cardiometabolic – The Early Career Voice

Live Streaming Into Scientific Sessions 2018

December 12, 2018March 28, 2019 Trupti Shetty

AHA Scientific Sessions 2018 was a unique experience for me – unable to attend the meeting, I live-streamed the sessions (first time ever for a conference!). Two of my most favorite sessions this year were the panel discussion for advanced heart failure (HF) patients, “The Metabolic Face of Heart Failure,” and the mini-symposium on “Cutting Edge in Cardiovascular Science.”

One of the main highlights in the session Metabolic Face of HF, moderated by Dr Lynne Stevenson, was the talk by cardiovascular stalwart Dr. E. Braunwald, Brigham and Women’s Hospital. Dr. Braunwald spoke of the significance and latest practices in the use of Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors, a class of FDA-approved drugs for type-2 diabetes. He indicated how SGLT2 inhibitors should be explored beyond diabetes treatment and these class of drugs can benefit HF patients as well. “I had to learn about blood clotting 30 years ago, which was difficult,” he modestly admitted as he clarified the renal effects of SGLT2 inhibition. His views also seemed to resonate with Dr. Subodh Verma, St. Michael’s Hospital, Toronto and Dr. John McMurray, Glasglow University, as they covered SGLT2 inhibitors in HF, as well.

Other speakers at this session, Dr. Neha Pagidipati, Duke University and Dr. Lewandowski, Ohio State University, touched upon aspects of stroke and metabolism regulating HF, respectively. While Dr. Pagidipati compared the risk of cardiovascular diseases and stroke with the risks of diabetes, Dr. Lewandowski explained how metabolic regulator PPAR-a (transcriber of genes in fat metabolism) could be a player explored in targeted therapy.

The session ‘Cutting Edge in Cardiovascular Science’ had presenters covering diverse strategies in dealing with cardiovascular therapy, ranging from computational screening to identifying small molecule compounds, to decoding neurovascular networks and the gut microbiome. Dr. Stanley Hazen from Cleveland Clinic presented his work on understanding the microbes in the gut and their role in driving cardiovascular diseases. Dr. Hazen explained how food like red meat, which are rich in components like phosphatidyl serine, activates the gut microbiome. He described the significance of trimethylamine N-oxide (TMAO) pathway in liver and its association with HF, stroke and cardiovascular diseases. He also strategized the use of enzyme in TMAO pathway as targets of small molecule inhibitors.

Dr. Joseph Loscalzo, Brigham and Women’s Hospital, explained how repurposing drugs and finding drug targets computationally could help precision medicine vastly. He also offered his expertise and tools as open access to AHA members. Finally, Dr. Costantino Iadecola, Cornell, elaborated on the heart-brain connectome. He brought attention to the fact that dementia, known to cause hardening of arteries, led to Alzheimer’s, but we all forgot about the vascular complications of this. He bridged this connection between neurovascular dysfunction and cognitive impairment and went on to explain his research on the intake of high salt in diet caused dementia in mice models. To learn of such versatile range of topics in a session was illuminating, to say the least!

Researchers must spend time thinking about applications of their current projects beyond their own niche – this is the only way we can widen our horizons with existing tools.

Live Streaming, Cardiovascular Disease, and Violence: What I Learned at Scientific Sessions 2018

November 14, 2018March 28, 2019 Jacqueline Leachman

Take a trip back down memory lane to your glory days as a happy and shiny nine-year-old. If your childhood was as amazing as I remember mine to be, then you spent your days running outside with friends, making mud pies, and then fabricating methods by which you could trick your little sister into eating said mud pies. Now even though life is all spick-and-span for you at that age, imagine that you have a close friend whose parents are experiencing some domestic problems – so bad in fact, that it results in the mother attempting to commit suicide by ramming the car, full speed, into a cement block with your friend and his/her two other siblings inside. In your present day and age, can you even begin to fathom the degree of trauma that this past event brought to your friend? Now, would you believe me if I say that if undealt with, your friend may not only experience mental health issues but also cardiometabolic problems? While this may not be your first thought, it is now becoming more widely known that violence (or stress) is an independent risk factor for adverse cardiovascular health. This story may seem just a tad over the top; however, this was the topic of discussion for the session titled Unpacking the Cardiovascular Biology of Violence at Scientific Sessions 2018 and was the eye-opening account given by physician Marjorie Fujara from Chicago during her presentation.

As a new graduate student, this was my first time experiencing Scientific Sessions and I was completely taken aback by the various works discussed. Presentations that I was luckily able to witness via Live Streaming. Yes, you read correctly, LIVE STREAMING. Complete transparency here, I definitely opened my iPad with the preconceived notion that I would not be as engaged watching from my tiny screen in comparison to what I would experience being presented live and in-person. However, from the comforts of my own home, I found myself unreservedly hooked on the late-breaking science from researchers across the country. From the new Physical Activity Guidelines, to the nature versus nurture of cardiovascular disease, it was without a doubt an exciting weekend for science!

Considering the variety of disciplines at the conference, there were a number of ways to personally connect to the science presented. For example, my lab studies the effects of early life stress (or adverse childhood experiences) on the development of obesity and its related diseases later in life. As a result, the cardiovascular biology of violence talks were the ones that resonated with me the most because of its applications to my own research and personal interests.

During the discussion on the connections between heart health and trauma exposure, one panelist considered the case of primordial violence on developmental programming. Key points stemmed around the idea that excessive punishment led to increased levels of circulating cortisol. This then results in damage to the hippocampus (memory and learning), amygdala (emotions), and frontal cortex (reasoning). This data has led to the implementation of “No Hit Zones” in various hospitals. At the genetics level, however, what makes the people who experience increased levels of violence different from the rest of the population? When considering the epigenetics of the situation, violence in one’s life results in alterations in DNA methylation patterns (either hypo- or hyper-) and eventually leads to a higher cardio-metabolic risk. During the discussion, it was mentioned that for a child, just hearing about violence in one’s own community resulted in a difficulty concentrating for periods ranging from two days to an entire month. You can easily begin to wonder, “What does this mean for children living in areas with high homicide rates?” Overall, people exposed to trauma, and are not properly dealing with it, are predisposing themselves to diastolic elevations much earlier in life consequenting in early onset of cardiovascular disease.

The question is now, “What interventional methods can we use to better help people who are experiencing cardiac alterations due to increased stress exposure?” One solution discussed is the Bright Star Community Outreach program. Bright Star is a nonprofit aimed at using science and research to aid members of the south side Chicago community in recovering from the trauma of violence. By confronting the trauma, instead of bottling it away, they hope to help people to end the cycle and limit violence-induced early cardiovascular insults.

As the reader, and possibly someone who was unable to attend (or live stream) AHA Scientific Sessions 2018, what else do you think can be done clinically to better serve this group in terms of cardiovascular health? Do you think they will need different pharmacological interventions compared to the “traditional” hypertensive patient, for example?

Disclaimer

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of The American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately. ”

Gut Microbiota Modulation: From Bench to Bedside

August 13, 2018March 28, 2019 Shayan Mohammadmoradi

In a series of previous blog posts, I delved into the role of the gut microbiome and its contribution to cardiovascular health. As it is almost time to wrap up this year’s blogging series, I thought to provide some final points about this topic.

Large lines of evidence that shows gut microbiota is a major player in host metabolism homeostasis, has led to increased interests in leveraging findings for therapeutic aims in cardiometabolic complications. Here, I propose a framework for modulation of gut microbiota with therapeutic purposes (figure):

Schematic presentation of microbiota study frame-work. This simple representation suggests three major steps for conducting a microbiome study with the aim of investigating a disease phenotype and possible therapeutic outcome.

1. The first step would be characterizing the microbiome of disease phenotypes illustrating the alterations of specific bacterial taxa and metabolites.

2. Secondly, Koch’s postulation should be fulfilled. In short, the specific taxa should be found in abundance (or indicate specific ratio/levels) in the organism with disease phenotype but not in the healthy phenotype. Secondly, the responsible taxa (or the specific ratio/level of abundance) should be isolatable (or reproducible) and finally, transfer the disease-related taxa (or creating specific ratio/level responsible for disease) to the healthy host microbiome should introduce the disease.

3. After identifying the responsible bacteria or produced metabolites that fulfilled the Koch’s postulation, the third step would be designing an intervention based on the cardiometabolic complication, its progression level and personalization of intervention for each patient. Approaches to therapeutically modulate gut microbiota would be using probiotics, prebiotics, dietary constituents and drugging the microbiome for more specific targeting. Jamming microbiota communication, microbiome programming with modified smart bacteria and the introduction of RNA-guided nuclease CRISPR using bacteriophage carrier are among the new approaches that are starting to form for modulation of the gut microbial endocrine organ. Moreover, fecal microbiota transplantation (FMT) is also among the new approaches in treating metabolic anomalies and recently initiated clinical trial “Fecal microbiota transplant for obesity and metabolism” (ClinicalTrials.gov NCT02530385) is expected to show interesting results in the near future. Still, as mentioned throughout the series of blog posts, our understanding from complex interactions and functions of gut microbiome is in infancy and further animal and human studies are required to shed light on precise microbial targets and prevent the unforeseen consequences of long-term microbial disruption.

Conclusion and Closing Thoughts

Indeed, the community of bacteria residing in the human body was ignored for many years. But, recent evidence started to shape the idea that human’s microbial symbionts play multiple functional roles in maintaining normal metabolic functions. Successful improvement of metabolic syndrome and obesity that was discussed throughout these blog series indicate that future treatments may be, at least partially, based on microbiota interventions. More precise interventions should be developed to address the desired modulatory effect, yet, it raises new challenges since a major portion of gut bacteria is still uncultured. Also, regulatory aspects of current interventions including FMT, probiotics, prebiotics and bacterial metabolite inhibitors should be addressed in more detail since neither formulations development nor quality control guidelines are available. Moreover, it is time to move forward from small cross-sectional studies to more large-scale epidemiological investigations to understand better whether the microbial alterations cause disease development or the complications itself results in such alterations. In order to make the results of small and large microbial studies more clinically implantable, the field needs to generate universal standards for sample collection, data analysis, and sequencing to allow reproducibility and unbiased comparisons between different studies.

Despite all the hurdles in microbiome studies and translation of findings, there has been a bloom in researchers and companies looking for diagnostic and therapeutic strains and approaches to modulate them and track such modulations. The latter is more emphasized by the recent announcement from White House Office of Science and Technology Policy for the launch of United States National Microbiome Initiative (NMI) that aims to foster microbiome studies in different ecosystems. NMI aims to expand the microbiome workforce, develop platform technologies and support research to advance our understanding of microbiome and restoring its healthy function in different complications.

In the end, it is vivid that this novel area of research may impact medicine in the very near future and by addressing the current challenges, incorporated microbiome-based diagnostic and therapeutic protocols into patient care starts to emerge.

Shayan is a caffeine-dependent Ph.D. Candidate at the Saha Cardiovascular Research Center, University of Kentucky. His research area is focused on vascular biology and lipid metabolism. He tweets @MoradiShayan, blogs at shayanmoradi.com and he is the Winner of World’s Best Husband Award (Category: nagging).