Professor Zhang's research group has been studying the effect of adverse intrauterine environment on fetal heart development and its lifelong pathophysiological consequences in the adult heart. Using an animal model of the pregnant rat, they found that fetal exposure to cocaine during gestation resulted in an increase in heart susceptibility to ischaemia and reperfusion injury in late adult life. Interestingly, the effect of prenatal cocaine exposure on cardiac vulnerability in adult offspring is gender-dependent, with the male heart being more susceptible to increased ischaemia/reperfusion injury induced by prenatal cocaine exposure.
Earlier work by professor Zhang's group showed that fetal chronic hypoxia also increased cardiac vulnerability to ischaemia and reperfusion injury in late adult life.
Epidemiological studies in humans have shown an association of fetal undernutrition in the womb and an increased risk of hypertension and ischaemic heart disease in adulthood. In addition to undernutrition as originally proposed, professor Zhang's studies suggest that other adverse factors such as cocaine abuse and hypoxia during gestation also cause fetal programming in utero, which has lasting and lifelong effects on the cardiovascular system in later adult life.
Acute ischaemic injury and myocardial infarction resulting from coronary artery disease is the major cause of death among people in the western world. Despite years of research, the causes for ischaemic heart disease are incompletely understood. The new studies from Professor Zhang's research group at Loma Linda University provide clear evidence in an animal model for the first time that ischaemic heart disease in adulthood can originate through fetal programming under an adverse intrauterine environment.
The findings are important because they provide novel insights that improve our understanding of risk factors for cardiovascular diseases including ischaemic heart disease, and link prenatal cocaine exposure and fetal hypoxia to their lifelong pathophysiological consequences in the adult heart. Because cocaine abuse and hypoxia are common problems in fetal development, these findings have obvious clinical significance.
The next step is to investigate the epigenetic mechanisms involved in fetal programming caused by adverse intrauterine environment, which is essential for explaining many fundamental biological processes by which a variety of cardiovascular dysfunctions and diseases emerge and evolve.
Notes to editors:
1. To view the full article, Prenatal cocaine exposure increases heart susceptibility to ischemia/reperfusion injury in adult male but not female rats. Soochan Bae, Raymond D. Gilbert, Charles A. Ducsay, Lubo Zhang, Journal of Physiology pg. 149, please go to www.blackwell-synergy.com, click on the Register button to receive a username and password and then login. (If you have already registered with Synergy, login with your user name and password.) Now, go to the My Synergy area and click on the Access tab. Now enter the following Access Token exactly how it appears here in the field provided: TJP May 2005. When your Access Token has been accepted you need to click on the Article tab to view the articles for 30 days. The next time you want to view the article, login at www.blackwell-synergy.com on click on the My Synergy tab and the article will be listed.
2. For further information contact: Soochan Bae, Raymond D. Gilbert, Charles A. Ducsay, Lubo Zhang at the Center for Perinatal Biology, Loma Linda University, School of Medicine, Loma Linda, CA 92350
3. The Journal of Physiology is owned and edited by the Physiological Society, published by Blackwell Publishing and available online at HighWire Press and Blackwell Synergy. Contents lists are available at www.jphysiol.org and www.blackwell-synergy.com.
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The Journal of Physiology