Grant: CIHR Fellowship

Cardiovascular disease (CVD) is the leading cause of death in Western countries, and is predicted to become the leading cause of death worldwide. Studies in the last 20 years have shown that adverse events during pregnancy can permanently affect the long-term health of a fetus. That is, someone exposed to stress during fetal life is at a greater risk of developing high blood pressure, stroke and heart attacks as adults. One of the most common complications in pregnancy is low oxygen supply to the fetus. We have shown that low oxygen supply to the fetus is linked to blood vessel damage in adults, although the exact causes are not known. This aim of this project is to identify the mechanisms by which low oxygen supply causes blood vessel dysfunction. The project focuses on endothelin (ET), which is an important player in various cardiovascular disorders. The project aims to determine if and how ET activity goes awry. To carry out these experiments, rats will be put in a chamber with low oxygen (12%) during the last trimester of pregnancy; these will be compared to rats that were kept at normal oxygen (21%) throughout pregnancy. Once the rats give birth, the offspring will be raised normally. When the rats become young adults (4 months), or aged adults (12 months),blood vessels will be removed from anesthetised animals, and will be mounted in a myograph system, in which we can assess vascular function. We will conduct experiments with various drugs to determine if ET, and other systems with which it interacts, are altered. Using treatments immediately after birth, we will also attempt to prevent the blood vessel damage from occurring. This work ultimately seeks to uncover events in very early life that increases one's risk CVD, thereby giving us information about early treatment options to prevent its eventual onset.