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July 18, 2018

Extra Vinculin Keeps Heart Cells Shapely, Keeps Aging Hearts in Shape

Overexpression of the structural protein vinculin confers health benefits to fruit flies. In fruit flies bred to produce 50% more vinculin, cardiovascular health was improved and lifespans were extended. Metabolism was more efficient, too. This image shows the vinculin-overexpressing heart of a fruit fly at one week of adulthood with red stain showing the contractile part of the cells. [Ayla Sessions]

  • A structural protein called vinculin reinforces the heart’s extracellular scaffolding. It also helps the heart’s contractile proteins stay organized, so that heartbeats stay strong. But the reasons behind vinculin’s ability to provide these benefits remain poorly understood. To clarify vinculin’s role in heart health—and hopefully illuminate potential pharmaceutical interventions—scientists based at the University of California, San Diego, have studied the effects of elevated vinculin in a convenient model, the fruit fly. According to these scientists, when vinculin is overexpressed in fruit flies, life span is extended, quality of life is improved, and metabolism is more efficient.

    "You can imagine many people question why it is important to study the hearts of fruit flies," says Adam J. Engler, Ph.D., a bioengineer at UCSD. "But what we're finding is that improving the function of these 100 or so heart cells can have a big impact on the metabolism of the fly."

    By breeding flies with complementary genes, Dr. Engler and his colleagues created a genetic switch that turned on extra copies of the vinculin-coding gene. To ensure that only cardiomyocytes were producing the protein, the group used the same activation machinery as a heart development gene called "Tinman." Dr. Engler explains that gene got its name "because you couldn't have a heart without it."

    The results of this genetic work appeared July 17 in the journal APL Bioengineering, in an article titled, “Preserved cardiac function by vinculin enhances glucose oxidation and extends health- and life-span.”

    “Using the rapidly aging fly system, we found that cardiac-specific vinculin overexpression increases heart contractility, maximal cardiac mitochondrial respiration, and organismal fitness with age,” the article’s authors wrote. “Systemic metabolism also dramatically changed with age and vinculin overexpression.”

    While typical fruit flies live for roughly six weeks, flies that made more vinculin survived up to nine weeks. Additionally, flies with a vinculin boost were more active and able to climb the walls of their enclosures, a test of fruit fly athletic ability.

    "Their quality of life is a lot better, although, that can sometimes be hard to measure," Dr. Engler notes. "You can't simply put them on a treadmill and say, 'Go.'"

    Dr. Engler and his group were surprised at how much improving cardiac function also helped the flies maintain a healthier metabolism. To measure this improvement, researchers fed the flies a special form of glucose and detected how the flies modified and used the sugar.

    Flies with more vinculin broke down more glucose than their counterparts. The team concluded higher vinculin levels in the flies' hearts enabled other organs to efficiently get the nutrients they needed in the breakdown process.

    “This work,” the UCSD team concluded, “establishes a new link between the cardiac cytoskeleton and systemic glucose utilization and the protection of mitochondrial function from external stress.” The team hopes to one day see its work lead to pharmaceutical solutions for humans that boost vinculin expression.

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