Skip to main content
Premium Trial:

Request an Annual Quote

NY Team Identifies Point Mutation That May Aggravate -- and Prevent -- Heart Disease

Premium

A team of researchers from Rockefeller University believes that a certain genetic pathway known to contribute to inflammation in coronary vasculature — and thus to myocardial infarction — may protect against the same condition.

The researchers focused on the Nuclear Factor Kappa-B, or NFkB, pathway and had originally set out to identify mechanisms of cardiovascular disease that were not related to one of the primary risk factors for the disease — namely, levels of HDL and LSL cholesterol.

“Having high cholesterol increases your risk, but does not mean that you will get heart disease,” lead author Susanne Idel wrote in her team’s paper, which appears in the Nov. 25 issue of Proceedings of the National Academy of Sciences. “So, there must be genetic pathways other than those connected to cholesterol metabolism.”

“Our research has identified a non-cholesterol related gene that is linked to the development of heart disease in mice,” she wrote. “In the long term, our hope is that we will have a more complex understanding of the genetics involved that gives us new tools for treating heart disease.”

To arrive at their results, Idel and her colleagues focused on the NFkB inflammatory response protein and the A20 gene that regulates it in mice. Though NFkB is activated in response to atherosclerotic plaques, the inflammatory response is not exclusive to them. Rather, the inflammatory cascade is “generally activated” when tissue is “damaged” by agents such as viruses, bacteria, chemicals, or physical trauma.

It is in response to this inflammation that the vascular and arterial intima react in ways associated with inflammation.

(The mechanism of NFkB regulation by A20 is not related to any of the known cholesterol pathways, the authors stressed.)

Because the NFkB pathway up-regulates inflammatory genes, and the subsequent inflammation is associated with atherosclerosis, “some scientists have focused on this pathway as one route” that promotes cardiovascular disease. “But mounting evidence suggests that the reverse may be true,” the team wrote. “Several research groups have created mice in which the pathway has been disabled and the animals’ blood vessels and arteries have actually less atherosclerosis.”

“The idea that NFkB has an anti-atherosclerotic effect is controversial,” Idel said in a statement issued by Rockefeller University. “But, if it were true that the pathway had only harmful effects, then turning it off should have protected the mice. This is not what we have observed. NFkB does turn on inflammatory genes, but you can’t disregard that it also turns on other genes that may be important for cell survival.”

For example, she added, NFkB regulates genes that promote anti-inflammatory and anti-apoptotic mechanisms. These other genes may play crucial roles, important, so it “might be beneficial” that the NFkB pathway remains active.”

The team identified A20 as a candidate gene for the “athero-related” study because it is within the locus of interest — chromosome 10. They also chose it because it regulates NFkB, and that its basic structure in the athero-protected mice differs slightly from the A20 in the athero-prone mice. The two versions differ by a single point mutation, the team said.

“The NFkB pathway turns on some genes that would be expected to ameliorate atherosclerosis and some genes that make it worse,” Idel said. “In the mice, an active pathway seems to be preferable, but more research is required to determine how the effects balance out.

“There is still much that is unknown about the genetics of heart disease, but A20 and the NFkB pathway offer promising leads worthy of more study,” the researcher said.

— KL

Filed under

The Scan

Just Breathing

A new analysis suggests that most Mycobacterium tuberculosis is spread by aerosols from breathing, rather than by coughing, the New York Times reports.

Just Like This One

NPR reports that the World Health Organization has hired a South African biotech company to recreate mRNA vaccine for SARS-CoV-2 that is similar to the one developed by Moderna.

Slow Start

The Wall Street Journal reports that Biogen's Alzheimer's disease treatment had revenues for July through September that totaled $300,000.

Genome Research Papers on Cancer Chromatin, Splicing in the Thymus, Circular RNAs in Cancer

In Genome Research this week: analysis of bivalent chromatin sites, RBFOX splicing factors' role in thymic epithelial cells, and more.