A membrane-remodeling enzyme helps heart muscle maintain its contraction
A peer-reviewed study links the enzyme LPLAT7, also called LPGAT1, to the lipid composition and contraction of heart muscle. Removing its gene from male mouse cardiomyocytes altered selected membrane molecules and impaired cardiac function. Cell experiments connected the changes with calcium signaling, while increasing enzyme expression partly improved a separate mouse model of pressure-related heart dysfunction.
Science··Morning
Changing membrane molecules weakens contraction
Removing the gene for LPLAT7, an enzyme that remodels membrane phospholipids, impaired heart contraction in male mice. Also called LPGAT1, the enzyme changes fatty-acid composition in two major membrane components, phosphatidylcholine and phosphatidylethanolamine. The single peer-reviewed study found reductions in selected molecules containing docosahexaenoic acid together with stearic acid. Although the molecular mixture changed, most major lipid pools remained intact. The mice showed impaired left-ventricular contraction and increased heart-failure-associated gene signals.[1]
Calcium signals respond to partial rescue
Molecular analyses implicated protein kinase A (PKA), an enzyme involved in cell signaling, and abnormal calcium handling. Reducing LPLAT7 in heart cells grown from human induced pluripotent stem cells also changed calcium transients. Blocking PKA with H89 brought partial improvement in cardiac function and calcium handling in the tested systems. Partial rescue supports involvement of that pathway without resolving the entire mechanism.[1]
More enzyme partly improves pressure-loaded mouse hearts
Increasing enzyme expression partly improved heart function in a separate mouse experiment that imposed pressure load by narrowing the aorta. Improvement accompanied selective recovery of the membrane molecule PC(40:6), rather than restoration of the entire phospholipid pool. An observational comparison also found reduced enzyme expression in 21 human hearts with dilated cardiomyopathy versus eight non-failing hearts. The experimental interventions were in animal and cell systems; the study did not test dietary supplementation or a treatment for patients.[1]
