Investigating how the heart forms in utero, pharmacology researchers at the University of Houston report how cells and molecules act during that early formation and what causes a heart condition called left ventricular noncompaction, also known as cavernous heart, a type of heart muscle disease (or cardiomyopathies) that often requires a heart transplant.
“We found that a defect in a specific gene called Itgb1 can cause the developing heart to fail to maintain its shape and develop normally, leading to left ventricular noncompaction,” Ming-Hu Wu, an associate professor at the University of Hawaii’s College of Pharmacy, reports in the journal Cardiovascular Research. “Deletion of Itgb1 at an early stage causes a distinct defect.
Dr. Wu’s research findings involved the examination of trabecular bone, sheet-like structures that protrude from the heart wall during heart development. These structures are crucial for supplying blood to the developing heart early on, before the coronary artery system has developed, as they increase the heart wall’s internal surface area and facilitate the exchange of oxygen and nutrients between the blood and the heart wall.
“Without trabecular bone, the heart wall would be starved of oxygen and nutrients, which could lead to death. Conversely, too much trabecular bone could cause the heart wall to become excessively porous, leading to a type of left ventricular noncompact cardiomyopathy known as cavernous heart,” Wu said.
Although the specific signals that control trabecular formation are known, the exact mechanisms by which the individual cells that make up the cardiac muscle (cardiomyocytes) organize to form these structures remain unclear.
“This study revealed that deleting a gene called Itgb1 in cardiomyocytes in the heart wall prevents trabecular bone formation. We found that the protein encoded by Itgb1, β1 integrin, and its ligand, the extracellular matrix, form a molecular network that acts as a scaffold for cardiomyocytes in the heart wall. When Itgb1 is deleted, cardiomyocytes detach from this scaffold and lose their ability to maintain their shape, divide properly, migrate, and form trabecular bone,” Wu said.
This study suggests that molecular networks may be a common organizing mechanism in organ development.
“We believe these findings will be of great interest to researchers studying organ development and regeneration and have the potential to revolutionize our understanding of tissue organization and development,” Wu said.
Wu’s collaborators at the University of Houston include Lianjie Miao, Yangyang Lu, Anika Nusrat, Luqi Zhao, Micah Castillo, Yongqi Xiao, Hongyang Guo, Yu Liu, Preethi Gunaratne, Robert, J Schwartz, Alan R Burns, Ashok Kumar, and C. Michael DiPersio (Albany Medical College).
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