One new research published year scientific advance showed that women’s and men’s hearts respond differently to the stress hormone noradrenaline. The mouse study could have implications for human heart disorders such as arrhythmias and heart failure, as well as how different genders respond to drugs.
The team built a new type fluorescence image the system allows them to use light to see how the mouse works the heart reacts to hormones and neurotransmitters in real time. The mouse exposure to noradrenaline, also known as norepinephrine. Noradrenaline is both a neurotransmitter and a hormone involved in the body’s “fight or flight” response.
The results showed that the hearts of male and female rats responded uniformly initially after exposure to noradrenaline. However, some areas of a woman’s heart return to normal more quickly than a man’s heart, which makes a difference in how the heart works. electrical activity.
“The difference in electrical activity that we observed is called repolarization in women’s hearts,” said Jessica L. Caldwell, first author of the study. between each heartbeat and is strongly associated with several types of arrhythmias”. Caldwell is a postdoctoral scholar in the Department of Pharmacy at UC Davis School of Medicine.
“We know that there are sex differences in the risk of certain types of arrhythmias,” Caldwell said. “The study suggests a new factor may contribute to different susceptibility between men,” Caldwell said. gender and women”.
Heart disease is the leading cause of death in the US
Heart disease is the leading cause of death for both man and women in U.S.A. It accounts for about 1 in 4 deaths in men and first 1 in 5 women die in 2020. Despite the impact for both sexes, cardiovascular research is largely performed on male subjects.
In this study, the researchers were interested in looking at factors that could contribute to arrhythmias. Arrhythmia is a type of heart disorder in which the electrical impulses heart rate control not working properly. They affect somewhere between 1.5% to 5% population.
The new imaging system uses a mouse, called a CAMPER mouse, that has been genetically engineered to emit light in a very specific chemical reaction in the heart—cAMP binding.
The molecule cAMP (short for cyclic adenosine 3′,5;-monophosphate) is a messenger that converts signals from hormones and neurotransmitters, including noradrenaline, into action from heart cells.
The light signals from the CAMPER mouse are transmitted by a biosensor using fluorescence resonance energy conversion (CONSUFUSED). This FRET signal can be captured at high speed and high resolution using a new imaging system specifically designed for the heart. This allowed the researchers to record the heart’s response to noradrenaline in real time, along with changes in electrical activity.
This new imaging method reveals differences in cAMP degradation in female and male mice and those associated with electrical activity.
Including female mice leads to discovery
According to Crystal M. Ripplinger, the study’s lead author, the researchers did not plan to study responses based on gender. But the researchers began to see a different pattern of responses, leading them to recognize differences based on gender.
Ripplinger, an electrical and biomedical engineer, is a professor in the Department of Pharmacy.
When she started her lab at UC Davis School of Medicine more than a decade ago, she used only male animals. That was the norm for most studies at the time. But a few years ago, she started including both male and female animals in her research.
“Sometimes the data between the sexes is the same. But if the data starts to show differences, the first thing we do is look at gender difference. Using both male and female mice revealed clues to differences that we would never have suspected. Researchers are realizing that you can’t extrapolate to both sexes by studying only one sex,” says Ripplinger.
She notes that with the current study, it’s not clear what the difference in cAMP and electrical activity might mean.
“The response in female rats may or may not be protective. But simply documenting evidence that there is a measurable difference in response to stress hormones is crucial. We hope to learn more in future studies,” Ripplinger said.
Other authors on the study include I-Ju (Eric) Lee, Lena Ngo, Lianguo Wang, Donald M. Bers, Manuel F. Navedo and Julie Bossuyt from UC Davis; Sherif Bahriz from UC Davis and the University of Mansoura; Bing (Rita) Xu and Yang K. Xiang from UC Davis and VA Northern California.
Jessica L. Caldwell et al., Whole-heart multiparametric optical imaging reveals sex-dependent heterogeneity in cAMP signaling and repolarization kinetics, scientific advance (2023). DOI: 10.1126/sciadv.add5799
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