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Developmental Programming of Cardiac Disease
by Hypoxia

Researchers:  Kerri Smith, Hayat Baba and Zarin Gias

Developmental programming

An unborn baby requires a constant supply of oxygen to survive.  Complications during pregnancy, such as maternal smoking or placental infection, can limit the amount of oxygen the baby receives.  This condition, known as prenatal hypoxia, can seriously harm fetal heart development and increase the likelihood that the child will develop heart disease later in life.  We study the biological processes in the heart that are altered by prenatal hypoxia and we are developing maternal antioxidant therapeutics to prevent the negative effects and protect babies from high-risk pregnancies.

What is Developmental Programming of Cardiovascular Disease?

Developmental programming
  • It is well-established that genetics and lifestyle factors play a major role in cardiovascular disease.

  • However, cardiovascular disease can also be driven by exposure to environmental stress

  • We are very sensitive to environmental stress during fetal development; any kind of changes inside the womb can permanently affect the structure and function of our heart.

  • For example:  In the 1980s, an epidemiologist called David Barker discovered that babies born from mothers who were experiencing famine were  much more likely to be born small, and develop heart disease later in life.

  • This led to the "Barker's hypothesis" which states that environmental stress during fetal development can "programme" cardiovascular disease in adulthood. 

  • This phenomenon is now known as "developmental programming of cardiovascular disease".   

What is fetal hypoxia and how does it affect the heart?

  • Fetal hypoxia is a condition during pregnancy where oxygen supply to the fetus is reduced

  • It can result from pregnancies at high altitude, maternal smoking, preeclampsia and placental insufficiency

  • The fetus initially responds to hypoxia by preferentially distributing blood flow to vital organs, such as the heart and brain (brain-sparing response).

  • Although protective in the short-term, this strategy eventually leads to increased peripheral resistance, ventricular remodelling and cardiac dysfunction.

brain sparing
  • Importantly, offspring from hypoxic pregnancies continue to display cardiac abnormalities in adulthood, including diastolic dysfunction, sympathetic dominance and ventricular remodelling. 

  • This phenotype is reminiscent of early stage heart failure, and is thought to sensitise the cardiovascular system to disease.

Programming Projects in the Lab


Andy Trafford
Luigi Venetucci
Dino Giussani
Mike Murphy

Prof. Andy Trafford
Uni Manchester

Dr Luigi Venetucci
Uni Manchester

Prof Dino Giussani
Uni Cambridge

Prof Mike Murphy
Uni Cambridge

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