Discovery links gene absence to spongy heart disease

While the heart is developing in utero, certain heart diseases like left ventricular non-compaction (LVNC), also known as spongy heart, can emerge. A University of Houston pharmacology researcher has reported on how cells and molecules act during early heart formation and what might cause LVNC. This type of cardiomyopathy often necessitates heart transplants for patients.

"We found the absence of a certain gene, called Itgb1, may cause inability in the developing heart to maintain its shape and develop normally, causing left ventricular non-compaction," said Mingfu Wu, associate professor at the UH College of Pharmacy, in Cardiovascular Research. "Itgb1 deletion at an early stage causes distinct defects."

Wu's findings involve examining trabeculae—sheet-like structures in developing hearts that protrude from the heart wall. These structures are crucial in early heart development before the coronary system develops because they increase the inner surface area of the heart wall and enhance oxygen and nutrient exchange between blood and the heart wall.

"Without trabeculae, the heart wall would suffer from insufficient oxygen and nutrients, potentially leading to death. Conversely, an excess of trabeculae can result in an overly porous heart wall, leading to left ventricular non-compaction cardiomyopathy," explained Wu.

While some signals controlling trabeculae formation are known, precise mechanisms by which individual cardiac muscle cells (cardiomyocytes) organize to form these structures remain unclear.

"This study reveals that deleting a gene called Itgb1 in heart wall cardiomyocytes prevents trabeculae formation. We found that the protein β1 integrin encoded by Itgb1 and its ligands create a molecular network acting as a scaffold for cardiomyocytes in the heart wall. When Itgb1 is deleted, cardiomyocytes disengage from this scaffold, losing their ability to maintain shape, divide properly, migrate, and form trabeculae," said Wu.

The study suggests that this molecular network may be a common organizational mechanism in organ formation.

"We believe these insights will greatly interest researchers in organ development and regeneration, potentially reshaping our understanding of tissue organization and development," added Wu.

Wu’s collaborators from 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; C. Michael DiPersio from Albany Medical College.

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