Background/Aim:

The atrial-specific bone morphogenetic protein 10 (BMP10) has been implicated as a blood biomarker to predict AF-related complications and rhythm in atrial fibrillation (AF). Temporal and quantitative secretion patterns and molecular downstream effects of BMP10 are poorly understood. We set out to experimentally test the hypothesis that BMP10 is secreted by human atrial cardiomyocytes.

Methods:

Two human cardiomyocyte models were assessed: [1] Adult cardiomyocytes: Right atrial, left atrial and left ventricular myocytes were isolated from 16 cardiac specimen of 12 patients undergoing open heart surgery. Freshly isolated cardiomyocytes were cultured on laminin-coated dishes for 48 h. [2] Engineered heart tissue (EHT): Cardiomyocytes differentiated (ventricular or atrial) from human induced pluripotent stem cells (hiPSC) were cast into a fibrin-matrix to generate 24-well format EHT. Atrial EHT were either paced (3-5 Hz) or maintained at intrinsic beating frequency. BMP10 release by cardiomyocytes and EHT into the culture media was studied using ELISA. Gene expression of BMP10 receptors was assessed by qPCR.

Results: 

Human right atrial cardiomyocytes released BMP10 at high concentrations within 3 h of culture, whereas left atrial and left ventricular cardiomyocytes did not release much BMP10 within 48 h (p<0.05 ventricular vs atrial). Congruently, atrial but not ventricular EHT released BMP10 at detectable concentrations within 48 h of culture. Rapid (3-5 Hz) pacing increased BMP10 release ~3-fold (p<0.05 compared to unpaced EHT). ALK-3 and BMPR2, two known BMP10 receptors, were found to be expressed.

Conclusion:

Our experiments confirm that BMP10 is secreted by atrial cardiomyocytes. BMP10 release and downstream signalling effects can be studied in human adult atrial cardiomyocytes and human EHT.