Life in the Womb Can Program Future Heart Disease Interview with:

Professor Dino A. Giussani PhD ScD FRCOG Professor of Developmental Cardiovascular Physiology & Medicine Department of Physiology Development & Neuroscience University of Cambridge UK Director of Studies in Medicine College Lectureship in Medicine '1958' Gonville & Caius College

Prof. Giussani

Professor Dino A. Giussani PhD ScD FRCOG
Professor of Developmental Cardiovascular Physiology & Medicine
Department of Physiology Development & Neuroscience
University of Cambridge
Director of Studies in Medicine
College Lectureship in Medicine ‘1958’
Gonville & Caius College
UK What is the background for this study? What are the main findings?

Response: Heart disease kills 1 in 3 people worldwide.  When we hear about heart disease, the first thing we think of is a gene-environent interaction.  That is to say, how our genes interact with traditional lifestyle factors, such as smoking, obesity and/or a sedentary lifestyle to promote an increased risk of cardiovascular disease.  However,  it has also become established that the gene-environment interaction early in life may be just as, if not more, important in ‘programming’ future heart health and heart disease. That is to say, how the quality of the intrauterine environment in which we develop may also shape our future heart risk.  Evidence from human sibling-pair studies suggests that these relationships are causal, that they occur independently of genotype and that they are significantly influenced by the quality of the intrauterine environment during pregnancy.  For instance, bariatric surgery to decrease the weight of obese women reduced the risk of obesity, insulin resistance and raised blood pressure in children born after surgery compared to those born before. Therefore, these studies highlight a disproportionate risk of disease in offspring born from the same mother but under different in utero conditions, providing strong evidence in humans that the environment experienced during this critical period of development directly influences long-term cardiovascular health.

One of the most common outcomes of complicated pregnancy in humans is chronic fetal hypoxia, as can occur during placental insufficiency or preeclampsia.

The main findings of our study show that prenatal hypoxia can programme future heart disease in the offspring and that maternal treatment with the antioxidant vitamin C can be protective (see paper attached). What should readers take away from your report?

Response: Our discoveries highlight that when considering strategies to reduce the overall burden of heart disease, a much greater attention to prevention rather than treatment is required.  Readers should now appreciate that a component of heart disease in later life can be predetermined before birth by the quality of the pregnancy, rather than lifestyle factors such as smoking and obesity.  Secondly, that this can be prevented by treating as early as possible during the developmental trajectory, rather than waiting unit the disease process has become irreversible – if possible by ‘bringing preventative medicine back into the womb’ What recommendations do you have for future research as a result of this work?

Response: When working with animal models of cardiovascular dysfunction before birth, the temporal profile of cardiovascular development between species is a highly important consideration for successful interventional translation to the human clinical situation.  Rodents are altricial species, born highly premature, in which cardiovascular maturation continues past birth, becoming completed by the second week of postnatal life. In contrast, sheep and humans share similar prenatal tempos of cardiovascular development and some breeds of sheep, like Welsh Mountain, give birth primarily to singleton lambs of similar weight to term human babies.  Hence, sheep were specifically selected for this research to make the work to increase the human relevance and its clinical application.  The data show that only high doses of Vitamin C treatment in ovine hypoxic pregnancy were protective, incompatible with human treatment.  Therefore, there is an urgent need to screen alternative antioxidant therapy to identify potential candidates for human clinical translation. 


Intervention against hypertension in the next generation programmed by developmental hypoxia

Kirsty L. Brain Beth J. Allison, Youguo Niu, Christine M. Cross, Nozomi Itani, Andrew D. Kane, Emilio A. Herrera, Katie L. Skeffington, Kimberley J. Botting, Dino A. Giussani

PLOS Biology Published: January 22, 2019

Feb 7, 2019 @ 8:19 pm

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