AJP-Heart and Circulatory Physiology Podcast

Racial & Socioeconomic Determinants of the Cardiac Epigenome

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

Macrophage Regulation of Matrix Remodeling

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.
DOI: doi.org/10.1152/ajpheart.00056.2021

Behind the Bench Episode 8

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

Perivascular Nerve Dysfunction in Inflammatory Bowel Disease

What is the effect of vascular function in the pathogenesis of Inflammatory Bowel Disease (IBD)? According to Centers for Disease Control data, there are approximately 3 million people with IBD in the U.S. population, with more than 7,000 new cases of IBD diagnosed every year. IBD patients are at greater risk for developing cardiovascular disease compared to age-matched peers. Listen as Consulting Editor Camilla Wenceslau (University of Toledo) interviews senior author Erika Boerman (University of Missouri) and expert Pooneh Bagher (Texas A&M Health Science Center) about this novel study by Norton et al. Decreased blood flow to the gut is a diagnostic hallmark of IBD, and sensory neurotransmitters calcitonin gene-related peptide (CGRP) and substance P are considered biomarkers of IBD. Using pressure myography to study mesenteric arteries in an interleukin-10 knockout mouse model, Boerman and collaborators investigated the activation of perivascular sensory nerves, which control gastrointestinal tract blood flow. When Boerman and co-authors first blocked substance P receptors and then stimulated sensory nerves, sensory vasodilation was rescued in the IBD vessels. A surprising finding was that the substance P pathway seemed to interfere with the CGRP pathway, preventing normal sensory vasodilation. Does Boerman estimate that an influx of immune cells into the gut, interacting with sensory neurotransmitters, is a factor in IBD pathogenesis? Listen as these experts discuss the mechanisms that impact reduced blood flow and tissue ischemia which leads to IBD, and the unanswered questions which may help to unravel the link between IBD and cardiovascular disease.

 

Charles E. Norton, Elizabeth A. Grunz-Borgmann, Marcia L. Hart, Benjamin W. Jones, Craig L. Franklin, Erika M. Boerman Role of perivascular nerve and sensory neurotransmitter dysfunction in inflammatory bowel disease   Am J Physiol Heart Circ Physiol, published April 22, 2021. DOI: doi.org/10.1152/ajpheart.00037.2021

Inorganic Arsenic Induces Cardiac Hypertrophy

Does inorganic arsenic in drinking water lead to cardiac hypertrophy? In this episode, host Dominic Del Re (Rutgers New Jersey Medical School) interviews lead author Mark Kohr (Johns Hopkins University) and expert Nicole Purcell (Huntington Medical Research Institutes) about the new study by Kohr and colleagues, which studied the effects of an environmentally-relevant level of inorganic arsenic in the drinking water of male and female mice. Kabir et al were inspired by the public health crisis in Bangladesh caused by arsenic contaminated drinking water. In their study the authors found increased systolic blood pressure, increased LV mass and wall thickness, and induction of the fetal gene program in male mice, but not in female mice. Kohr and co-authors found arsenic promoted calcineurin NFAT signaling but did not disrupt nitric oxide-dependent mechanisms of cardioprotection. The authors uncover sex differences in the cardiovascular response to arsenic, as well as a clear mechanistic link between this environmental risk factor – arsenic in drinking water – and cardiac pathology. Can this work be translated on a larger scale to inspire everyday interventions to mitigate adverse environmental effects on human heart health? To find out, listen now.

 

Raihan Kabir, Prithvi Sinha, Sumita Mishra, Obialunanma V. Ebenebe, Nicole Taube, Chistian U. Oeing, Gizem Keceli, Rui Chen, Nazareno Paolocci, Ana Rule, Mark J. Kohr Inorganic arsenic induces sex-dependent pathological hypertrophy in the heart Am J Physiol Heart Circ Physiol, published March 24, 2021. DOI: 10.1152/ajpheart.00435.2020

Microvascular Function Following Preeclampsia

We recorded our latest episode on International Women’s Day 2021, and the topic is particularly relevant and fitting. Host Jessica Faulkner (Augusta University) interviewed authors Graeme Smith and Logan Barr (both at Queen’s University), as well as expert Junie Paula Warrington (University of Mississippi Medical Center) about a new study by Barr et al. Using laser speckle contrast imaging and iontophoresis, the authors assessed microvascular function in women five years postpartum in both normal pregnancy and preeclamptic pregnancy cohorts. The authors also characterized hypertensive pregnancies as either mild or severe preeclampsia, a novel stratification of patients which helped identify unique functional alterations in the vasculature of the severely preeclamptic women compared to the mildly preeclamptic women. Why do the authors hypothesize that nitric oxide depletion and oxidative stress in the preeclamptic pregnancies are the culprits behind the endothelial dysfunction seen in these patients? What role does body mass index (BMI) play in the postpartum cardiovascular effects of preeclampsia? Listen to find out.

 

Logan C. Barr, Jessica Pudwell, Graeme N. Smith Postpartum microvascular functional alterations following severe preeclampsia Am J Physiol Heart Circ Physiol, published January 22, 2021. DOI: 10.1152/ajpheart.00767.2020

E-cigarettes, Aldehydes and Endothelial Dysfunction

What are the cardiovascular effects of propylene glycol and vegetable glycerin (PG:VG) and saturated aldehydes used in electronic cigarettes? Guest Editor Loren Wold (The Ohio State University) interviews senior author Daniel Conklin (University of Louisville) and expert Mark Olfert (West Virginia University) about the latest study by Jin et al., which investigated the base liquid in E-cigarettes in the absence of nicotine and flavorings. Conklin and co-authors exposed male and female mice to the individual components of the E-cigarette aerosol cloud (PG:VG-derived aerosol, formaldehyde gas, acetaldehyde gas) and compared their results to filtered air. The authors found mice exposed to PG:VG and formaldehyde gas showed increased endothelial dysfunction, a key biomarker of chronic cardiovascular disease risk. The authors also found that female mice were more sensitive to each of the exposure conditions than male counterparts. Does this indicate that female mice are a sensitive and useful model for exposure to environmental inhalants? Do the authors think that heat-not-burn E-cigarettes may be an alternative to E-cigs using PG:VG base liquid? Listen as our experts discuss where we go from here.

 

Lexiao Jin, Jordan Lynch, Andre Richardson, Pawel Lorkiewicz, Shweta Srivastava, Whitney Theis, Gregg Shirk, Alexis Hand, Aruni Bhatnagar, Sanjay Srivastava, Daniel J. Conklin Electronic Cigarette Solvents, Pulmonary Irritation and Endothelial Dysfunction:Role of Acetaldehyde and Formaldehyde Am J Physiol Heart Circ Physiol, published February 5, 2021. DOI: doi.org/10.1152/ajpheart.00878.2020

Binge Drinking, Sleep and Sympathetic Activity

How well do we understand the underlying mechanisms of the cardiovascular consequences associated with binge drinking at night? Consulting Editor Nisha Charkoudian (U.S. Army Research Institute of Environmental Medicine) interviews lead author Jason Carter (Montana State University) and expert Craig Steinback (University of Alberta) about the latest work by Greenlund et al. While many researchers have investigated binge drinking in a laboratory setting, most of these studies are conducted during daytime hours. In contrast, Carter and co-authors aimed to mimic real-life alcohol consumption habits in their pragmatic study design, which interrogated the effects of binge drinking on sleep, as well as on sympathetic activity the following morning. Carter and his team found that study participants had increased cardiovascular stress, measured by increased heart rate and sympathetic activity, and decreased control of blood pressure. While the authors designed their study prior to the SARS-CoV2 pandemic, their findings are more relevant now than ever before. Listen as we touch on the future directions of this work, including exploring sex differences in alcohol consumption patterns and metabolization, and cognitive aspects of binge drinking.

 

Ian M. Greenlund, Hannah A. Cunningham, Anne L. Tikkanen, Jeremy A. Bigalke, Carl A. Smoot, John J. Durocher, and Jason R. Carter Morning sympathetic activity after evening binge alcohol consumption Am J Physiol Heart Circ Physiol, published January 15, 2021. DOI: 10.1152/ajpheart.00743.2020

Membrane Proteomic Profiling of the Heart

What are the latest technological advances for studying cell membrane proteins? Podcast host Lisandra de Castro Brás (East Carolina University) interviews lead author Tony Gramolini (University of Toronto) and expert Sarah Parker (Cedars-Sinai Medical Center) about the latest Review by Lee et al, which outlines challenges in the development of heart disease therapies related to the limited number of functional target proteins in cell surface receptors. The authors also examine potential limitations and workarounds for analyzing hydrophobic membrane proteins, discuss the importance of spatial location during sample harvesting, and review the potential of mass spectrometry tools for generation of robust and ample data. Our experts discuss a wide array of cutting-edge proteomic analysis tools, including tissue cytof, single-cell proteomics, and mass spectrometry, and give special attention to techniques for interrogating low-abundant proteins. This leads to an in-depth exchange about data reporting in research articles. What do the authors think is on the horizon for advanced interrogation of post-translational modifications and integrated AI-based analysis of the vast amounts of data produced by proteomic profiling? Listen to find out.

 

Shin-Haw Lee, Da Hye Kim, Uros Kuzmanov, Anthony O. Gramolini Membrane proteomic profiling of the heart: past, present, and future Am J Physiol Heart Circ Physiol, published January 15, 2021. DOI: doi.org/10.1152/ajpheart.00659.2020

Aerosolized Nicotine and Cardiovascular Control

What are the acute effects of inhaling nicotine through an e-cigarette on cardiovascular neural regulation? In this episode Guest Editor Loren Wold (The Ohio State University) interviews lead author William Cooke (Michigan Technological University) and expert Ted Wagener (The Ohio State University) about the latest research by Gonzalez and Cooke on this timely topic. As more and more studies show that e-cigarettes do carry their own distinct health risks, Gonzalez and Cooke recruited naïve e-cigarette users, otherwise known as “never smokers,” for their e-cigarette study. The authors observed an acute increase in arterial pressure in study participants, which was associated with a blunting of peripheral sympathetic activity. Why is this important? The authors believe that there could be long term effects on the heart, including increases of heart rate and blood pressure, which could lead to pre-hypertension or chronic hypertension for non-smokers who opt to use electronic cigarette devices. Our experts unpack the implications of this unique study, the potential for researchers to separate effects of inhaled nicotine from effects of inhaled combustible tobacco toxicants, and what new federal guidelines may be forthcoming from the Food and Drug Administration (FDA) for e-cigarette devices in the coming year. Listen now to find out more.

 

Joshua Eric Gonzalez and William Harold Cooke Acute effects of electronic cigarettes on arterial pressure and peripheral sympathetic activity in young non-smokers  Am J Physiol Heart Circ Physiol, published November 8, 2020. DOI: doi.org/10.1152/ajpheart.00448.2020