Tailoring health care to you
By Amanda Chase, PhD
October 6, 2020
Precision medicine is an exciting, emerging approach that considers an individual patient’s genes, lifestyle, and environment in disease treatment. In some ways, this concept has been part of healthcare for many years. For example, a blood transfusion is given when the donor’s blood type is matched to the recipient to reduce complications. More recently, new techniques and tools have opened the door for significant advances in the potential of precision medicine.
Targeted treatment is an intriguing step for precision medicine. Targeted treatment, which can also be called precision drugs, is the chance to provide effective (higher) drug concentrations at the specific areas in the body (tissues) that are diseased, while the rest of the body receives less or no drug. Something like targeted drug treatment could be groundbreaking for cardiovascular disease treatment. Cardiovascular disease is the number one cause of death in the US, according to the American Heart Association, with 1.5 million heart attacks per year that result in 500,000 deaths. If there was the ability to direct drugs at an effective concentration to the heart, it could result in optimized recovery and improved treatment.
A key to understanding and implementing precision drugs is in understanding what makes each tissue unique, or identifiable. In a recent paper in Circulation, a team of researchers from Stanford Cardiovascular Institute, led by first authors David Paik, PhD, Lei Tian, PhD, and Ian Williams, PhD, and senior author Joseph Wu, MD, PhD, looked at what made endothelial cells from different tissues unique. Endothelial cells (ECs) line blood vessels and help regulate blood flow, among many other important functions. If these ECs do not function correctly, it can lead to disease. For example, if ECs in the heart are damaged/diseased, it can lead to suboptimal repair of damaged heart tissue, such as after a heart attack. Importantly, there are differences in the ECs depending on the tissue they are found in. One could imagine ECs to be like tiles in your house: tiles have certain aspects that make them “tiles,” but the ones on the kitchen floor are different from those on the bathroom floor are different still from those that may be elsewhere in your house. There are reasons each tile is selected for a specific room, similar to how ECs have characteristics that place them in specific tissues. Understanding what those specific characteristics are for each tissue is a critical step in precision medicine and targeted therapy.
The Stanford Cardiovascular Institute team of researchers used novel techniques to look at markers, pathways, or other unique features of ECs in 12 different mouse organs, including the kidney, brain, heart, liver, lung, and pancreas, among others. They looked at all of the RNA transcripts in single cells, referred to as single-cell transcriptomics. By studying at the level of individual cells, they were able to look at a sub-group of cells that are specific for each tissue. Doing this, they identified signature markers that were enriched in ECs from different mouse tissues, and found that some of those markers are the same in ECs in the mouse and in humans. The markers, therefore, could be targets for tissue-specific drug delivery. Intriguingly, they also found some male and female tissue-specific gene expression, including in the heart. This could, in part, explain known sex differences in cardiovascular disease risks. They also opened the door for more information to be learned about aging or other disease conditions to continue to move forward the potential of precision medicine.
Other authors affiliated with the Stanford Cardiovascular Institute include Hao Zhang, Chun Liu, Ridhima Mishra, Sean Wu, and Kristy Red-Horse. Siyeon Rhee is also a Stanford affiliated author.