New Treatment Strategies Using Ventricular and Atrial Myocytes

Human cardiomyocytes (CMs) are derived from human pluripotent stem cells (hPSCs) and are now an influential source for cardiac regeneration. Significant interest in CHms has been the focus of studies that are cardiac disease drug-related.

Immunofluorescent analysis of (4% PFA) fixed mouse heart tissue using 21652-1-AP (Cardiac Troponin I antibody) at dilution of 1:50 and Alexa Fluor 488-conjugated AffiniPure Goat Anti-Rabbit IgG(H+L).

Immunofluorescent analysis of (4% PFA) fixed mouse heart tissue using 21652-1-AP (Cardiac Troponin I antibody) at dilution of 1:50 and Alexa Fluor 488-conjugated AffiniPure Goat Anti-Rabbit IgG(H+L).  Image Credit: Proteintech Group, Inc.

Most are distinguished by spontaneous beating, exhibiting a wide range of depolarization-repolarization patterns, potentially indicating mixed populations of atrial and ventricular myocytes.

Which is more important: atrial or ventricular myocytes?

The muscular walls of the heart, also known as the myocardium, are formed from atrial and ventricular cardiomyocytes. Differences can be seen in atrial myocyte ultrastructure when compared to ventricular myocytes.

Atrial and ventricular cardiomyocytes have differential gene expression patterns concerning, for example, transcription factors, structural proteins, and ion channels.

Additionally, they exhibit specific functions, as seen in Table 1, and highly homogeneous atrial- and ventricular-like myocytes are very helpful for drug safety, cardiac evaluation, and heart infarction cell therapies.

Table 1. Differential gene expression pattern displays in atrial and ventricular cardiomyocytes. Source: Proteintech Group, Inc.

Gene Chamber/Gene expression Functions
HRT1/HEY1 Atria Transcriptional repressor of GATA4/6, ANF, BMP2, TBX2; Precise formation of the atrioventricular boundary
HRT2/HEY2 Ventricles Transcriptional repressor of GATA4/6, ANF, BMP2, TBX2, CX40, TBX5, ALC-1, MLC-2a;
Formation of the atrioventricular canal;
Maintain normal contractility of the ventricles
MYL7/MLC-2a Atria Form cardiac sarcomere; Maintenance of atrial contractility
MYL2/MLC-2v Ventricles Form cardiac sarcomere; Maintenance of ventricular contractility
Sarcolipin/
SLN
Atria Regulate calcium cycling (decrease SR calcium transport by inhibiting SERCA)
KCNE1 Ventricles Accessory (beta) subunit of the pore-forming (alfa) KCNQ1 that encodes the Iks
ANF/HESX1 Atria Control blood pressure, renal function, salt balance

 

Distinguishing atrial and ventricular cardiomyocytes

Within the ventricular segment of the heart, the ventricular myosin light chain-2 isoform (MYL2/MLC-2v), as seen in Figure 1, can be found. It is limited to this segment and is linked to the ventricles during its development.

Conversely, the atrial myosin light chain-2 (MYL7/MLC-2a), as seen in Figure 2, is expressed in the presumptive ventricle before MYL2/MLC-2v. Its expression in the ventricle is then down-regulated as an alternative, with abundant expression in the atrium postnatally.

A specific marker for ventricle and atrial cardiomyocytes is found through the expression pattern of MYL2/MLC-2v and MYL7/MLC-2a. It is common for it to be utilized for in vitro development of induced pluripotent stem cell-derived cardiomyocytes (iPSC-Derived Cardiomyocytes).

IHC results of paraffin-embedded human heart tissue using MYL2 Antibody (10906-1-AP; 1:200, 40x).

Figure 1. IHC results of paraffin-embedded human heart tissue using MYL2 Antibody (10906-1-AP; 1:200, 40x). Image Credit: Proteintech Group, Inc.

IF analysis of fixed mouse heart tissue using MYL7 Antibody (17283-1-AP; 1:50, 40x).

Figure 2. IF analysis of fixed mouse heart tissue using MYL7 Antibody (17283-1-AP; 1:50, 40x). Image Credit: Proteintech Group, Inc.

Remodeling of cardiomyocytes and treatment strategies

Patients who have had myocardial infarction are consequentially suffering from heart failure and their heart function deteriorates, leading to a significant loss of ventricular cardiomyocytes. Because of this, a huge amount of mature ventricular myocytes are required for myocardial infarction treatment.

Although there are effective therapies available for common disorders of atrial cardiomyocytes, like atrial fibrillation, loss of ventricular cardiomyocytes as a result of myocardial infarction is unable to be successfully treated. Therefore, demand is high for a source of ventricular cardiomyocytes.

Recent research using the atria of zebrafish suggests that the activation of Notch signa­ling as a response to ventricle ablation is essential for the reprogramming of atrial cardiomyocytes into ventricular cardiomyocytes.

It is proposed from this study that heart regeneration in zebrafish can be attained by transdifferentiation of differentiated atrial cardiomyocytes into ventricular cardiomyocytes.

A detailed understanding of the molecular and functional variances between atrial and ventricular cardiomyocytes is helpful in defining novel techniques for applications of embryonic stem cells (ESCs), as well as providing cellular models for research into genetic atrial- or ventricular-related diseases.

It is possible to use the programmed differentiation of atrial- and ventricular-like myocytes for the development of safe cell sources for individual treatment and cardiac repair that is personalized.

References

  1. A Universal and Robust Integrated Platform for the Scalable Production of Human Cardiomyocytes From Pluripotent Stem Cells.
  2. Atrial and ventricular myocytes.
  3. Differential gene expressions in atrial and ventricular myocytes: insights into the road of applying embryonic stem cell-derived cardiomyocytes for future therapies.
  4. Chamber specification of atrial myosin light chain-2 expression precedes septation during murine cardiogenesis.
  5. The “heart” of science.
  6. In vivo cardiac reprogramming contributes to zebrafish heart regeneration.
  7. The human adult cardiomyocyte phenotype.

About Proteintech Group, Inc Proteintech Group, Inc

Proteintech are a global biotech company and a renowned center of excellence for the manufacture and supply of quality antibodies, ELISA kits and proteins to the life science research community.

With offices in the US (Chicago), UK (Manchester) and China (Wuhan) Proteintech are always available to support your research. Part of Proteintechs early vision was to make all its own products, to the highest standards possible and to take complete responsibility for the quality. With an emphasis on developing antibodies from whole proteins, Proteintech provides researchers with unmatched reliability and reproducibility.


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Last updated: Mar 23, 2020 at 7:26 AM

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