David L. Mattson, Ph.D.
Mechanisms of Hypertension
Around one out of three Georgians suffers from hypertension, or high blood pressure. That’s 2 million of our state’s citizens who are at higher risk of heart attacks and strokes. Renowned researcher David Mattson has devoted his career to investigating the underlying causes of hypertension and discovering new approaches to treatment.
The Mattson lab is particularly focused on salt-sensitive hypertension, high blood pressure that is worsened by a high-sodium diet. While not everyone with high blood pressure is sensitive to salt, doctors estimate that as many as two thirds of patients are — which means they’re much more likely to suffer from cardiovascular diseases like heart attacks and strokes, as well as organ damage like kidney failure.
To illustrate the potential harm of salt-sensitive hypertension, Mattson points to one major study that tracked its participants over 30 years. At the end of the study, 90 percent of the patients with normal blood pressure were still alive, but only 60 percent of those with salt-sensitive hypertension had survived. It’s clear that improving treatment options for salt-sensitive hypertension would deliver huge benefits for public health and extend the lives of many.
Mattson and his team investigate salt-sensitive hypertension mostly by observing the disease in rats. The team explores how salt-sensitive hypertension activates the immune system, causing inflammation and worsening the disease. They’ve analyzed how environmentally driven changes to DNA can contribute to the illness. And they’ve linked high blood pressure to changes in gut bacteria.
One of Mattson’s biggest findings came about through fortunate happenstance. The lab had been spending a lot of money on rat chow; for budgetary reasons, they decided to switch to a new and cheaper supplier. The cheaper rat chow was formulated with the same nutritional components — protein, carbohydrates and most importantly, the same quantity of sodium. But to Mattson’s surprise, the rats who were fed the new diet began to recover from their salt-sensitive hypertension.
The major difference in the food? A switch from animal-based to plant-based proteins.
Building on this finding, Mattson and his colleagues discovered that the healthy rats’ gut bacteria differed a lot from the rats with high blood pressure. Even more interestingly, they found that when they transferred the sick rats’ gut bacteria to the healthy rats, the healthy rats began to suffer from high blood pressure, too.
Finally, Mattson’s lab discovered that these changes in diet were linked to changes in how the rats’ genetic make-up affected their symptoms, through a process called epigenetic modification. While genes in both rats and humans are unchanging – you keep the genes you’re born with – the genes that take precedence and determine your health can change, depending on lifestyle factors like stress, pollution, exercise or in this case, diet.
So, while both the sick and healthy rats were genetically predisposed to salt-sensitive hypertension, those genes were only “turned on” in the sick rats. They then began producing more immune cells than needed, which increased inflammation and worsened their high blood pressure. When the rats began eating a new plant-based diet, those genes responsible for producing immune cells “turned off,” and the rats’ blood pressure improved.
Mattson is working to figure out why, exactly, the alternate, plant-based diet affected the rats that way. He hopes this work could point the way to an easy-to-take supplement that could help people with high blood pressure experience the same improvement, potentially with fewer side effects than conventional medicines.
Another promising avenue for Mattson’s research is anti-inflammatory drugs. His findings suggest that when changes to genetic expression trigger the immune system to make unnecessary immune cells, inflammation occurs and salt-sensitive hypertension worsens. Perhaps this could be treated with the same type of anti-inflammatory drugs that help patients with auto-immune diseases such as rheumatoid arthritis.
While Mattson’s lab primarily works with rats, they also collaborate often with clinical investigators to explore how their findings apply to human patients. For example, they’ve learned a lot from studies with human twins.
Because identical twins share identical genes, studying them helps researchers better understand which part of health is determined by genes, and which part is determined by lifestyle. Just as two rats with the same genetic predisposition for high blood pressure may have different health outcomes (depending on their diets), the same is true for identical twins.
In working with clinical researchers, Mattson is finding that the same epigenetic modification and gut bacteria changes that are linked to high blood pressure in rats are also present in human patients.
Mattson’s lab also looks at the impact of maternal diets on hypertension. Their research suggests that when a pregnant mom consumes a heart-healthy, low-sodium diet, it improves the future health prospects of her offspring. With support from GRA, his lab is expanding its technical capabilities, adding state-of-the-art equipment to better monitor the rats’ prenatal and fetal health.
- The role of the kidneys in hypertension
- Epigenetic modifications of the immune system in salt-sensitive hypertension
- Role of immune system on salt-sensitive hypertension
- Maternal dietary salt intake and its effect on hypertension
Straight from the Scholar
“We come in to work each day feeling energized and feeling like we can actually make a difference, and the resources made available through Augusta and GRA are enabling that. It’s a very exciting time. And with many colleagues here in the basic sciences as well as some wonderful clinical researchers who have access to individuals with salt-sensitive hypertension, we have the opportunity to further transfer our work to the human population.”