Related Experiment Videos
Cellular changes in experimental left heart hypoplasia
David Sedmera1, Norman Hu, Karen M Weiss
1Department of Cell Biology and Anatomy, Medical University of South Carolina, 173 Ashley Avenue, BSB 601, Charleston, SC 29425, USA. sedmerad@musc.edu
Insights
Hypoplastic left heart syndrome (HLHS) development involves reduced cardiomyocyte proliferation. This study in chick embryos shows impaired cell growth, not apoptosis, significantly impacts HLHS pathogenesis.
Area of Science:
- Cardiovascular Biology
- Developmental Biology
- Congenital Heart Disease Research
Background:
- Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect.
- Experimental models are crucial for understanding HLHS pathogenesis.
- Chick embryo models offer a platform for studying cardiac development.
Purpose of the Study:
- To investigate cellular mechanisms underlying ventricular remodeling in a chick embryo model of HLHS.
- To analyze changes in cardiomyocyte proliferation and apoptosis following left atrial ligation (LAL).
- To identify alterations in growth factor expression contributing to HLHS.
Main Methods:
- Induction of HLHS in chick embryos via left atrial ligation (LAL) at stage 24.
- Utilizing 3H-thymidine prelabeling to track cell proliferation.
- Employing autoradiography, immunohistochemistry (anti-myosin), and TUNEL assay for apoptosis detection.
Main Results:
- Left atrial ligation significantly decreased cardiomyocyte proliferation in the left ventricle.
- A slight reduction in proliferation was observed in the right ventricular compact layer; trabeculae were unaffected.
- Myosin expression was reduced, and growth factor levels were altered; apoptosis increased in the atrioventricular mesenchyme, not working myocardium.
Conclusions:
- Reduced cardiomyocyte proliferation is a key factor in the pathogenesis of HLHS.
- The study highlights the role of altered cell proliferation in cardiac malformation.
- Findings suggest therapeutic strategies targeting cardiomyocyte proliferation could be beneficial for HLHS.
Abstract:
Hypoplastic left heart syndrome (HLHS) is a rare but deadly congenital malformation, which can be created experimentally in the chick embryo by left atrial ligation (LAL). The goal of this study was to examine the cellular changes leading to the profound remodeling of ventricular myocardial architecture that occurs in this model. Hypoplasia of left heart structures was produced after 3H-thymidine prelabeling by partial LAL at stage 24, thereby reducing its volume, and redistributing blood preferentially to the developing right ventricle (RV). Controls included both sham-operated and intact stage-matched embryos. Survivors were studied 4 days after the ligation, when the heart organogenesis was essentially complete. Paraffin sections of the hearts were subjected to autoradiography and immunohistochemistry to detect changes in history of cell proliferation and expression of myosin, and growth factors implicated in cardiomyocyte proliferation. Sampling for apoptosis detection using TUNEL assay was done at stages 29 and 34. LAL resulted in decreased levels of proliferation in the left ventricular compact layer and trabeculae. The right ventricular compact layer also showed a slight decrease, but the trabeculae showed no differences. Anti-myosin staining was significantly reduced in all compartments. The expression levels of growth factors were altered as well. Apoptosis was increased in the right atrioventricular mesenchyme, with no changes in the working myocardium. These data suggest that changes in cardiomyocyte proliferation play a significant role in the pathogenesis of HLHS.