Research

Mechano-Chemo-Transduction

Cardiomyocytes contract against a mechanical load during each heartbeat. We developed a 3-D Cell-in-Gel system top apply mechanical afterload during cardiomyocyte contraction. We discovered that the nitric oxide synthase 1 (NOS1, or nNOS) was involved in transducing mechanical load to alter Ca²⁺ signaling in cardiomyocytes. Mechanical load increased the systolic Ca²⁺ transient, which enhanced contractility to counter the load increase. Mechanical load also caused spontaneous Ca²⁺ sparks and waves during diastole that are arrhythmogenic. We also identify NOS1, Nox2, and CaMKII as chemo-transducers in the mechano-chemo-transduction, which provides new therapeutic targets for treating cardiac arrhythmias and heart failure associated with high mechanical stresses (i.e., high blood pressure, HFrEF, HFpEF, etc.)