When BRCA1 is deactivated, it can lead to hardening of the arteries, mouse study suggests
SUNDAY, Nov. 15 (HealthDay News) -- The over-activity of a gene known to boost a woman's risk for breast cancer may have a good side, making arteries healthier, a new study suggests.
The study, performed in mice, also found that when this gene, called BRCA1, is turned off, it promotes an inflammation that can lead to atherosclerosis or hardening of the arteries.
Although there has been no previous observation of increased cardiovascular death specifically in the large number of people who carry the BRCA1 mutation, there has been a surprising suggestion of higher non-cancer death in this population, noted study senior author Dr. Subodh Verma, who was to present the results Sunday at the annual meeting of the American Heart Association in Orlando, Fla.
The finding will "probably unleash a whole flurry of studies probing the databases and probing the populations that carry the BRCA mutations with respect to propensity for cardiovascular disease," said Verma, a cardiac surgeon at St. Michael's Hospital and associate professor of surgery at the University of Toronto in Ontario, Canada. "We were surprised at how [the gene] is a gatekeeper of not just cardiac survival but also vascular function in atherosclerosis."
Mutated forms of the BRCA1 and BRCA2 genes can each raise a woman's odds for breast and ovarian cancer risk at a younger age. When working right, the genes are tumor-suppressor genes and are key players in repairing DNA. When the genes are mutated, however, they can't repair DNA and unrepaired flaws can start a chain of events that ultimately leads to cancer.
"Things like tumor-suppression genes in this case may [also] have multiple effects that either promote, or, if they're abnormal, delay or limit the damage to arteries. That's what these researchers are hypothesizing," said Dr. Russell Luepker, an American Heart Association spokesman and Mayo professor at the School of Public Health of the University of Minnesota in Minneapolis. "They surmise from their research that the breast cancer-suppressor gene may very well be playing a role in controlling these lesions [inflammation] and if you don't have a normal BRCA gene, you may have more difficulty suppressing these lesions."
"If you have some abnormality in this gene, if you don't have a normal gene structure, then you're not able to suppress the formation of tumor cells," he added. "Some people have argued that atherosclerosis lesions in the arteries are really a cancer-like lesion because the tissue is abnormal and things organize and form in ways that in some ways are a bit like cancer."
The normal version of the BRCA1 gene can put a cap on cell inflammation as it relates to breast cancer.
But the question has been whether these anti-inflammatory properties extend to other parts of the body.
If plaque build-up in arteries from atherosclerosis get bad enough, bits of plaque can break off and block the vessel. If blood supply to the heart is cut off, it can result in a heart attack.
In this new study, an overactivated BRCA1 gene in lab mice produced a chemical that spurred the formation of new blood vessel proliferation. More and newer blood vessels mean better blood supply to areas of the body without good circulation, the researchers pointed out.
There was also less inflammation in these mice, compared to those with a lower-functioning BRCA1 gene, and fewer atherosclerotic lesions.
While confirmation in humans remains a long way off, the findings suggest that people with mutations in the BRCA1 gene may be predisposed to heart disease, experts said.
There's more on atherosclerosis at the American Heart Association.
SOURCE: Subodh Verma, M.D., Ph.D., cardiac surgeon, St. Michael's Hospital, associate professor of surgery, Canada Research Chair in atherosclerosis, University of Toronto, Canada; Russell Luepker, M.D., Mayo professor, School of Public Health, University of Minnesota, Minneapolis; Nov. 15, 2009, presentation, American Heart Association annual meeting, Orlando, Fla.
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