The Extracellular Matrix Proteins Pericardin and Lonely Heart Modulate the Directionality of Heart Contractions in Infected Mosquitoes.

The cardiac extracellular matrix provides structural support to the primary circulatory organ of an insect: a dorsal vessel that is divided into an aorta in the thorax and a heart in the abdomen. In the fruit fly, Drosophila melanogaster, the extracellular matrix components, Pericardin and Lonely heart, are needed for proper heart contractility, as they mediate adhesion between cardiomyocytes, pericardial cells, hemocytes, and alary muscles. In the mosquito, Anopheles gambiae, Pericardin and Lonely heart are necessary for the infection-induced migration of hemocytes to the heart. In these infected mosquitoes, hemocytes decrease the heart rate by releasing nitric oxide. Here, we demonstrate in mosquitoes that Pericardin is transcribed throughout the abdomen, but that Lonely heart is transcribed mainly in the heart. Moreover, we demonstrate that Pericardin and Lonely heart influence the infection-induced disproportional decrease in the anterograde and retrograde heart rates. We also demonstrate that, in infected mosquitoes, Pericardin and Lonely heart alter the directionality of heart contractions, shifting to more contractions propagating anterograde. These findings further explain how the immune and circulatory systems of insects are functionally integrated by demonstrating that the cardiac extracellular matrix, in addition to driving hemocyte organization on the heart, modulates heart rhythmicity in infected mosquitoes.