AJP-Heart and Circulatory Physiology Podcast

Angiogenic Exosomes from Vascular Progenitor Cells

Where did the search to find exosome donor cells lead the authors of the new study by Johnson et al? Editor in Chief Irving H. Zucker (University of Nebraska Medical Center) interviews authors Dong Liu (Morehouse School of Medicine) and Takerra Johnson (National Institutes of Health/ National Eye Institute), along with content expert Jean-Pyo Lee (Tulane University), about this novel study which utilized induced vascular progenitor cells as exosome donor cells to promote angiogenesis. The authors determined that secretion is more important to endothelial cells than differentiation, because secretion includes growth factors, cytokines, and exosomes. Compared to rat aortic endothelial cells, induced vascular progenitor cells have a greater secretion of exosomes. Johnson et al found that iVPCs promoted angiogenesis in a rat hindlimb ischemia model. What did the authors uncover when they investigated the microRNA cargo carried by iVPC exosomes? Listen and learn more.

 

Takerra K. Johnson, Lina Zhao, Dihan Zhu, Yang Wang, Yan Xiao, Babayewa Oguljahan, Xueying Zhao, Ward G. Kirlin, Liya Yin, William M. Chilian, and Dong Liu Exosomes derived from induced vascular progenitor cells promote angiogenesis in vitro and in an in vivo rat hindlimb ischemia model Am J Physiol Heart Circ Physiol, published October 1, 2019. DOI: doi.org/10.1152/ajpheart.00247.2019

“Fit-for-Purpose” Approach to Antibody Validation

Why is it critical for researchers to take the time to validate their antibodies and protocols used in specific applications? Associate Editor Crystal Ripplinger (University of California Davis) interviews lead author Rebekah Gundry (University of Nebraska Medical Center) and Deputy Editor Merry Lindsey (University of Nebraska Medical Center) about this unique Perspective by Matthew Waas and Rebekah Gundry that proposes an approach for antibody validation for flow cytometry assessment of stem cell-derived cardiomyocytes used in cardiovascular physiology and translational research. We address the rigor and reproducibility hurdles researchers face when standardizing immunophenotyping protocols, as well as the challenges of including sufficient experimental details in manuscripts when faced with publisher-mandated manuscript word counts. Waas and Gundry call for moving away from the term “validation” and instead adopting “fit-for-purpose.” How does this fit with the concept of “trust but verify” and new NIH antibody authentication documents required for grant submissions? Listen now.

 

Matthew Waas and Rebekah L. Gundry A call to adopt a 'fit-for-purpose' approach to antibody validation for flow cytometry analyses of stem cell models and beyond Am J Physiol Heart Circ Physiol, published October 23, 2019. DOI: doi.org/10.1152/ajpheart.00347.2019

Spinal Cord Stimulation Blunts Dorsal Root Transduction of the Ischemic Ventricle

Can neuromodulation be used to change the sensory transduction of the ischemic ventricle? To answer this question, Editor-in-Chief Dr. Irving H. Zucker (University of Nebraska Medical Center) interviewed lead author Jeffrey Ardell ( University of California Los Angeles) and content expert Marc Kaufman (Pennsylvania State University) about the new work by Salavatian et al. Ardell and co-authors found that preemptive spinal cord stimulation can reduce the afferent signal coming from the ischemic ventricle. Was this a result of a change in substrate utilization in the heart or was this “silent ischemia”? Does this spinal cord stimulation work by Ardell and collaborators have the potential to translate to reducing pain for patients with angina? Don’t miss the extra “off the record” commentary at the end to find out.

 

Siamak Salavatian, Sarah M. Ardell, Mathew Hammer, David Gibbons, J. Andrew Armour, Jeffrey L. Ardell Thoracic spinal cord neuromodulation obtunds dorsal root ganglion afferent neuronal transduction of the ischemic ventricle Am J Physiol Heart Circ Physiol, published November 4, 2019. DOI: doi.org/10.1152/ajpheart.00257.2019

Guidelines for Evaluating Myocardial Cell Death

It’s well known that myocardial cell death leads to cardiac remodeling and heart failure. It is, however, less well known exactly which mechanisms lead to myocyte cell death in the heart. In our latest podcast, Associate Editor Junichi Sadoshima (Rutgers New Jersey Medical School) interviews lead authors Paras Mishra (University of Nebraska Medical Center), Joseph Hill (University of Texas Southwestern Medical Center), Peter Kang (Beth Israel Deaconess Medical Center), James Downey (University of South Alabama) and Takashi Matsui (University of Hawaii at Manoa) about their recent comprehensive Guidelines in Cardiovascular Research article on evaluating myocardial cell death. Listen as our experts—all of whom are global thought-leaders in their individual fields—delve into the 6 main mechanisms of cell death in the heart: apoptosis, ferroptosis, autophagic cell death, necroptosis, MPT-mediated necrosis, pyroptosis, autosis.

 

Paras K. Mishra, Adriana Adameová, Joseph A. Hill, Christopher P. Baines, Peter M. Kang, James Downey, Jagat Narula, Masafumi Takahashi, Antonio Abbate, Hande C. Piristine, Sumit Kar, Shi Su, Jason K. Higa, Nicholas K. Kawasaki, Takashi Matsui Guidelines for evaluating myocardial cell death Am J Physiol Heart Circ Physiol, published October 23, 2019. DOI: doi.org/10.1152/ajpheart.00259.2019

Experimental Design: Survey, Training & Practical Tools

Is it possible for preclinical researchers to improve the quality of their cardiac and metabolic animal studies by incorporating protocols and strategies aimed at reducing bias? Listen as Deputy Editor Merry L. Lindsey (University of Nebraska Medical Center) interviews lead author Julie R. McMullen (Baker Heart & Diabetes Institute) and content expert Lisandra de Castro Brás (East Carolina University) about the study by Weeks et al., the latest article in the AJP-Heart and Circulatory Physiology Cores of Reproducibility in Physiology series. McMullen and co-authors conducted a short survey of preclinical research colleagues about how animal studies were being performed, with a focus on blinding, randomization and allocation concealment. The survey was followed by skills training aimed at improving practices, such as computer-generated methods for randomization and de-identifying drugs and interventions. Why take on this project? By providing basic scientists with tools to correctly randomize animals, and rationale to pre-specify inclusion and exclusion criteria, pre-specify endpoints, and appropriately address negative data, McMullen and collaborators hope to equip investigators with tools and knowledge to remove unconscious bias. This includes the encouragement of team science among smaller labs to allow for improvements in experimental design such as allocation concealment, which requires more personnel. Listen now to learn more.

 

Kate L. Weeks, Darren C. Henstridge, Agus Salim, Jonathan E. Shaw, Thomas H. Marwick, Julie R. McMullen CORP: Practical Tools for Improving Experimental Design and Reporting of Laboratory Studies of Cardiovascular Physiology and Metabolism Am J Physiol Heart Circ Physiol, published July 26, 2019. DOI: doi.org/10.1152/ajpheart.00327.2019

CD161a+ Immune Cells in Cholinergic Hypertension

How do the immune system, nervous system, and renal system interact in the pathogenesis of hypertension? In this podcast Editor in Chief Irving H. Zucker (University of Nebraska Medical Center) interviews lead author Sailesh Harwani (University of Iowa) and content expert Liang Xiao (Vanderbilt University) about the new study by Raikwar et al, which used a spontaneously hypertensive rat model in a pre-hypertensive state to determine the causality of the multi-system components. The study design involved two interventions--complete bi-lateral renal denervation, and ablation of CD161a+ immune cells. The authors found that administering nicotine in the renal denervation group prevented cholinergic hypertension. Blood pressure elevation and renal inflammation were prevented in both the renal denervation and CD161a+ ablation intervention groups by administering nicotine. Does the location of CD161 immune cells at the vertex between the kidneys and immune systems play a pivotal role in how these cells are influenced by the adrenergic and cholinergic nervous systems? Listen and find out.

 

Nandita Raikwar, Cameron Braverman, Peter M. Snyder, Robert A. Fenton, David K. Meyerholz, Francois M. Abboud, and Sailesh C. Harwani Renal denervation and CD161a immune ablation prevent cholinergic hypertension and renal sodium retention Am J Physiol Heart Circ Physiol, published August 20, 2019. DOI: doi.org/10.1152/ajpheart.00234.2019

Attenuation of Coronary Adenosine Dilation by Aldosterone

High plasma aldosterone is an independent risk factor for cardiac mortality, but what is known about the underlying mechanisms linking high levels of aldosterone to cardiac ischemic events? Listen as Consulting Editor Donal O’Leary (Wayne State University) interviews lead author Shawn Bender (University of Missouri & Truman VA) and expert Judy Muller-Delp (Florida State University) about the work led by motivated undergraduate Maloree Khan, which tested the hypothesis that increased plasma aldosterone impairs adenosine-mediated coronary vasodilation. Bender and co-authors found that high plasma aldosterone levels impaired adenosine A2A receptor-mediated dilation, but not adenosine A2B receptor-mediated vasodilation. Using a dose of aldosterone that does not significantly elevate blood pressure, Khan et al observed aldosterone-mediated changes in coronary dilation to adenosine via downregulation of calcium-activated potassium channels. Listen as these experts discuss the role of aldosterone and the mineralocorticoid receptor in ion channel expression in the vasculature, as well as future next steps related to sex differences and cell-specific knockout models.

 

Maloree Khan, Alex I. Meuth, Scott M. Brown, Bysani Chandrasekar, Douglas K. Bowles, and Shawn B. Bender Aldosterone impairs coronary adenosine-mediated vasodilation via reduced functional expression of Ca2+-activated K+ channels  Am J Physiol Heart Circ Physiol, published June 14, 2019. DOI: doi.org/10.1152/ajpheart.00081.2019

Total Sleep Deprivation and MSNA in Older Adults

Does 24 hours of total sleep deprivation affect older women and older men differently? Associate Editor Nisha Charkoudian (U.S. Army Research Institute for Environmental Medicine) interviews lead author Jason Carter (Michigan Technological University) and expert Nina Stachenfeld (Yale University School of Medicine) about the innovative study by Carter and co-authors, who found a sympatho-excitatory response to the sleep deprivation protocol in older women, but not in older men. The work by Carter et al suggests that the autonomic nervous system may have a larger role in older women who are sleep deprived, which is particularly important given that older women are at higher risk of developing hypertension than their age-matched male counterparts. Carter and colleagues conclude that "the association between sleep deprivation and hypertension is real." Will this new research kickstart a push for sleep as medicine for cardiometabolic diseases? Listen and find out.

 

Jason R. Carter, Ida T. Fonkoue, Ian M. Greenlund, Christopher E. Schwartz, Babak Mokhlesi, Carl A. Smoot Sympathetic Neural Responsiveness to Sleep Deprivation in Older Adults: Sex Differences Am J Physiol Heart Circ Physiol, published July 29, 2019. DOI: doi.org/10.1152/ajpheart.00232.2019

Heat Therapy vs. Exercise in Peripheral Arterial Disease

Can heat therapy improve exercise tolerance in peripheral arterial disease patients? Associate Editor Nisha Charkoudian (U.S. Army Research Institute of Environmental Medicine) interviews lead author Ashley Akerman (University of Ottawa) and content expert Zachary Schlader (Indiana University) about the novel passive heat training study by Akerman and co-authors. While exercise is the gold standard for conservative management of peripheral arterial disease (PAD), patients often struggle to comply with exercise treatment guidelines due to painful atherosclerotic plaque build-up in their arteries. Aimed at breaking the vicious cycle of needing to exercise but failing to do so because of pain, Akerman and collaborators designed a 12-week intervention study to compare exercise to heat therapy in older PAD patients. While functional walking improved for both groups, systolic blood pressure was markedly reduced in the heat therapy group. Surprisingly, other measures such as blood volume and flow mediated dilation were largely unchanged in both groups. Could these results have a wider impact on other patient populations, such as younger individuals recovering from an injury or diabetes patients?

 

Ashley P. Akerman, Kate N. Thomas, Andre M. van Rij, E. Dianne Body, Mesfer Alfadhel, James D. Cotter Heat therapy vs. supervised exercise therapy for peripheral arterial disease: a 12-wk randomized, controlled trial Am J Physiol Heart Circ Physiol, published June 5, 2019. DOI: doi.org/10.1152/ajpheart.00151.2019

Dietary Calanus Oil, Energy Metabolism, and Cardiac Function

How can a minute crustacean found in the Norwegian seas help to normalize cardiac metabolism in obese subjects? Associate Editor Fabio Recchia (Temple University and Scuola Superiore Sant'Anna) interviews first author Kirsten Jansen (UiT The Arctic University of Norway) and expert Luc Bertrand (Université Catholique de Louvain) about the innovative new study by Jansen and co-authors. Using a mouse model of high fat diet-induced obesity, Jansen and collaborators showed that 8 weeks of food supplementation with a small amount (just 2%) of dietary Calanus oil, which is derived from the marine zooplankton Calanus finmarchicus, improved cardiac function after 20 minutes of global ischemia. The unique fatty acid composition of the wax esters in Calanus oil is expected to activate GPR 120 (an omega-3 fatty acid receptor) in the gut, causing secretion of GLP-1 and release of insulin from pancreatic beta-cells. What is the link between Calanus oil and a decrease in intra-abdominal fat deposition, glucose metabolism recovery in the heart, and calcium handling? Listen now.

 

Kirsten Maria Jansen, Sonia Moreno, Pablo M. Garcia-Roves PhD, and Terje S. Larsen Dietary Calanus oil recovers metabolic flexibility and rescues post-ischemic cardiac function in obese female mice Am J Physiol Heart Circ Physiol, published May 24, 2019. DOI: doi.org/10.1152/ajpheart.00191.2019