Cardiac Cells in Regenerative Processes in Patients with Heart Failure Due to Ischaemic Heart Disease
O. V. Stepanova *
Cardiology Research and Production Center, Moscow, Russia and V. Serbsky Federal Medical Research Centre of Psychiatry and Narcology, Moscow, Russia.
T. G. Kulikova
Cardiology Research and Production Center, Moscow, Russia.
M. P. Valikhov
Cardiology Research and Production Center, Moscow, Russia.
R. A. Poltavtseva
Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia.
A. A. Shiryaev
Cardiology Research and Production Center, Moscow, Russia.
V. P. Masenko
Cardiology Research and Production Center, Moscow, Russia.
V. P. Chekhonin
V. Serbsky Federal Medical Research Centre of Psychiatry and Narcology, Moscow, Russia.
G. T. Sukhikh
Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia.
*Author to whom correspondence should be addressed.
Abstract
Aims: This study aimed to find the cardiac cells which can participate in the processes of regeneration at patients with heart failure due to ischaemic heart disease. To investigate the participation of myosin activating protein kinases in sarcomerogenesis, because sarcomerogenesis is the crucial part of cardiomyocyte differentiation process.
Study Design: Resident cardiomyocyte progenitors and dedifferentiated cardiomyocytes were found in left atrial appendages from patients with heart failure due to ischaemic heart disease. We used a cell model of fetal cardiomyocytes with the disassembly contractile apparatus to study the forming of new myofibrils (or sarcomerogenesis) regulated by myosin activating protein kinases.
Place and Duration of Study: Cardiology Research and Production Center, Research Center for Obstetrics, Gynecology and Perinatology, Department of Fundamental and Applied Neurobiology of V. Serbsky Federal Medical Research Centre of Psychiatry and Narcology between June 2014 and October 2015.
Methodology: We included 10 patients with heart failure due to ischaemic heart disease. Resident cardiomyocyte progenitors and dedifferentiated cardiomyocytes were found by the immunofluorescence approach and the electron microscopy. To determine the myosin activating protein kinases localization in human fetal cardiomyocytes at the 8-9 week heart gestation stage immunofluorescence approach was used.
Results: We detected the cardiomyocyte progenitor cells which express c-Kit and Nkx-2.5, other cells express Mdr-1 and GATA-4. Dedifferentiated cardiomyocytes were found. It has been established that smooth muscle, nonmuscle and skeletal myosin light chain kinases are colocalized with nonmuscle myosin in premyofibrils in fetal human cardiomyocytes.
Conclusion: We demonstrated that the heart of patients with heart failure due to ischaemic heart disease contains the progenitor resident cardiomyocytes and dedifferentiated cardiomyocytes. These cardiac cells possibly can proliferate and differentiate to mature cardiomyocytes and recover heart function and structure after injury. Myosin activating protein kinases may contribute in myofibril formation during the cardiomyocyte differentiation.
Keywords: Resident cardiomyocyte progenitors, dedifferentiated cardiomyocytes, regeneration, redifferentiation, myosin activating protein kinases, ischaemic heart disease, heart failure.