More than 40,000 babies in the United States, or about 1 in 100 births, are born annually with a congenital heart defect. Congenital heart defect, is a problem in the structure of the heart that is present at birth. Signs and symptoms depend on the specific type of problems, such as rubella infection, obesity or drug-abuse, with complications including heart failure. The problems may involve the interior walls of the heart, the heart valves, or the large blood vessels that lead to and from the heart.
Despite heart defects being the most common and leading cause of birth defect-related death, the cause of a congenital heart defect is often unknown. Now, a study from researchers at Cornell has shown that natural triggers could reduce the chance of life-threatening, congenital heart defects among newborn infants. The team state that those triggers can override developmental, biological miscues, leading to proper embryonic heart and valve formation. The opensource study is published in the journal Current Biology.
Previous studies show that the heart is the first organ to form in the embryo, where it morphs dynamically and rapidly, all the while pumping nutrients to the developing body. The early embryonic heart originates as a looped tube, without valves or pumping chambers. During the last few weeks of the first trimester, these heart chambers form, whilst maintaining one-way blood flow. Wispy globular masses, called cushions due to their shape in the heart wall, need to condense and elongate to form thin robust leaflets capable of fast, resilient opening and closing; it is this valve maturation process that’s likely disrupted in many clinical cases. Past research shows that the embryonic heart needs blood flow to grow, however, the valve component’s role isn’t entirely understood. The current study shows how mechanical forces drives the biological remodeling of cushions into these critical valves.
The current study shows that cyclical stretch and stress forces activate sensitive GTPases enzymes, called RhoA and Rac1, which coordinate the embryonic heart’s maturation. Results show that without these enzymes activating at the proper times, heart valves do not form correctly.
Results show that RhoA controls myofibroblastic activation during early valve development and Rac1 mediates matrix compaction through cell elongation and stress-fiber alignment. Data findings show that mechanical stretch regulates the transition between RhoA and Rac1 via FilGAP. The lab state that cyclical mechanical signaling coordinates the RhoA to Rac1 signaling transition essential for proper embryonic mitral valve remodeling.
The team surmise that they’ve identified a mechanism that translates a mechanical force into a biological response and that biological response over time creates these thin, flexible, formative leaflets. They go on to add that if this tissue fails to get thinner and/or elongate, that’s a problem. For the future, the researchers state that this work lays a foundation for hemodynamically informed surgical interventions to potentially retard valve malformation, or to restore it.
Source: Cornell Chronicle