Recent Development and Advances in Basic Cardiovascular Science Research at AHA19

This year’s #AHA19 meeting, despite its abbreviated 3-day format, delivered a fantastic lineup of basic science research sessions, comprising of presentations from trainees to early career and senior investigators. Here I review some of the major topics in basic science cardiovascular research highlighted at #AHA19! This is by no means a comprehensive list of all exciting new developments in basic science, but what caught my attention the most.

Single-cell sequencing

Advances in single-cell RNA sequencing (scRNA-seq) technologies in the past 3-4 years have had a transformative effect on biomedical research, enabling the profiling and analysis of the transcriptomes of single cells at unprecedented resolution and throughput. scRNA-seq has allowed identification of novel or rare cell types, analysis of single-cell trajectory construction and stem or progenitor cell differentiation, and comparison of healthy and disease-related tissues at single-cell resolution. These applications have likewise been critical in advances in cardiovascular research, as evidenced by the generation of cell atlases of mammalian heart and blood vessels, elucidation of cardiovascular development and stem or progenitor cell differentiation mechanisms, and comparison of healthy and disease conditions for the development of novel therapeutic solutions.

#AHA19 highlighted the use of scRNA-seq in a truly wide gamut of applications, from cardiac development to cardiovascular tissue atlas to understanding disease mechanisms at the single-cell level. On Saturday Dr. Eric Olson opened his “Science Catalyst Keynote” by discussing scRNA-seq data of neonatal mouse cardiac regeneration, where his team identified intercellular crosstalk among various cell types and revealed the role of cardiac macrophage-specific Ccl24 in cardiomyocyte proliferation. In “Arrhythmia Research Summit: New Arrhythmia Concepts” session, Nathan Tucker from Massachusetts General Hospital showed his single-nuclei RNA-seq data of the four chambers of the human heart. During the “Abstract Rapid Fire Oral” sessions in Zone 1, Yifei Miao at Stanford University showed scRNA-seq data of human cardiac tissue with hypoplastic left heart syndrome.

On Sunday, during the “Mom, Where Do Baby Cardiac Myocytes Come From?” session, Fabienne Lescroart at Universite Libre de Bruxelles and Enzo Porrello at the University of Queensland displayed the use of scRNA-seq and lineage-tracing models to better understand cardiomyocyte division and proliferation during cardiac development in various model organisms. During the “Main Session”, Kory Lavine at Washington University School of Medicine discussed his scRNA-seq data that elucidated the cellular and molecular events of cardiovascular inflammation. Furthermore, the newly added “Single-Cell RNA Sequencing Bootcamp”, led by Jennie Lin and Nathan Tucker, was a major success with an enormous number of attendees. It was clear that such bootcamp events should be employed at other AHA subspecialty conferences, perhaps with a larger room and a longer session period to accommodate the full coverage of essential topics in the ever-evolving single-cell sequencing technology today. In the “Frontiers in Cardiovascular Target Discovery”, I myself shared unpublished data from our laboratory at Stanford Cardiovascular Institute in identifying organ-specific transcriptomic features of endothelial cells from the Tabula Muris dataset.

On Monday, the increasing use of single-cell sequencing in clinical and preclinical studies was evident. Anne Cornelissen from CVPath Institute discussed single-cell heterogeneity of endothelial cells post balloon angioplasty and stent implantation, and Man Rao from Fuwai Hospital in Bejiing, China showed scRNA-seq data in dissecting the cell type-specific molecular changes in heart failure.

Consequently, single-cell sequencing, in particularly those enabled by the microdroplet-based method, has become an essential tool in understanding cardiovascular biology. In addition to the heavy use of scRNA-seq, single-cell ATAC-seq is poised to become an important tool in deciphering the chromatin accessibility at the single-cell level, and spatial transcriptomic techniques for tissue- and location-specific investigation of gene expression.

A number of limitations of the technology does indeed exist, and I will discuss these in a later post. Stay tuned!

Omics

The “Omics Approaches in Cardiovascular Medicine” session on Sunday highlighted the role of multi-omics tools in basic and clinical cardiovascular research. Moderated by Sarah Franklin and Maggie Lam, the full spectrum of omics were discussed by the leaders in the field, including but not limited to: proteomics, metabolomics, epigenomics, “N of 1” personal omics, and machine learning.

With the continued efforts of the Trans-Omics for Precision Medicine (TOPMed) Initiative by the NIH NHLBI now entering Year 6, comprehensive integration and development of multi-omics tools will certainly be critical not only for advancing basic science but also in precision cardiovascular medicine.

Cardio-Oncology

Another big topic of the #AHA19 sessions was the rapidly rising field of cardio-oncology. What is cardio-oncology? I will have a blog post later dedicated to this subject. #AHA19 did a wonderful job of organizing a number of superb talks and poster presentations, from both the bench and the bedside. Some of the notable sessions included: “Cardio-Oncology or Onco-Cardiology: Cardiac and Cancer Treatment in the Balance”, “Novel Concepts in Cardio-Oncology”, and “Cardio-Oncology Debates” held on Monday.

In summary, the #AHA19, to me, was one of the most EXCITING sessions in recent years, which showcased the emergence and applications of new technologies used to address the new and old questions in cardiovascular research. The conference displayed innovative and insightful research from all over the world and from scientists in all career stages and diversity backgrounds, which may not have been the case for a few of the past sessions and thus should be highly lauded. Personally, I did wish that the conference was a bit longer (e.g. 3.5-day or 4-day instead of 3), as I found numerous interesting talks occurring concurrently. In particular, a majority of basic science talks were jam-packed into Sunday, calling for #AHA20’s extra efforts to spread the BCVS talks out across the three days of the sessions.

In any case, #AHA19 in my opinion was an IMMENSE success. Philadelphia was a wonderful (first-time!) venue for the sessions. All credit goes to the organizers of #AHA19, Dr. Bob Harrington, and the BCVS Council led by this year’s Chair Dr. Joseph Wu and Vice Chair Dr. Elizabeth McNally. I cannot wait to come back for #AHA20!

 

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