New imaging system reveals how female and male hearts respond differently to stress hormones

New research published in scientific progress It shows that female and male hearts respond differently to the stress hormone noradrenaline. Studies in mice may have implications for human heart disease, such as arrhythmias and heart failure, as well as responses to drugs by gender.

The team has built a new type of fluorescence imaging system that can use light to see in real time how the mouse heart responds to hormones and neurotransmitters. Mice were exposed to noradrenaline, also known as norepinephrine. Noradrenaline is a neurotransmitter and hormone associated with the body’s “fight or flight” response.

The results reveal that the hearts of male and female mice initially respond uniformly after exposure to noradrenaline. However, some areas of the female heart return to normal more quickly than the male heart, which makes a difference in the heart’s electrical activity.

The difference in electrical activity we observed is called repolarization in the female heart. Repolarization refers to how the heart resets with each beat and is closely related to certain types of arrhythmias. ”

Jessica L. Caldwell, lead author of the study

Caldwell is a postdoctoral fellow at the UC Davis School of Medicine Department of Pharmacology.

“We know that there are gender differences in the risk of certain types of arrhythmias, and this study reveals new factors that may contribute to different arrhythmia susceptibility between men and women,” Caldwell said. said.

Heart disease is the leading cause of death in the United States

Heart disease is the leading cause of death for both men and women in the United States. accounted for one in about four male deaths, 1 1 in 5 women will die in 2020. Despite the effects on both sexes, cardiology research is predominantly conducted on men.

In this study, researchers were interested in examining factors that may contribute to arrhythmia. They affect anywhere between her 1.5% and 5% of the population.

method

This new imaging system uses mice, called CAMPER mice, that have been genetically engineered to emit light during highly specific chemical reactions within the heart. cAMP binding.

The cAMP molecule (an abbreviation for cyclic adenosine 3′,5;-monophosphate) is an intermediate messenger that converts signals from hormones and neurotransmitters, including noradrenaline, into actions from cardiac cells.

Optical signals from CAMPER mice are transmitted by a biosensor that uses fluorescence resonance energy transfer (FRET). This FRET signal can be picked up at high speed and resolution by a new imaging system designed specifically for the heart. This allows researchers to record the heart’s response to noradrenaline in real time, along with changes in electrical activity.

This new imaging technique revealed differences in cAMP degradation and associated electrical activity in female and male mice.

Including female mice leads to discovery

According to the study’s senior author, Crystal M. Ripplinger, the researchers did not plan to study gender-based responses. But researchers began to see different patterns of responses and realized that the differences were based on gender.

Ripplinger is an electrical and biomedical engineer and professor of pharmacology.

When she started her lab at the UC Davis School of Medicine over a decade ago, she worked exclusively with male animals. That was the standard for most research at the time. But a few years ago, she began including male and female animals in her research.

“Sometimes the data for the two sexes are the same. “We’re discovering clues to differences we never suspected. We’re starting to realize that you can’t infer both sexes by studying one alone,” Ripplinger said.

She says it’s not clear from current research what the difference between cAMP and electrical activity means.

“The responses of female mice may or may not be protective. However, it is important to simply document measurable differences in responses to stress hormones.” I hope to learn

Other authors of this study include I-Ju (Eric) Lee, Lena Ngo, Lianguo Wang, Donald M. Bers, Manuel F. Navedo, and Julie Bossuyt from UC Davis. Sherif Bahriz of the University of California, Davis and the University of Mansoura. Bing (Rita) Xu and Yang K. Xiang are from UC Davis and her VA Northern California.

This work was supported by grants from the National Institutes of Health, the American Heart Association, and the Veterans Administration Merit Grant.