RT Journal Article
SR Electronic
T1 Evidence for the role of cell reprogramming in naturally occurring cardiac repair
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.16.342493
DO 10.1101/2020.10.16.342493
A1 Shults, Nataliia V.
A1 Suzuki, Yuichiro J.
YR 2020
UL http://biorxiv.org/content/early/2020/11/21/2020.10.16.342493.abstract
AB Pulmonary arterial hypertension (PAH) is a fatal disease without a cure. If untreated, increased pulmonary vascular resistance kills patients within several years due to right heart failure. Even with the currently available therapies, survival durations remain short. By the time patients are diagnosed with this disease, the damage to the right ventricle (RV) has already developed. Therefore, agents that repair the damaged RV have therapeutic potential. We previously reported that cardiac fibrosis that occurs in the RV of adult Sprague-Dawley rats with PAH could naturally be reversed. We herein investigated the mechanism of this remarkable cardiac repair process. Counting of cardiomyocytes showed that the elimination of cardiac fibrosis is associated with the increased RV myocyte number, suggesting that new cardiomyocytes were generated. Immunohistochemistry showed the expression of α-smooth muscle actin and Sox-2 in RV myocytes of rats with PAH. Transmission electron microscopy detected the structure that resembles maturing cardiomyocytes in both the RV of PAH rats and cultured cardiomyocytes derived from induced pluripotent stem cells. We propose that the damaged RV in PAH can be repaired by activating the cell reprogramming mechanism that converts resident cardiac fibroblasts into induced cardiomyocytes.Competing Interest StatementThe authors have declared no competing interest.