Pinpointing Individual Susceptibility for Heart Disease

Pinpointing Individual Susceptibility for Heart Disease

March 29, 2015

Summary: Brian Bennett, PhD, with the UNC Nutrition Research Institute at the NC Research Campus in Kannapolis is developing new scientific approaches to uncover individual susceptibility to heart disease.

Eat a healthy and balanced diet. That is the first advice that people who need to reduce their risk for cardiovascular disease (CVD) receive.

But what if some nutrients in “healthy” foods interact with an individual’s genetic make-up in a way that actually increases their risk for CVD?


Brian Bennett, PhD

That is the question that Brian Bennett, PhD, is trying to answer. Bennett is an assistant professor of genetics, nutrition and heart disease with the UNC Chapel Hill Nutrition Research Institute (NRI) at the NC Research Campus (NCRC) in Kannapolis. He is pushing the boundaries of nutrigenomics, which is the study of how genes and diet interact, to reveal new clues about individual susceptibility for atherosclerosis and other forms of CVD.

In peer-reviewed journal articles published in the past year, Bennett pioneered findings on the connection of CVD and genetic-nutrient pathways, genes and gut microbiota. He has also established new research models for the study of nutrigenomics as it relates to heart disease.


Systems Genetics and Cardiovascular Disease

Bennett specifically studies atherosclerosis. More commonly known as hardening of the arteries. It is caused by plaque, which is made of cholesterol, fats, cellular waste, calcium and other substances, building up in the arteries as people age. The plaque restricts blood flow making the arteries less flexible, which raises the risk of heart attack, stroke and other forms of CVD.

In a journal article published in G3: Genes, Genomics and Genetics, Bennett worked with scientists at Jackson Laboratory, UNC Chapel Hill and the NRI to identify Apobec 1 on Chromosome 6 as a gene related to the development of atherosclerosis.  Apobec1 is an “editing enzyme” that regulates low-density lipoprotein (LDL), the “badcholesterol that contributes directly to atherosclerosis.

The buildup of plaque also creates inflammation in the arteries of the heart.  In a paper published in BMC Med Genomics, Bennett and his colleagues analyzed a pathway of genes that led to the identification of a gene called Cd44 as a “critical mediator of atherosclerosis.” The research showed that alterations in the expression of Cd44 “mediate inflammation” related to atherosclerosis “through a complex transcription network involving a number of previously uncharacterized genes.”

“Our systems genetics approach, which attempts to model the link between genetic differences and disease susceptibility, is a powerful approach to understand disease,” Bennett said. “We are building on our previous studies and now are focused on how these underlying genetic variations interact with dietary components to affect susceptibility to cardiovascular disease.”


Understanding Diet and Genetic Susceptibility

Bennett’s lab also studies specific gut microbiota and a metabolite (TMAO) related to “cardiometabolic health.” He determined that differences in the microbiota were maintained due to diet. This research established a model for further studies of gut- CVD connection. The results were published in the journal Mammalian Genome.

“A focus of my laboratory is to understand how differences in the bacteria that line our digestive tract affect susceptibility to cardiovascular disease.  This aspect of biology and its impact on human health has grown tremendously in the last few years,” Bennet explained.

In Bennett’s research, he employs a variety of in-bred and out-bred mouse models, computational analysis and cell culture. He takes advantage of the scientific expertise and instrumentation at the David H. Murdock Research Institute, which is located on the NCRC.

“I like to use newer more advanced mouse genetic approaches to look at how gene and diet interact to affect cardiovascular disease,” Bennett said. “The goal is to understand the genetics of heart disease and discover better and more effective therapeutic targets for CVD.

Learn more about the UNC Nutrition Research Institute. Visit the Bennett Lab website.

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