Diabetic mothers passing on more than just genetic characteristics to their children

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By Ciara Parsons, BA'15

With 50,000 new cases of heart failure diagnosed each year in Canada, heart disease serves as the second leading cause of death throughout the nation. Though various medications and surgical and biomedical device therapies can aid in the treatment of heart failure, the damage caused by heart disease is irreversible.

Looking to aid in the development of new therapies for heart failure is Dr. Qingping Feng, a professor in the Department of Physiology and Pharmacology at Schulich Medicine & Dentistry.

Through analyzing the pathophysiological mechanisms of heart failure and the molecular mechanisms involved, Dr. Feng aims to identify specific targets to hone in on and study further.

“In my lab, we have been studying the role of nitric oxide in heart development and the promotion of epithelial-mesenchymal transition. The hope is that we can identify which molecules promote cardiac repair and cardiac function. If a specific molecule can be identified, it can potentially be targeted as a treatment for heart failure,” said Dr. Feng.

Trained as a medical doctor, Dr. Feng began his career in China as a cardiologist. Struck by how little could be done for those suffering from heart failure and various maladies of the heart, he looked to research to try and uncover new remedies.

“As a physician, I would see my patients suffering and for a lot them there were very limited drugs and tools available for treatment. Besides my general fascination with the heart, this is a factor in why I became quite interested in cardiac research and the idea of possibly developing new therapies for heart failure,” he said.

Currently, Dr. Feng is analyzing the role of embryonic heart development in relation to congenital heart failure as a means of understanding how these early stages of human development contribute to long-term health complications.

“We have discovered that when you don’t have enough nitric oxide, the heart doesn’t develop as it should,” said Dr. Feng.

Using mice models as testing subjects, Dr. Feng has found that mice deficient in nitric oxide develop congenital heart defects similar to those experienced by humans, such as congenital atrial septal defect, ventral septal defect and valve defects.

“More recently, we showed that mice also develop coronary artery defects, like hypoplastic coronary artery disease, when deficient of nitric oxide,” said Dr. Feng. “If the malformation is mild enough in those affected, they can survive to adulthood. But when they do intense physical activities, their oxygen supply doesn’t meet their oxygen demand, which then triggers a heart attack and can cause sudden cardiac death.”

This severe, yet rare defect is often to blame when analyzing the number of children and adolescents who suddenly die of heart attacks after engaging in strenuous physical activity.

While it is widely known those with diabetes have a proportionally higher risk of developing heart failure, Dr. Feng has discovered that diabetic mothers also have a greater risk of bearing children with heart abnormalities.

“When women with diabetes have children, if the diabetes is not well-controlled, it poses a problem to both the mother and her baby. High glucose levels are considered to be teratogenic to embryos since it causes malformation,” he said.

Dr. Feng says his research has shown that reducing oxidative stress in diabetic mothers has proven to be an effective method of preventing the development of congenital heart defects in babies. He is also evaluating ways to increase nitric oxide production in diabetic mothers, as it is a critical molecular, chemical compound in the development of the heart.

“This is a research project I am really excited about because I am interested in learning more about how it affects the embryo and finding new ways to prevent the development of congenital heart defects in babies of diabetic mothers,” said Dr. Feng.

Speaking about his long-term goals for his cardiac-centred research, Dr. Feng says he would like to develop a drug to remedy cardiac function and increase the survival rate of those affected by heart failure.

“This is a very difficult task, but potentially through our work we can identify the molecules that have a role in heart development and heart failure,” he said.

Acknowledging the importance of perseverance in research, Dr. Feng says he hopes to instill greater sense of critical thinking and scientific exploration in the trainees he supervises in his lab.

“Often we hypothesize something and it doesn’t work out—it’s very common,” he said.

Recalling an experiment he worked on with an MD/PhD trainee, who is one of five trainees he actively supervises, Dr. Feng said, “We worked on a new idea about heart regeneration in a mouse model, and after pursuing it for a year and testing many different hypotheses, in the end it didn’t work out. That doesn’t mean we will never be able to have a breakthrough with this research question, it just means we need to re-evaluate our methods and look at new options.”

Though Dr. Feng hopes the research his trainees are conducting in his lab allows them to foster their research interests and achieve success in their future careers, reflecting on what success means to him, he says, “For me, career success means being recognized in the area I specialize in and gaining recognition on a national, and even international level for my work.”