May 18, 2000 Penn State medical researchers have found low blood-plasma levels of nitric oxide (NO) in mouse newborns, which are born with hypoplastic or abnormal lungs, the first study to show such a relationship.
"Nitric oxide is a molecule that is important for dilating or opening up the pulmonary blood vessels to allow proper blood flow through these micro-vessels in the lungs, which facilitates the purification of blood through sufficient gas exchange," says Dr. Mala R. Chinoy, Ph.D., associate professor of surgery and director of the study.
Chinoy and her colleagues believe that endogenous nitric oxide plays a significant role in the structural development of blood vessels during the embryonic stages when low levels of NO lead to vascular smooth muscle proliferation. In the newborns, (this proliferation leads ) to a thickened smooth muscle layer around the blood vessels in the lungs interferes with proper blood flow, thus resulting in the persistent pulmonary hypertension (PPH) or elevated blood pressure, and respiratory distress due to hampered function of the lungs.
"We are using high throughput screening technology called DNA / gene chip microarray to identify the differentially expressed genes in the normal and abnormal lungs," Chinoy says. "The data collection allows us to analyze thousands of genes simultaneously. We ultimately want to identify the candidate genes affecting specific functional and developmental pathways of lung." She also hopes to discover some novel genes by using this approach.
Chinoy is presenting her work titled, "Differential Lung Gene Expression in Experimental Congenital Diaphragmatic Hernia," at The American Thoracic Society 2000, the 96th International Conference in Toronto this week.
Chinoy and her colleagues have a mouse model of this human condition, which they use to study abnormal lung development. In the past four years, they have found several similarities between human babies born with pulmonary hypoplasia (PH) or small insufficient lungs, with coexistent congenital diaphragmatic hernia (CDH), and the mouse model that they have established. Affected human and mouse newborns have defects of heart and lung and microvasculature of the lung (network of small vessels which supply blood to the lung). Proper development of vasculature is crucial to gas exchange in the air-breathing lungs.
Recent studies from Chinoy's laboratory have shown that in the affected mouse newborns, certain compensatory mechanisms are kicked in by the body to overcome these problems, but due to the impairment of the specific genes and proteins during the embryonic stages, these mechanisms cannot fully compensate for the existing defects and the babies suffer from PPH and respiratory distress.
The researcher hopes that the future work in this area will focus on understanding the defective embryonic development of heart, lung and blood vessel formation in lungs. More detailed work in this field will open avenues to help treat defects in unborn babies and in the long run prevent the fatal outcome of this defect in newborn babies.
The American Lung Association (Pennsylvania Chapter), American Heart Association (National Center) and Bayer Pharmaceutical Company currently fund Chinoy's research.
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