Haas and his team observed in an earlier study that when mice become obese, females grow lots of new blood vessels to supply the expanding fatty tissue with oxygen and nutrients, while males grow much less. In this latest study published in iScience, Haas and her co-authors, including York PhD student Alexandra Pislaru, Faculty of Health assistant professor Emilie Roudier and former York postdoctoral student Martina Rudnicki, focused on the differences in endothelial cells that make up the building blocks of these blood vessels in fatty tissue. The team used software to sift through thousands of genes to zero in on those thought to be associated with blood vessel growth. They found that processes associated with the proliferation of new blood vessels were elevated in female mice, while males had a high level of processes associated with inflammation.
“It was very striking to see the extent of inflammation-associated processes that were prevalent in men,” Haas recalls. “Other studies have shown that when endothelial cells have this type of inflammatory response, they are very dysfunctional and don’t respond properly to stimuli.” Pislaru, who works in Haas’ lab and is co-first author of the study, participated in this project as part of his thesis.
“It is exciting to observe the continued resilience that female endothelial cells display even when stressed by a long-term high-fat diet,” says Pislaru. “The results of our study may help researchers better understand why obesity manifests differently in men and women.” The researchers also looked at the behavior of endothelial cells when they were removed from the body and studied in petri dishes.
“Even when we take them out of the body where they don’t have circulating sex hormones or other types of factors, male and female endothelial cells still behave very differently from each other,” Haas explains. Female endothelial cells replicated faster, while male endothelial cells showed greater sensitivity to an inflammatory stimulus. By comparing with previously published datasets, the researchers found that endothelial cells from aged male mice also displayed a more inflammatory profile than female cells.
“You can’t assume that both genders are going to react the same way to the same series of events,” says Haas. “It’s not just an obesity problem – I think it’s a much broader conceptual problem that also encompasses healthy aging. One implication of our findings is that there will be situations where the ideal treatment for men will not be ideal for women and vice versa.” The study was funded by a grant from the Canadian Institutes of Health Research, as well as the Natural Sciences and Engineering Research Council of Canada and York Faculty of Health.
While humans and mice have different genes that can be turned on or off, Haas thinks the general findings would likely apply and is interested in studying the same cells in humans for future research. (ANI)
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