AJP-Heart and Circulatory Physiology Podcast

Guidelines for Mechanistic Modeling and Analysis in Cardiovascular Research

In our latest episode, Dr. Jeff Saucerman (University of Virginia) interviews authors Dr. Naomi Chesler (University of California, Irvine) and Dr. Mitchel Colebank (University of South Carolina) about their new Guidelines in Cardiovascular Research article on incorporating mechanistic modeling into the analysis of experimental and clinical data to identify possible mechanisms of (ab)normal cardiovascular physiology. The authors’ goal is to provide a consensus document that identifies best practices for in silico computational modeling in cardiovascular research. These guidelines provide the necessary methods for mechanistic model development, model analysis, and formal model calibration using fundamentals from statistics. Colebank et al. outline rigorous practices for computational, mechanistic modeling in cardiovascular research and discuss its synergistic value to experimental and clinical data. Would you like to understand how to apply a cone of uncertainty to your experimental data? Listen now to find out more.

 

Mitchel J. Colebank, Pim A. Oomen, Colleen M. Witzenburg, Anna Grosberg, Daniel A. Beard, Dirk Husmeier, Mette S. Olufsen, and Naomi C. Chesler Guidelines for mechanistic modeling and analysis in cardiovascular research Am J Physiol Heart Circ Physiol, published August 6, 2024. DOI: 10.1152/ajpheart.00253.2024

Behind the Bench Episode 15 with Hannah Cizauskas

In this episode of Behind the Bench, we are talking with Hannah Cizauskas about her first, first-author article published in AJP-Heart and Circ. Born and raised in Detroit, Hannah moved to Chicago for what she thought would be just one rotation outside of the cancer genetics field. This led Hannah to work on a project related to atrial fibrillation and contractile dysfunction in Dave Barefield’s lab at Loyola University Chicago’s Cellular and Molecular Physiology Department. Now in the fourth year of her PhD, Hannah is a dog mom to Jake, she loves reading STEMinist novels, and she is researching sarcomere dysfunction in the context of AFib. Listen to this engaging interview with co-hosts Dr. Tommy Martin and Dr. Charlotte Usselman to find out more.

 

Hannah E. Cizauskas, Hope V. Burnham, Azaria Panni, Alexandra Peña, Alejandro Alvarez-Arce, M. Therese Davis, Kelly N. Araujo, Christine E. Delligatti, Eby Edassery, Jonathan A. Kirk, Rishi Arora, and David Y. Barefield Proteolytic degradation of atrial sarcomere proteins underlies contractile defects in atrial fibrillation Am J Physiol Heart Circ Physiol, published August 5, 2024. DOI: 10.1152/ajpheart.00148.2024

Runx1 Drives Cardiomyocyte Cell Cycle Activation

In our latest episode, Executive Editor Kara Hansell Keehan interviews lead author Dr. Michaela Patterson and first author Kaelin Akins (both at the Medical College of Wisconsin) along with expert Dr. Ana Vujic (University of Cambridge) about the new study by Akins et al. Given that the heart has limited regenerative potential, repairing damage to cardiomyocytes after a heart attack is particularly challenging. Cardioregeneration researchers worldwide are searching for potential targets that can stimulate cardiomyocyte proliferation and cardiac regeneration. However, because cardiomyocytes can undergo incomplete cell division, multinucleation, and polyploidization, it is difficult to study true cardiomyocyte proliferation. Akins et al. examined the effect of Runx1 on cardiomyocyte cell cycle during postnatal development and cardiac regeneration using cardiomyocyte-specific gain- and loss-of-function mouse models. Listen now to learn more about how the authors determined that Runx1 is sufficient but not required for cardiomyocyte cell cycle activation.

 

Kaelin A. Akins, Michael A. Flinn, Samantha K. Swift, Smrithi V. Chanjeevaram, Alexandra L. Purdy, Tyler Buddell, Mary E. Kolell, Kaitlyn G. Andresen, Samantha Paddock, Sydney L. Buday, Matthew B. Veldman, Caitlin C. O’Meara, Michaela Patterson Runx1 is sufficient but not required for cardiomyocyte cell-cycle activation Am J Physiol Heart Circ Physiol, published July 21, 2024. DOI: 10.1152/ajpheart.00782.2023

Acute Intranasal Insulin Increases MSNA in Healthy Adults

What is the impact of central insulin on muscle sympathetic nerve activity (MSNA) and vascular conductance in the absence of peripheral insulin delivery? Listen as Associate Editor Dr. Jason Carter (Baylor University) interviews authors Neil McMillan and Dr. Jackie Limberg (both at University of Missouri), along with expert Dr. Manda Keller-Ross (University of Minnesota), about the new Short Report by McMillan et al. To gain a better understanding of the central sympathoexcitatory effects of insulin in humans, the authors recruited two groups of young, healthy individuals. One group served as a time control and the other group received intranasal insulin administration. McMillan et al. measured MSNA from the fibular nerve, combined with continuous monitoring of blood pressure and leg blood flow, before and after insulin administration. Limberg, McMillan and co-authors found that only the individuals who received insulin exhibited an increase in efferent sympathetic nervous system activity, which was coupled with peripheral vasoconstriction and increases in arterial blood pressure. How does this research influence our mechanistic understanding of the sympathetic and hemodynamic response to insulin? Listen now to find out.

 

Neil J. McMillan, Dain W. Jacob, Brian Shariffi, Jennifer L. Harper, Glen E. Foster, Camila Manrique-Acevedo, Jaume Padilla, and Jacqueline K. Limberg Effect of acute intranasal insulin administration on muscle sympathetic nerve activity in healthy young adults Am J Physiol Heart Circ Physiol, published July 3, 2024. DOI: 10.1152/ajpheart.00253.2024

Human Induced Pluripotent Stem Cell Derived Cardiomyocyte Electrophysiology and Experimental Reproducibility

Sometimes experimental results are serendipitous. Listen as Associate Editor Dr. Crystal Ripplinger (University of California, Davis) talks with authors Dr. Nikki Posnack and Devon Guerrelli (both at Children’s National Hospital and The George Washington University School of Engineering and Applied Science), along with expert Dr. Silvia Marchiano (University of Washington), about the new research by Guerrelli et al. published in our Call for Papers on Excitation-Contraction Coupling, Electrophysiology, and Arrhythmias. The Posnack Lab typically investigates environmental chemicals and their impact on cardiac function using microelectrode arrays to record electrical signals from human iPS cells. When performing cardiotoxicity experiments, the authors realized that their baseline measurements varied significantly between their different studies, making it difficult to combine datasets. In doing the legwork to identify potential sources of variability and improve their own internal lab protocols, the authors focused on the reproducibility of their experimental measurements using human iPSCs. Listen as we discuss important recommendations for investigators using these cells to improve their experimental reproducibility.

 

Devon Guerrelli, Jenna Pressman, Shatha Salameh, and Nikki Posnack hiPSC-CM Electrophysiology: Impact of Temporal Changes and Study Parameters on Experimental Reproducibility Am J Physiol Heart Circ Physiol, published June 9, 2024. DOI: 10.1152/ajpheart.00631.2023

Serum Estradiol and Cardiovascular Health Among Transgender and Nonbinary Adults Using Gender Affirming Estrogen Therapy

Hormone modulation therapy is a growing area of research in cardiovascular science related to a number of factors, such as menopause and andropause, cancers in hormone-producing organs, as well as gender-affirming hormone therapy. So how do scientists and clinicians measure, monitor, and balance applications of hormone therapy? In our latest podcast, Associate Dr. Keith Brunt interviews authors Dr. Chantal Rytz (University of Calgary) and Dr. Sofia Ahmed (University of Alberta), along with expert Dr. Nina Stachenfeld (John B. Pierce Laboratory/Yale School of Medicine) about the recent article by Rytz et al. The authors review the use of estrogen in adult transgender, non-binary and gender diverse individuals who are medically managed with hormone modulation therapy for gender affirmation. Their findings indicate that the rate at which serum estrogen concentrations change may be important in order to optimize cardiovascular health and manage risk factors for obesity, hyperlipidemia, and elevated blood pressure. How should scientists account for and explore the hormone state of individuals within a cardiovascular context to improve the foundation of evidence for hormone modulation therapies for clinicians? Listen and learn more.

 

Chantal L. Rytz, Keila Turino Miranda, Paul E. Ronksley, Nathalie Saad, Satish R. Raj, Ranjani Somayaji, Sandra M. Dumanski, Heather Ganshorn, Dina N. Greene, David Collister, Amelia M. Newbert, Lindsay Peace, Sofia B. Ahmed Association between Serum Estradiol and Cardiovascular Health among Transgender Adults Using Gender-Affirming Estrogen Therapy Am J Physiol Heart Circ Physiol, published July 15, 2024. DOI: 10.1152/ajpheart.00151.2024

IL-33 Supplementation Improves RUPP Pathophysiology

While decreased IL-33 signaling has been associated with preeclampsia, the mechanisms linking this signaling pathway to disease pathophysiology are not well understood. In this episode, Associate Editor Dr. Amanda LeBlanc (University of Louisville) interviews author Dr. Denise Cornelius (University of Mississippi Medical Center) and expert Dr. Stella Goulopoulou (Loma Linda University) about the new research study by Wang et al. Using the Reduced Uterine Perfusion Pressure (RUPP) rat model, the authors found evidence that mechanistically links reduced IL-33 with the inflammatory response and vascular dysfunction present in preeclampsia. Is the IL-33 signaling pathway a possible clinical therapeutic target for the treatment of preeclampsia? Listen now to learn more.

 

Xi Wang, Corbin Shields, Geilda Tardo, Greg Peacock, Emily Hester, Marissa Anderson, Jan M. Williams, Denise C. Cornelius IL-33 supplementation improves uterine artery resistance and maternal hypertension in response to placental ischemia Am J Physiol Heart Circ Physiol, published April 3, 2024. DOI: 10.1152/ajpheart.00045.2024

Mitochondrial Isolation in Aged Hearts

In this episode, Associate Editor Dr. Jonathan Kirk (Loyola University Chicago) interviews author Dr. Ed Lesnefsky (Richmond Department of Veterans Affairs Medical Center and Virginia Commonwealth University) and expert Dr. Chi Fung Lee (Oklahoma Medical Research Foundation) about the new Methods and Resources article by Chen et al. published in our Call for Papers on Impact of Aging on the Cardiovascular System. Lesnefsky and coauthors advanced a technique of isolating mitochondria with an emphasis on integrity of the mitochondrial organelles, their function, purity and characterization in order to develop benchmarks in the field for quality control to support collaboration across laboratories. In their research, the authors focus on mitochondrial-driven age-enhanced disease and on mitochondrial defects due to aging, which potentially increase the susceptibility of elderly patients’ hearts to cardiovascular disease. Well-known techniques exist for isolating specific mitochondria populations in mouse hearts. However, Lesnefsky and collaborators found that this resulted in not enough sample to properly interrogate. Therefore Lesnefsky and coauthors investigated whether they could isolate one combined mixed population of mitochondria with a “wild type” physiological model of aging, and whether or not that would that reflect the phenotype. Listen as we discuss the importance of studying mitochondria in an aging model as well as the strategy Lesnefsky and colleagues used to develop their protocol for isolating a mixed mitochondria population. Don’t miss the last few minutes of this conversation for pro tips about the value of networking and career-long mentors. Listen now.

 

Qun Chen, Jeremy Thompson, Ying Hu, and Edward J. Lesnefsky Aging-induced mitochondrial dysfunction: two distinct populations of mitochondria versus a combined population Am J Physiol Heart Circ Physiol, published January 12, 2024. DOI: 10.1152/ajpheart.00363.2023

Guidelines on Use of Sex and Gender in Cardiovascular Research

In our latest episode, Consulting Editor Dr. Kristine DeLeon-Pennell (Medical University of South Carolina) interviews fellow co-authors Dr. Charlotte Usselman (McGill University), Dr. Judy Regensteiner (University of Colorado Anschutz Medical Campus), Dr. Kerrie Moreau (University of Colorado Anschutz Medical Campus), Dr. Austin Robinson (Indiana University Bloomington), Dr. Jesse Moreira-Bouchard (Boston University), and Dr. Quin Denfeld (Oregon Health and Science University) about their recently published guidelines on the use of sex and gender in cardiovascular research. Until recently, the effects of sex and gender in cardiovascular research have been largely ignored in research design and reporting. The result is that women and gender diverse individuals have been understudied in basic and clinical research, leading to a lack of understanding of sex and gender in cardiovascular health and disease. The goal of these guidelines is to provide researchers with practical and actionable advice on best practices to include sex and gender considerations in study design, data collection, analysis, and interpretation. As Dr. Judy Regensteiner points out, “We have to make it doable. We can’t just say, ‘Go do this.’ We have to show people how to do it.” Ready to get started? Listen now to learn more.

 

Charlotte W. Usselman, Merry L. Lindsey, Austin T. Robinson, Beth A. Habecker, Chloe E. Taylor, W. David Merryman, Derek Kimmerly, Jeffrey R. Bender, Judith G. Regensteiner, Kerrie L. Moreau, Louise Pilote, Megan M. Wenner, Myles O’Brien, Timur O. Yarovinsky, Nina S. Stachenfeld, Nisha Charkoudian, Quin E. Denfeld, Jesse D. Moreira-Bouchard, W. Glen Pyle, and Kristine Y. DeLeon-Pennell Guidelines on the use of sex and gender in cardiovascular research Am J Physiol Heart Circ Physiol, published December 21, 2023. DOI: 10.1152/ajpheart.00535.2023

Behind the Bench Episode 14

After a yearlong hiatus, Behind the Bench is back, listeners! In this episode, we welcome back our B2B co-hosts Dr. Charlotte Usselman and Dr. Tommy Martin, who get the story behind the story from the one and only Dr. DeWayne Townsend, corresponding author of the recently published study by Stevens et al. Trust me, you are going to love listening to DeWayne talk about science! As DeWayne rightly points out, if we want to understand a disease before it's a disease, we have to model it in order to figure it out. From the “dastardly Krebs cycle” to grinding up hearts and shouting “fire in the hole!” before using the mouse heart pulverizer (it’s a thing), Dewayne brings to this conversation his best science sound effects, wise insights, and a friendly PSA to contact your Congressional representatives and advocate for science funding. We discuss the resiliency of physiology and the redundancies in the heart that enable scientists to knockout things thought to be important, and as DeWayne points out, the body can still handle it. We cover DeWayne’s interesting path from vet school to cardiovascular physiology, and his best advice to trainees. How do you deal with being wrong most of the time? According to DeWayne, when another beautiful hypothesis is slain by data, push on! It is a slog. Keep going and try to find a way to move the needle. While you’re at it, DeWayne suggests that you learn how to fix your own equipment, try not to drink too much caffeine, and be inspired by other scientists, especially when that scientist is your Dad.

 

Jackie A. Stevens, Tyler C. Dobratz, Kaleb D. Fischer, Alexandria Palmer, Kira Bourdage, Anne J. Wong, Hector Chapoy-Villanueva, Daniel J. Garry, Julia C. Liu, Matthew W. Kay, Sarah Kuzmiak-Glancy, and DeWayne Townsend Mechanisms of reduced myocardial energetics of the dystrophic heart Am J Physiol Heart Circ Physiol, published January 22, 2024. DOI: 10.1152/ajpheart.00636.2023