AJP-Heart and Circulatory Physiology Podcast

Cortical Bone Stem Cells Effects on Cardiac Wound Healing

What’s better than discussing one paper on the effects of cortical bone stem cells and their impact on myocardial infarction? Discussing two papers! Associate Editor Dr. Jonathan Kirk (Loyola University Chicago Stritch School of Medicine) interviews lead authors Dr. Timothy McKinsey (University of Colorado Anschutz Medical Campus) and Dr. Steven R. Houser (Lewis Katz School of Medicine at Temple University) along with expert Dr. Helen Collins (University of Louisville School of Medicine). The latest collaborations from the Houser lab and the McKinsey lab could pave the way for significant advancements in understanding how exosomes derived from cortical bone stem cells (CBSCs) may have the ability to reduce injury from acute myocardial infarction (MI). In the study by Schena et al., Houser and co-authors used an ischemia/reperfusion model and found that, if given soon enough after injury, CBSC-derived exosomes had an acute protective effect on infarct size. The authors then found that secreted factors from CBSCs and their exosomes modified fibroblasts in ways that likely alter MI scar formation. In the study by Hobby et al., McKinsey and co-authors found that CBSCs influence macrophage polarity in vitro toward an anti-inflammatory protective phenotype. Those macrophages, which had been treated with CBSC-derived factors, influenced fibroblasts to become less fibrotic yet more proliferative. Enter small nucleolar RNA (snoRNA) into this story as important regulators of protein translation. Downregulating snoRNAs in turn downregulated protein translation and blocked fibroblast activation. Our experts discuss the advantages and challenges of conducting large animal studies, the opportunities for discovery with snoRNAs, and the exciting future ahead for translational heart failure research. Listen and learn more.

 

Giana J. Schena, Emma K. Murray, Alycia N. Hildebrand, Alaina L. Headrick, Yijun Yang, Keith A. Koch, Hajime Kubo, Deborah Eaton, Jaslyn Johnson, Remus Berretta, Sadia Mohsin, Raj Kishore, Timothy A. McKinsey, John W. Elrod, and Steven R. Houser Cortical bone stem cell-derived exosomes’ therapeutic effect on myocardial ischemia-reperfusion and cardiac remodeling Am J Physiol Heart Circ Physiol, published November 8, 2021. DOI: 10.1152/ajpheart.00197.2021

 

Alexander R. H. Hobby, Remus M. Berretta, Deborah M. Eaton, Hajime Kubo, Eric Feldsott, Yijun Yang, Alaina L. Headrick, Keith A. Koch, Marcello Rubino, Justin Kurian, Mohsin Khan, Yinfei Tan, Sadia Mohsin, Stefania Gallucci, Timothy A. McKinsey, and Steven R. Houser Cortical bone stem cells modify cardiac inflammation after myocardial infarction by inducing a novel macrophage phenotype Am J Physiol Heart Circ Physiol, published September 23, 2021. DOI: 10.1152/ajpheart.00304.2021

New Permeability Assessment of Microvessels-on-a-Chip

Permeability is an important measure of the exchange function of microvessels, but until now, there has been a lack of physiologically-relevant in vitro microvessel models that allow an easy assessment of permeability properties of the microvessel wall. In our latest episode, Associate Editor Amanda LeBlanc (University of Louisville) interviews lead author Ping He (Penn State University) and expert Robert Hester (University of Mississippi Medical Center) about the latest research study by Gao et al., published in the AJP-Heart and Circ Call for Papers on Deconstructing Organs: Single-Cell Analyses, Decellularized Organs, Organoids, and Organ-on-a-Chip Models. Dr. He and colleagues developed a novel microvessel-on-a-chip model which allows endothelial cells to grow under continuous flow, simulating the in vivo environment, while also allowing for the assessment barrier function of the microvessel wall. The in vitro microvessel model Gao et al. developed features layers of glycocalyx and endothelium, and as Dr. He points out, endothelial junctions and glycocalyx are key components contributing to microvessel barrier function and acute inflammatory responses observed in in vivo models. Listen as we discuss the future directions of this model in both acute and chronic conditions, disease states and future molecular studies.

 

Feng Gao, Haoyu Sun, Xiang Li, Pingnian He Leveraging avidin/biotin interaction to quantify permeability of microvessels-on-a-chip  Am J Physiol Heart Circ Physiol, published December 13, 2021.
DOI: 10.1152/ajpheart.00478.2021

Exercise and Cerebrovascular Function

It is well known that exercise can have beneficial effects on brain health, including reducing the risk of dementia and stroke. Does resistance exercise training affect brain blood flow and cerebrovascular physiology differently than endurance exercise? Guest Host Brady Holmer (University of Florida) interviews first author Hannah Thomas (The University of Western Australia) and expert Timo Klein (University of Rostock) about the latest research by Thomas and co-authors which directly compared adaptations in the brain and cerebrovascular function to these two different exercise modalities. Using a randomized cross-over study design to directly compare participant responses to resistance exercise and endurance exercise, young healthy individuals completed 3 months of resistance training 3 times per week, followed by 3 months of endurance training 3 times per week. To develop a comprehensive picture of adaptations occurring in the cerebrovasculature of the study participants, Thomas and collaborators measured middle and posterior cerebral arteries using transcranial Doppler ultrasound to determine blood velocity. In addition, Thomas et al. measured internal carotid and vertebral arteries using duplex ultrasound to assess both diameter and blood flow velocity. What changes in cerebrovascular function did Thomas et al. find in response to resistance training that were not found in response to endurance training? Could these findings lead to possible clinical applications of exercise as preventative therapy for aging, cognitive impairment, and cerebrovascular dysfunction related to dementia? Listen now.

 

Hannah J. Thomas, Channa E. Marsh, Louise H. Naylor, Philip N. Ainslie, Kurt J. Smith, Howard H. Carter, and Daniel J. Green Resistance, but not endurance exercise training, induces changes in cerebrovascular function in healthy young subjects Am J Physiol Heart Circ Physiol, published October 11, 2021. DOI: 10.1152/ajpheart.00230.2021

Sex and Gender Use for AJP-Heart and Circ

What are the goals and expectations of AJP-Heart and Circulatory Physiology over the next several years to optimize rigorous approaches to consideration of sex and gender as a biological variable in cardiovascular research? Consulting Editor Nisha Charkoudian (U.S. Army Research Institute of Environmental Medicine) interviews the entire AJP-Heart and Circ editorial team in this pivotal episode of The AJP-Heart and Circ Podcast. Listen as Editor-in-Chief Merry Lindsey (University of Nebraska Medical Center), Deputy Editor Zamaneh Kassiri (University of Alberta), and Associate Editors Keith Brunt (Dalhousie University), Jason Carter (Montana State University), Jonathan Kirk (Loyola University Chicago), Petra Kleinbongard (University of Duisburg-Essen Medical School), Amanda Jo LeBlanc (University of Louisville), Crystal Ripplinger (University of California-Davis) and Executive Editor Kara Hansell Keehan (American Physiological Society) discuss their recent editorial on expectations for use of sex and gender in cardiovascular research published in AJP-Heart and Circ. The editorial team first assessed reporting of sex and gender in AJP-Heart and Circ articles, and found that, while most studies did report sex/gender, most studies did not use both sexes/genders. By January 2023, AJP-Heart and Circ expects authors to use both sexes/genders in studies submitted to the journal, unless there is strong scientific justification otherwise. What constitutes “strong scientific justification”? Do studies need to be sufficiently powered to detect sex differences? How should authors analyze aggregate data? We tackle these questions in the context of human physiology, small and large animal models, and cell physiology. Why use both sexes/genders? “Put simply, it’s only going to make the research stronger,” stated Jason Carter. This is a must-listen episode!

 

Merry L. Lindsey, Amanda J. LeBlanc, Crystal M. Ripplinger, Jason R. Carter, Jonathan A. Kirk, Kara Hansell Keehan, Keith R. Brunt, Petra Kleinbongard, and Zamaneh Kassiri Reinforcing rigor and reproducibility expectations for use of sex and gender in cardiovascular research   Am J Physiol Heart Circ Physiol, published September 15, 2021. DOI: 10.1152/ajpheart.00418.2021

Experimental Spinal Cord Injury and Orthostatic Hypotension

What is the causal relationship between high-level spinal cord injury, orthostatic hypotension and increased risk for cardiovascular disease? In this episode, Consulting Editor Patrick Osei-Owusu (Case Western Reserve University) interviews authors Christopher West (University of British Columbia) and Aaron Phillips (University of Calgary), along with expert Jill Wecht (James J. Peters VA Medical Center) about the new study by Hayes et al. High-level spinal cord injury can lead to orthostatic hypotension, a debilitating condition experienced by a substantial number of both cervical and high thoracic spinal cord injury (SCI) patients. Yet how this impacts the heart and cerebral vasculature is not well understood in this population. By creating a novel experimental animal model of lower body negative pressure, the authors were able to study how the brain vasculature and heart respond to an orthostatic challenge. Hayes et al. first quantified how much negative pressure was needed to replicate clinically-relevant orthostatic hypotension in rodents with SCI. The authors then introduced the lower body negative pressure technique, and measured cardiac pressure and volume responses in rodents with and without SCI. Finally, the authors imaged the mid-cerebral artery and analyzed step-wise reductions in blood pressure during lower body negative pressure to understand the relationship of pressure to flow in the cerebrovasculature in rodents with and without SCI. What did the authors find and what is the clinical significance of this novel experimental model of lower body negative pressure that allows for real-time micro-analysis in multiple organ systems? Listen to find out.

 

Brian D. Hayes, Mary Pauline Mona Fossey, Malihe-Sadat Poormasjedi-Meibod, Erin Erskine, Jan Elaine Soriano, Berkeley Scott, Ryan Rosentreter, David J. Granville, Aaron A. Phillips, and Christopher R. West Experimental high thoracic spinal cord injury impairs the cardiac and cerebrovascular response to orthostatic challenge in rats Am J Physiol Heart Circ Physiol, published September 23, 2021. DOI: 10.1152/ajpheart.00239.2021

Immune Cell β2-Adrenergic Receptor in the Heart

How do β-adrenergic receptor subtypes regulate immune function in the heart? In this unique episode of The AJP-Heart and Circ Podcast, Consulting Editor Dr. Kristine DeLeon-Pennell (Medical University of South Carolina) interviews two authors about their two articles published recently in AJP-Heart and Circulatory Physiology. Dr. Laurel Grisanti (University of Missouri, Columbia) discussed her study (Tanner et al.) on the important role for β2-adrenergic receptor expression on immune cells in the development of heart failure in response to chronic catecholamine elevation. Using a chronic isoproterenol infusion model of heart failure, Dr. Grisanti and co-authors concluded that the immune cell expression of β2-adrenergic receptor is an important contributor to the detrimental responses seen with chronic elevations in catecholamine. The macrophage populations lacking β2-adrenergic receptor largely retained their reparative phenotype and failed to illicit pro-inflammatory macrophage recruitment. Dr. Petra Eder-Negrin (University Hospital, Würzburg) discussed her work (Cellini et al.) in context of Dr. Grisanti's study, underscoring the mechanistic link between sodium potassium -ATPase and β-adrenergic stimulation in the post-MI heart. Eder-Negrin and co-authors found that sodium potassium ATPase alpha 2 overexpressing cardiomyocytes are a crucial adaption, providing an important functional reserve for the heart to cope with chronic stress more efficiently. Sodium potassium ATPase alpha 2 overexpression could be an alteration to attenuate heart failure. How do these research studies connect? Listen now.

 

Miles A. Tanner, Charles A. Maitz, and Laurel A. Grisanti Immune cell β2-adrenergic receptors contribute to the development of heart failure Am J Physiol Heart Circ Physiol, published September 15, 2021. DOI: 10.1152/ajpheart.00243.2021

 

Antonella Cellini, Dorina Höfler, Paula A. Arias-Loza, Sandra Bandleon, Tanja Langsenlehner, Michael Kohlhaas, Christoph Maack, Wolfgang R. Bauer, and Petra Eder-Negrin The α2-isoform of the Na+/K+-ATPase protects against pathological remodeling and β-adrenergic desensitization after myocardial infarction Am J Physiol Heart Circ Physiol, published September 15, 2021. DOI: 10.1152/ajpheart.00808.2020

Estradiol and Endothelin Receptors

Is the loss of endothelin-B receptor mediated vasodilation in women after menopause due to aging or the decline in estradiol that occurs with menopause? Associate Editor Dr. Jason Carter (Montana State University) interviews senior author Megan Wenner (University of Delaware) and content expert Lacy Alexander (Pennsylvania State University) about the work by Wenner and co-authors to isolate and study specific effects of estradiol on the regulation of the ETB receptor. Shoemaker et al. enrolled young women in their study and utilized an endogenous hormone suppression with estradiol add-back experimental design to eliminate changes related to aging and other sex hormones. Wenner and collaborators then measured microvascular endothelial function using laser Doppler flowmetry while perfusing an antagonist for the ETB receptor via intradermal microdialysis fiber, a technique pioneered by Lacy Alexander. The authors found that when estradiol is present, the ETB receptor mediates vasodilation. However, when estradiol is absent or suppressed, ETB-mediated dilation is lost. Bottom line: changes in estradiol regulate the function of this ETB receptor. What is the clinical relevance of this work for women’s health, in particular related to endometriosis, premature ovarian failure, and other pathophysiological conditions related to dysregulated sex hormones? Listen to learn more about this fascinating study and its implications on women’s overall cardiovascular health.

 

Leena N. Shoemaker, Katherine M. Haigh, Andrew V. Kuczmarski, Shane J. McGinty, Laura M. Welti, Joshua C. Hobson, David G. Edwards, Ronald F. Feinberg, and Megan M. Wenner ETB receptor-mediated vasodilation is regulated by estradiol in young women
Am J Physiol Heart Circ Physiol, published September 3, 2021.
DOI: 10.1152/ajpheart.00087.2021

Left Ventricular Dyssynchrony in Young Bodybuilders

Is cardiac remodeling associated with an increase in left ventricular dyssynchrony and post-systolic shortening in young bodybuilders using anabolic-androgenic steroids? Guest Host Brady Holmer (University of Florida) interviews lead author Stéphane Nottin (Avignon University) and content expert Austin Robinson (Auburn University) to get the answers. The groundbreaking work by Grandperrin et al. is the first study to investigate the presence of LV dyssynchrony in strength-trained male athletes using anabolic-androgenic steroids. Black-market steroids are illegal in most sports, yet easily available to athletes on the internet. It is well documented in the literature that use of anabolic-androgenic steroids by strength-trained athletes leads to deleterious cardiac hypertrophy with non-reversible myocardial dysfunction. The authors studied three groups: 1) young male bodybuilders who self-reported substantial use of anabolic-androgenic steroids; 2) young male bodybuilders who self-reported to have never used anabolic-androgenic steroids; 3) young untrained control subjects. Nottin and co-authors evaluated regional strains via resting echocardiography, and found that the group of young male bodybuilders who reported substantial steroid use showed increased LV mechanical dispersion, which correlated with increased LV mass and LV post-systolic shortening. Our experts discuss long term cardiovascular risks to anabolic-androgenic steroid users, as well as future directions and unique techniques needed to study female bodybuilders using anabolic-androgenic steroids. This episode is a must-listen for athletes, coaches, and exercise physiologists alike. Listen now.

 

Antoine Grandperrin, Iris Schuster, Thomas Rupp, Omar Izem, Philippe Obert, and Stéphane Nottin Left ventricular dyssynchrony and post-systolic shortening in young bodybuilders using anabolic-androgenic steroids Am J Physiol Heart Circ Physiol, published August 25, 2021. DOI: 10.1152/ajpheart.00136.2021

Behind the Bench Episode 10

Allow us to introduce you to Tommy Martin, a trainee in The Kirk Lab at Loyola University Chicago, who is scheduled to defend his PhD thesis in October 2021. Tommy is first author on a recently published AJP-Heart and Circ article, which is co-authored by Jonathan Kirk, an Associate Editor for AJP-Heart and Circ, and a founding member of our Behind the Bench podcast crew. Tommy has a story that will resonate with trainees and early career researchers: he was vacillating between going to medical school and getting a PhD. His interview with the very personable and enthusiastic Jonathan Kirk was the deciding factor to take the fork in the road that led to graduate school for a PhD in cardiovascular research. Our intrepid Behind the Bench co-hosts Lisandra de Castro Brás (East Carolina University) and Charlotte Usselman (McGill University) interview Tommy about life in the lab as a would-be medical student, learning how to use a pipette for the first time, his best advice to trainees for how to nail the post-doc interview process, and the drive and commitment necessary to pursue success in science. We also get the inside scoop about all things Jonathan Kirk (that beard!), and along the way we manage to discuss BAG3 protein expression in sarcomeric proteins in heart failure. Tommy Martin is engaging, sharp and clearly a rising star in cardiovascular research. Listen now, and don’t miss the bonus outtake after the credits.

 

Thomas G. Martin, Sara Tawfik, Christine S. Moravec, Toni R. Pak, Jonathan A. Kirk BAG3 expression and sarcomere localization in the human heart are linked to HSF-1 and are differentially affected by sex and disease Am J Physiol Heart Circ Physiol, published May 26, 2021.
DOI: 10.1152/ajpheart.00419.2020

Behind the Bench Episode 9

How does a single intriguing patient encounter lead to a clinical research career investigating extreme premature birth history and increased risk of cardiopulmonary complications later in life? In this new episode of Behind the Bench with AJP-Heart and Circ, co-hosts Lisandra de Castro Brás (East Carolina University) and Charlotte Usselman (McGill University) interview Kara Goss (University of Texas Southwestern) about the fascinating study by Corrado et al. Admittedly inspired by her own experience as a mother to two children, both of whom were born prematurely, our producer Kara Hansell Keehan wanted to dig deeper into this latest work by Goss and co-authors. An early inspiration for Goss was her clinical rotation in the NICU, yet she followed a different clinical path into adult critical cardiopulmonary care. It was ultimately a single encounter with an older patient in acute cardiopulmonary distress who had, as Goss uncovered, a preterm birth history, that changed her career path. Thus, a research career was born (pun intended). Why did Goss and co-authors find right ventricular, but not left ventricular, dysfunction in this former preemie adult cohort? Is exercise the key to mitigating the effects of this right ventricular function? This podcast episode is simply fascinating, so listen now.

 

Philip A. Corrado, Gregory P. Barton, Christopher J. Francois, Oliver Wieben, and Kara N. Goss Sildenafil administration improves right ventricular function on 4D flow MRI in young adults born premature Am J Physiol Heart Circ Physiol, published May 20, 2021. DOI: doi.org/ 10.1152/ajpheart.00824.2020