxford University. She is now completing a post-doctoral fellowship in the Department of Biomedical Engineering within the Cardiovascular Research Institute Maastricht at Maastricht University. Aurore’s story is about finding a passion in an unexpected field while pursuing research in a completely different area. From engineering to cardiovascular research, Aurore brings a refreshing perspective to navigating career and life across countries and cultures. Ready to change directions in your own career? Listen for inspiration.

 

Aurore Lyon, Lauren J. Dupuis, Theo Arts, Harry J. G. M. Crijns, Frits W. Prinzen, Tammo Delhaas, Jordi Heijman, Joost Lumens Differentiating the effects of β-adrenergic stimulation and stretch on calcium and force dynamics using a novel electromechanical cardiomyocyte model Am J Physiol Heart Circ Physiol, published August 19, 2020. DOI: doi.org/10.1152/ajpheart.00275.2020

Vascular Response to Prolonged Sitting in Hypercapnia

What are the potential detrimental interactions between prolonged sitting and mild hypercapnia on autonomic system activity, vascular function, and microvascular oxygenation? In this episode, Editor-in-Chief Irv Zucker (University of Nebraska Medical Center) interviews lead author Song-Young Park (University of Nebraska at Omaha) and expert Camilla Wenceslau (University of Toledo) about the latest study by Headid et al., which found that prolonged sitting attenuated systemic and peripheral vascular endothelial function, as well as microvascular function in healthy adults. Park and co-authors also found that prolonged sitting coupled with mild hypercapnic conditions that mimic everyday environments in workplaces, office buildings, and school classrooms resulted in exacerbated peripheral vascular and microvascular dysfunction. Listen as we discuss how prolonged sitting may aggravate disease conditions such as sleep apnea, COPD, and obesity. What are the potential implications of this research for students spending long hours sitting indoors with restricted movement due to COVID-19 pandemic restrictions? Listen to find out.

 

Ronald J. Headid 3rd, Elizabeth J. Pekas, TeSean K. Wooden, Won-Mok Son, Gwenael Layec, John Shin, Song-Young Park Impacts of prolonged sitting with mild hypercapnia on vascular and autonomic function in healthy recreationally active adults Am J Physiol Heart Circ Physiol, published August 4, 2020. DOI: doi.org/10.1152/ajpheart.00354.2020

[U-13C]-glucose and In Vivo Heart Metabolism

What is the “metabolic fate” of glucose in mice with pressure-overload or volume-overload induced cardiac hypertrophy? Listen as Associate Editor Fabio Recchia (Temple University and Scuola Superiore Sant'Anna) interviews lead author, and fellow Associate Editor, Ajay Shah (King’s College London) along with experts Christoph Maack and Edoardo Bertero (both at University Clinic Würzburg) about the new study by Schnelle et al. “Metabolism is integrally linked to structural and functional changes that occur in the remodeling heart.” By implementing a method of heavy carbon labeling in vivo, and utilizing nuclear magnetic resonance spectroscopy, Schnelle et al. found notable differences in the pressure-overload mouse model of transverse aortic constriction (TAC) but not in the volume-overload TAC model. What is the significance of an increase in flux in the tricarboxylic acid cycle (TCA) during pressure-overload? How did the authors interpret the evidence of increased glutamine and aspartate, neither of which are TCA metabolites? Listen to find out.

 

Moritz Schnelle, Mei Chong, Anna Zoccarato, Manar Elkenani, Greta Jane Sawyer, Gerd Hasenfuss, Christian Ludwig, Ajay M. Shah In vivo [U-13C]glucose labeling to assess heart metabolism in murine models of pressure and volume overload Am J Physiol Heart Circ Physiol, published August 4, 2020. DOI: doi.org/10.1152/ajpheart.00219.2020