AJP-Heart and Circulatory Physiology Podcast

Vascular Function During the Estrous Cycle

When Dr. Ashley Walker (University of Oregon) began to study sex differences with vascular aging and cognitive decline, she and her team went to the literature for guidance on research study design to account for the confounding variable of estrous cycle in young female mice. Problem: There were no recommendations in the literature. Solution: The Walker Lab got to work. In our latest episode, Dr. Amanda LeBlanc (University of Louisville) interviews lead author Dr. Ashley Walker and first author Ms. Mackenzie Kehmeier (University of Oregon), along with expert Dr. Sarah Lindsey (Tulane University) about the novel study by Kehmeier et al. – the first of its kind – to show that the impact of estrogen on vascular stiffness changes with each day of the female mouse estrous cycle. The authors found that estrous phase was associated with lower in vivo large artery stiffness in mice, but ex vivo resistance artery endothelial function was not different between estrous cycle phases. Kehmeier et al. determined that estrogen receptor expression is modulated by the estrous cycle in an artery dependent manner, which means that estrous cycle phase in young female mice should be considered when measuring in vivo arterial stiffness. What techniques do the authors recommend for other investigators to best determine accurate staging of the estrous cycle? Listen to find out.

 

Mackenzie N. Kehmeier, Bradley R. Bedell, Abigail E. Cullen, Aleena Khurana, Holly J. D’Amico, Grant D. Henson, Ashley E. Walker In vivo arterial stiffness, but not isolated artery endothelial function, varies with the mouse estrous cycle Am J Physiol Heart Circ Physiol, published October 14, 2022. DOI: 10.1152/ajpheart.00369.2022

Sm22alpha in Keratinocytes

Have you ever had an experimental design deviate from expectations? Well, this episode is for you. Associate Editor Dr. Keith Brunt (Dalhousie University) interviews Deputy Editor Dr. Zamaneh Kassiri (University of Alberta) about her recently published article by Hu et al., along with content expert Dr. Joshua Man ( Tufts Medical Center), to discuss how unexpected results and negative findings can, in and of themselves, lead to new discoveries. Kassiri and co-authors used a Cre/lox system to study the role of disintegrin and metalloproteinase-17 (Adam17) in smooth muscle cells (SMC) in a mouse model of atherosclerosis. LDL-deficient mice that consumed a high fat diet had normal skin. However, mice with floxed alleles of Adam17 driven by Sm22alpha developed severe skin lesions. The loss of gene function and Sm22alpha expression was apparent in keratinocytes. Adam17 deletion by a different SMC driver, Myh11-Cre, did not result in skin lesions in the same atherosclerosis model. Staying true to the expression that experience is what you get when you don’t get what you want, Hu et al. published their results in the hopes of helping other labs and animal care & use committees avoid similar pitfalls. What are the potential ramifications for cardiovascular researchers, keratinocyte biologists, and dermatologists? Listen and find out.

 

Mei Hu, Sho Hiroyasu, David J. Granville, Zamaneh Kassiri Implications of Sm22alpha-Cre expression in keratinocytes and unanticipated inflammatory skin lesion in a model of atherosclerosis  Am J Physiol Heart Circ Physiol, published August 31, 2022. DOI: 10.1152/ajpheart.00325.2022

VO2 Kinetics and Chronotropic Responses After Severe COVID-19

Why do many severe COVID-19 survivors experience exercise intolerance as a lingering consequence of their viral infection? In this episode, Guest Editor Dr. Tiago Peçanha (Manchester Metropolitan University) interviewed lead author Dr. Hamilton Roschel (University of Sao Paulo) and expert Dr. John Durocher (Purdue University Northwest) about the latest study by Longobardi et al., which investigated the impact of previous severe COVID-19 infection on cardiorespiratory responses to a maximal exercise test. The authors enrolled survivors of severe COVID-19 who had previously been admitted to an intensive care unit during the acute phase of their illness in this cross-sectional study within a randomized controlled trial. The authors found that VO2 kinetics were significantly impaired at the onset and recovery phases of the exercise protocol in the COVID survivors. What do these experts think about the central and peripheral factors underlying the exertional intolerance and chronotropic incompetence in COVID survivors? Listen now.

 

Igor Longobardi, Danilo Marcelo Leite do Prado, Karla Fabiana Goessler, Matheus Molina Meletti, Gersiel Nascimento de Oliveira Júnior, Danieli Castro Oliveira de Andrade, Bruno Gualano, Hamilton Roschel Oxygen uptake kinetics and chronotropic responses to exercise are impaired in survivors of severe COVID-19 Am J Physiol Heart Circ Physiol, published September 2, 2022. DOI: 10.1152/ajpheart.00291.2022

Behind the Bench Episode 13

In our latest episode of Behind the Bench from AJP-Heart and Circ, co-hosts Dr. Tommy Martin and Dr. Charlotte Usselman interview bioengineer and first author Dr. Amy Garrett. Dr. Garrett joined the Auckland Bioengineering Institute in 2016, where she completed a Masters in Engineering followed by a PhD. After joining the cardiac energetics group for her post-doc, Dr. Garrett embarked on a research journey tackling the development of the Windkessel loading system for work-loop contractions. What’s that, you’re wondering? The work-loop calorimeter is an experimental device fine-tuned by the Auckland Bioengineering Institute over the past 20 years. The device performs stress-length work-loops on cardiac trabeculae. It is both fascinating and complicated. Good news: Dr. Garrett explains everything! Find out more about her scientific journey, and why Windkessel loaded loops are important. Listen now.

Amy S. Garrett, Denis S. Loiselle, Andrew J. Taberner, June-Chiew Han Slower shortening kinetics of cardiac muscle performing Windkessel work-loops increase mechanical efficiency Am J Physiol Heart Circ Physiol, published August 31, 2022. DOI: 10.1152/ajpheart.00074.2022

COVID-19 and Diabetes

What is a cytokine storm in COVID-19 patients and how does it adversely affect organ systems in diabetes patients? In our latest episode, Associate Editor Dr. Keith Brunt (Dalhousie University) interviews lead author Dr. Dinender Singla (University of Central Florida) and expert Dr. Mark Chappell (Wake Forest University) about the new Review by Narasimhulu and Singla on the pathophysiology of the SARS-CoV2 virus as it relates to diabetes. As we now know, the virus enters cells through the angiotensin converting enzyme 2 receptors, which is especially concerning for patients with pre-existing cardiovascular complications and co-morbidities such as diabetes, given that renin-angiotensin system is a driving force of cardiovascular disease. In this insightful and wide-ranging interview, our experts discuss viral variance, sex differences, the need for more sophisticated pre-clinical models, long COVID, and implications for co-morbidity management. Where does the field go from here? Read, listen, learn.

 

Chandrakala Aluganti Narasimhulu and Dinender K. Singla Mechanisms of COVID-19 pathogenesis in diabetes  Am J Physiol Heart Circ Physiol, published August 4, 2022. DOI: 10.1152/ajpheart.00204.2022

Save Hearts, Improve Efficiency

How do the 3 Rs of Research – Refinement, Reduction, Replacement – factor into a methodological paper regarding a novel quantitative method for using an electrocardiogram to determine which animals have infarcts that reflect successful coronary ligation? Listen as Consulting Editor Dr. Ganesh Halade (University of South Florida) interviews lead author and Consulting Editor Dr. Kristine DeLeon-Pennell (Medical University of South Carolina) and content expert Dr. Corey Reynolds (Merck & Co.) about the recent work by Broughton et al. What started as an internal project to improve The DeLeon-Pennell Lab’s surgical success grew into a research article published as part of a Call for Papers on Innovation in Improving Rigor and Reproducibility in Cardiovascular Research. The DeLeon-Pennell Lab was interested in streamlining infarct size between lab members, students, and technicians during the surgical procedures used for their mouse studies. Aiming for a threshold of 35% infarct size, the DeLeon-Pennell Lab wanted to move beyond looking only at the elevation of the T wave to confirm infarct size. To do so, Broughton et al. designed a new ECG method that provides real-time feedback during the procedure. Broughton et al. found that area under the QRS curve is stronger for predicting successful MI surgeries with an infarct size greater than 35%. This new method will ultimately allow researchers to reduce the time spent performing surgical experiments and the overall number of animals used. Listen now to find out more.

 

Philip Broughton, Miguel Troncoso, Alexa Corker, Alexus Williams, Dawson Bolus, Gualberto Munoz, Caroline McWhorter, Hallie Roerden, Penny Huebsch, and Kristine Y. DeLeon-Pennell Riding the wave: a quantitative report of electrocardiogram utilization for myocardial infarction confirmation Am J Physiol Heart Circ Physiol, published August 3, 2022. DOI: doi.org/10.1152/ajpheart.00201.2022

Daylight Saving Time and Cardiovascular Risk

Is it bad for our cardiovascular health to “spring forward” into Daylight Saving Time? On March 15, 2022, the U.S. Senate passed the Sunshine Protection Act, which aims to make Daylight Saving Time permanent and eliminate bi-annual seasonal clock changes in the spring and fall. In this episode, Consulting Editor Dr. Austin Robinson (Auburn University) interviews lead author and Associate Editor Dr. Jason Carter (Montana State University) and expert Dr. Josiane Broussard (Colorado State University) about a Perspective by Carter et al. which unpacks the negative impacts on overall cardiovascular health, as well as the increased risks of adverse cardiovascular events associated with changing our clocks between Standard Time and Daylight Saving Time. While the proposed Sunshine Protection Act legislation appears to offer a solution—instituting Daylight Saving Time as the permanent time – both the American Academy of Sleep Medicine and the Society for Research on Biological Rhythms argue that the healthier choice is Standard Time. Studies have shown that the shift to Daylight Saving Time results in increased incidence of myocardial infarction, stroke, and hospital admissions attributed to atrial fibrillation. In addition, the decrease in morning light with Daylight Saving Time has potential adverse effects on mental health, because morning sunshine plays a critical role in synchronizing our internal clocks to avoid circadian misalignment. Could shifting 30 minutes rather than 60 minutes be a reasonable compromise? Listen now to find out.

 

Jason R. Carter, Kristen L. Knutson, Babak Mokhlesi Taking to “heart” the proposed legislation for permanent daylight saving time Am J Physiol Heart Circ Physiol, published June 13, 2022. DOI: doi.org/10.1152/ajpheart.00218.2022

SRPK1 Eye Drops as a Treatment for Diabetic Retinopathy

The eyes are the window to the soul, as the old saying goes, but are the eyes also the window to cardiovascular disease? Diabetic retinopathy is a common diabetic microvascular disease and a leading cause of blindness in diabetes patients worldwide. Defects in the blood-retinal barrier caused by increased production of vascular endothelial growth factor-A isoforms promote angiogenesis and permeability. Listen as Consulting Editor Dr. Shawn Bender (University of Missouri, Columbia) interviews first author Dr. Naseeb Malhi (City of Hope National Medical Center), senior author Dr. David Bates (University of Nottingham), and expert Dr. Jerome Breslin (University of South Florida) about the new study by Malhi et al, which investigated whether serine-arginine-rich protein kinase-1 (SRPK1) inhibition can attenuate the pathophysiology of diabetic retinopathy. The authors conducted a combination of mechanistic in vitro studies using human retinal pigment epithelial cells and studies in type 1 diabetic rats to investigate whether SRPK1 is activated in diabetes, and whether an SRPK1 inhibitor (SPHINX31) switches VEGF splicing in diabetic retinopathy to prevent increased vascular permeability into the retina. The novel intervention design of delivering the SRPK1 inhibitor via eyedrop in the authors’ diabetic rat model was used preventatively at the outset of the diabetes phenotype. Does this unique treatment modality offer promise for treating established diabetic retinopathy? Listen and learn.

 

Naseeb K. Malhi, Claire L. Allen, Elizabeth Stewart, Katherine L. Horton, Federica Riu, Jennifer Batson, Winfried Amoaku, Jonathan C. Morris, Kenton P. Arkill, David O. Bates Serine-arginine-rich protein kinase-1 inhibition for the treatment of diabetic retinopathy Am J Physiol Heart Circ Physiol, published May 10, 2022. DOI: 10.1152/ajpheart.00001.2022

Behind the Bench Episode 12

This episode of Behind the Bench with AJP-Heart and Circ is full of connections. Returning co-host Dr. Charlotte Usselman is joined by her new co-host Dr. Tommy Martin. We first met Tommy when we interviewed him last year for Behind the Bench episode 10 as a trainee in the lab of AJP-Heart and Circ Associate Editor Dr. Jonathan Kirk. Jonathan was the original co-host of Behind the Bench along with Dr. Lisandra de Castro Brás. Speaking of Jonathan and Lis… big shout out to the original Behind the Bench co-hosts for their stellar insights and witty humor! Fast forward to the proverbial passing of the Behind the Bench microphone to Charlotte and Tommy and their wide-ranging interview with Dr. Jody Greaney, lead author of a new study interrogating vascular dysfunction as one mechanism, of the many potential mechanisms, linking major depressive disorder to CV disease risk. Greaney and co-authors investigated upstream mechanisms of vascular dysfunction and increased vascular superoxide by targeting inflammation with short-term salicylate treatment in a young adult population with major depressive disorder and found that this treatment did improve microvascular endothelium-dependent dilation. Listen as Jody discusses how she persevered with her small proof-of-concept study through finishing her post-doc, obtaining a faculty position, navigating the start-up her own lab, pandemic related interruptions to basic research, and peer reviewer comments that seemed daunting to overcome. Could depression, at its core, be characterized as an inflammatory disease? Are you at a critical career fork in the road and need some insight? Listen now.

 

Jody L. Greaney, Erika F. H. Saunders, Lacy M. Alexander Short-term salicylate treatment improves microvascular endothelium-dependent dilation in young adults with major depressive disorder
Am J Physiol Heart Circ Physiol, published April 14, 2022. DOI: 10.1152/ajpheart.00643.2021

Vascular Function, Mortality and COVID-19

First, a thank you to frontline healthcare workers, clinical researchers, and one determined master’s student Michelle Cristina-Oliveira of the Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo for their bravery and dedication to science and medicine!
In this episode we bring you a conversation between Associate Editor Dr. Jason Carter (Montana State University), lead author Dr. Tiago Pecanha (Universidade de São Paulo, and Manchester Metropolitan University), and expert Dr. Paul Fadel (The University of Texas at Arlington). From June 2020 to May 2021 first author Michelle Cristina-Oliveira screened over 600 patients at the height of the COVID-19 pandemic in São Paulo, Brazil in order to enroll 211 COVID-19 patients within 72 hours of hospital admission. The authors sought to determine whether brachial artery flow-mediated dilation and carotid intima-media thickness measured upon hospital admission were associated with acute outcomes in hospitalized COVID-19 patients. Based on initial case reports, Cristina-Oliveira et al. felt that the endothelium could be an important target for SARS-CoV2. The authors hypothesized that measuring markers of endothelial function and atherosclerosis upon hospital admission could provide critically important information about potential risks of mortality, admission to ICU, and requirement for mechanical ventilation. Did the authors find that endothelial function and atherosclerosis were useful in predicting major clinical outcomes of COVID-19 patients? This study lends further insight into understanding the role of reduced flow mediated dilation in mediating the negative effects of COVID on cardiovascular health. Listen to find out why.

 

Michelle Cristina-Oliveira, Kamila Meireles, Saulo Gil, Fábio Cavalcante Assis, João Carlos Geber-Júnior, Samuel Katsuyuki Shinjo, Heraldo Possolo de Souza, Alfredo Nicodemos Cruz Santana, Paul A. Swinton, Luciano F. Drager, Bruno Gualano, Hamilton Roschel, and Tiago Peçanha Carotid intima-media thickness and flow-mediated dilation do not predict acute in-hospital outcomes in patients hospitalized with COVID-19 Am J Physiol Heart Circ Physiol, published April 22, 2022. DOI: 10.1152/ajpheart.00026.2022