Key Takeaways:
University of Houston researcher Mingfu Wu has received a $3.1 million National Institutes of Health (NIH) grant to investigate left ventricular noncompaction (LVNC), a serious heart condition also known as "spongy heart" that can lead to heart failure and abnormal heart rhythms.
The UH College of Pharmacy research will examine how "spongy heart" develops, including whether abnormal movement and growth of heart-muscle cells during development contributes to the condition.
The study could uncover a common mechanism behind different genetic causes of LVNC, potentially identifying new targets for future treatments rather than focusing on a single genetic use.
The new NIH grant brings Wu's NIH funding for LVNC research to approximately $8 million over the past decade, advancing the University of Houston's research into heart development and potential approaches to treating cardiovascular disease.
Mingfu Wu, professor of pharmacology at the University of Houston, has received a $3.1 million grant from the National Institutes of Health to study how left ventricular noncompaction, commonly known as "spongy heart," disease develops in children. The serious condition can lead to heart failure, abnormal heart rhythms and other complications. Wu's study will investigate what causes the heart to develop abnormally and whether the biological processes involved could one day be interrupted.
Wu has received three major NIH grants over the past decade to study the condition, bringing his total funding to $8 million.
LVNC affects the heart’s ability to develop a normal, compact muscle wall. In people with the condition, the left ventricle is spongy and thick, rather than smooth and firm. Mortality rates reported for LVNC range from 5% to 47%.
Wu is investigating what happens inside the developing heart that causes its left ventricle to develop improperly, causing an inability in the heart to contract and relax properly and to efficiently pump blood which can lead to heart failure and other serious complications. He will focus on whether the movement and growth of heart-muscle cells and the signals that control them drive the excessive ridges and deep spaces (called trabeculae) characteristic of the disease.
Perhaps nothing in the formation of the heart is more important than trabeculae, which help the heart pump blood. Lack of trabeculation causes embryonic demise, and excess trabeculation can cause a spongy heart.
But how?
“Our hypothesis is that a particular group of heart muscle cells moves from the compact outer layer into the inner trabecular layer. These cells then multiply and contribute to excessive trabeculation,” said Wu. “We will track these cells directly to determine whether this abnormal relocation is a central mechanism of the disease."
The new study investigates the cellular behavior and signaling pathways that may connect different causes of spongy heart disease—and, importantly, whether those pathways can be targeted therapeutically.
Wu’s new research builds on earlier discoveries by his team about the genetic and cellular processes involved in normal heart development. Rather than focusing on a single genetic cause of LVNC, the new study examines whether different causes of the disease may ultimately trigger a common cellular process that produces the characteristic spongy structure.
“Our previous studies showed that loss of Numb Family Proteins in heart muscle cells can cause left ventricular noncompaction. We also found that deletion of Itgb1 and Prdm16 disrupts the organization and shape of developing heart muscle cells, leading to abnormal ventricular wall development,” said Wu.
Those studies helped identify genes that are important for normal heart formation.
Wu will also investigate a different molecular pathway involving beta-adrenergic receptors, which respond to stress signals, and the downstream NRG1-ErbB2/ErbB4 pathway. Preliminary results suggest that excessive activation of these pathways may drive abnormal cell movement and growth.
The Wu team will also test whether blocking these signals can prevent or reduce the disease.