Mitochondrial therapy in complicated pregnancies lowers the chance of cardiovascular problems in the offspring, suggests new research led by Professor Dino Giussani, the 1958 College Lecturer in Medicine at Caius.

The findings, published today in the journal Science Advances, show babies that experience low oxygen levels in the womb due to pregnancy complications often go on to develop heart disease in adulthood. The study, using sheep, discovered that a specialised antioxidant called MitoQ can prevent heart disease at its very onset.

Genetics, and their interaction with lifestyle risk factors such as smoking and obesity, play a role in determining heart disease risk in adults. But there is also strong evidence that the environment experienced during sensitive periods of fetal development directly influences long-term cardiovascular health - a process known as ‘developmental programming.’

Low oxygen in the womb - known as chronic fetal hypoxia - is one of the most common complications in human pregnancy. In a process termed ‘oxidative stress,’ low oxygen to the developing fetus can cause damage to its heart and blood vessels. Fetal hypoxia can be diagnosed when a scan during pregnancy shows the baby is not growing properly.

Professor Dino Giussani, Professor at the University’s Department of Physiology, Development and Neuroscience, explained: “Many people may be predisposed to heart disease as adults because of the low level of oxygen they received in the womb. By providing a specific mitochondria-targeted antioxidant supplement to mothers whose pregnancy is complicated by fetal hypoxia, we can potentially prevent this.”

Chronic hypoxia is common to many complications of pregnancy. It can be caused by a number of conditions including pre-eclampsia, infection of the placenta, gestational diabetes or maternal obesity.

Oxidative stress largely originates in the mitochondria - the ‘batteries’ that power our cells -  where the processes of respiration and energy production occur. To target mitochondria the Cambridge team used MitoQ, a specialised molecule that in contrast to conventional antioxidants can penetrate the mitochondria and accumulates within it, where it works to reduce oxidative stress.

Having established the safety of the treatment, the researchers gave MitoQ to pregnant sheep under lower than normal oxygen conditions - sheep are animals whose cardiovascular development resembles that of a human baby more closely than laboratory rats and mice. They found that the mitochondria therapy protects against fetal growth restriction and high blood pressure in the offspring as adults. Using chicken embryos they also showed that MitoQ protects against mitochondria-derived oxidative stress.

This is the first time that MitoQ has been tested during sheep pregnancy and according to Professor James Leiper, Associate Medical Director at the British Heart Foundation, the findings reveal “a plausible way to reduce the future risk of high blood pressure and consequent heart disease in babies from complicated pregnancies”. He said, “Further research is now needed to translate these findings from animals to humans and identify the most effective time in development to give the MitoQ supplement to ‘at risk’ babies - whether that’s a particular point during pregnancy or soon after birth. Overcoming this next hurdle will enable it to be tested in clinical trials.”

This new research comes at an apt time; there are increasing calls within the public health community to change the focus of cardiovascular disease research from treatment to prevention. “If we want to reduce the prevalence of cardiovascular disease, we need to think of prevention rather than a cure. Applying this concept to pregnancy complications, we can bring preventative medicine all the way back into the womb - it’s treatment before birth. It completely changes our way of thinking about heart disease,” said Professor Giussani.

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This research was funded by The British Heart Foundation, and the programme of work was approved by the University of Cambridge Animal Welfare and Ethical Review Board.

Image credit: Miss Wen Tong and Dr Rana Mallah

Reference

Botting, K.J. et al: ‘Translatable mitochondria-targeted protection against programmed cardiovascular dysfunction.’ Science Advances, 19 August 2020. DOI:10.1126/sciadv.abb1929

‘Prevention of heart disease can start before birth’, University of Cambridge website.