Remodeling of Cardiomyocytes: Study of Morphological Cellular Changes Preceding Symptomatic Ischemic Heart Failure
Milda Kuprytė1, Vaiva Lesauskaitė2, Vytenis Keturakis1
1Laboratory of Cardiac Pathology, Institute of Cardiology, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania.
Insights
Early structural changes in heart muscle cells (cardiomyocytes) and their internal scaffolding occur before symptomatic ischemic heart failure (HF). These remodeling events involve significant alterations in size, shape, and desmin expression, offering insights into HF pathogenesis.
Area of Science:
- Cardiovascular Biology
- Cellular Morphology
- Pathophysiology
Background:
- Heart failure (HF) pathogenesis mechanisms are known, but early cardiomyocyte changes preceding symptoms are unclear.
- Understanding early structural cardiomyocyte remodeling is crucial for identifying therapeutic targets in ischemic HF.
Purpose of the Study:
- To characterize morphological changes in cardiomyocytes.
- To investigate intermediate filament reorganization during preclinical ischemic heart failure.
- To analyze desmin expression in relation to HF stages.
Main Methods:
- Histomorphometric and immunohistochemical analysis of 84 human heart tissue samples.
- Evaluation of cardiomyocyte size, shape, and desmin expression.
- Categorization of samples into ACC/AHA HF Stages A, B, and C/D.
Main Results:
- Cardiomyocyte size and volume increased significantly from Stage A HF, primarily in diameter, and further in Stage C/D HF, mainly in length.
- Desmin expression elevated in Stage A HF and peaked in Stages C/D HF.
- Significant cardiomyocyte morphological changes and cytoskeletal reorganization precede symptomatic ischemic HF.
Conclusions:
- Early, adaptive structural changes in cardiomyocytes and their cytoskeletal network are evident before symptomatic ischemic heart failure.
- These findings highlight the importance of early cellular remodeling in HF development.
- Characterization of these preclinical changes provides a foundation for future diagnostic and therapeutic strategies.
Abstract:
Although major pathogenesis mechanisms of heart failure (HF) are well established, the significance of early (mal)adaptive structural changes of cardiomyocytes preceding symptomatic ischemic HF remains ambiguous. The aim of this study is to present the morphological characterization of changes in cardiomyocytes and their reorganization of intermediate filaments during remodeling preceding symptomatic ischemic HF in an adult human heart. A total of 84 myocardial tissue samples from middle-left heart ventricular segments were analyzed histomorphometrically and immunohistochemically, observing the cardiomyocyte's size, shape, and desmin expression changes in the remodeling process: Stage A of HF, Stage B of HF, and Stages C/D of HF groups (ACC/AHA classification). Values p < 0.05 were considered significant. The cellular length, diameter, and volume of Stage A of HF increased predominantly by the diameter vs. the control group (p < 0.001) and continued to increase in Stage B of HF in a similar pattern (p < 0.001), increasing even more in the C/D Stages of HF predominantly by length (p < 0.001). Desmin expression was increased in Stage A of HF vs. the control group (p < 0.001), whereas it was similar in Stages A and B of HF (p > 0.05), and most intense in Stages C/D of HF (p < 0.001). Significant morphological changes of cardiomyocytes and their cytoskeletal reorganization were observed during the earliest remodeling events preceding symptomatic ischemic HF.
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