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Indexes of Angiogenic Activation in Myocardial Samples of Patients with Advanced Chronic Heart Failure
Klara Komici1, Isabella Gnemmi2, Claudia Sangiorgi2
1Department of Medicine and Health Sciences, University of Molise, 86100 Campobasso, Italy.
Insights
This study compared pro-angiogenic molecule expression in heart failure patients. Angiopoietin-2 levels were higher in ischemic cardiomyopathy, suggesting altered endothelial integrity in this heart failure type.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Heart Failure Pathophysiology
Background:
- Ischemic and idiopathic heart failure involve cardiac fibrosis and impaired vasculogenesis.
- Pro-angiogenic factors like angiogenin, angiopoietin-1 (Ang-1), and angiopoietin-2 (Ang-2) are implicated in heart failure models.
- Molecular pathway differences between ischemic and non-ischemic cardiomyopathies remain unclear.
Purpose of the Study:
- To compare the expression of pro-angiogenic molecules in heart tissue from patients with advanced chronic heart failure (CHF) of ischemic versus non-ischemic etiology.
- To investigate potential differences in angiogenic signaling pathways between ischemic (ICM) and non-ischemic dilated cardiomyopathy (NIDCM).
Main Methods:
- Heart tissue samples were obtained from 16 explanted native hearts (ICM and NIDCM) during transplantation.
- Immunohistochemistry was used to examine the expression and localization of angiogenic molecules (angiogenin, Ang-1, Ang-2, Tie-2 receptor).
Main Results:
- Angiopoietin-1 (Ang-1) was primarily found in cardiomyocytes; Ang-2 and Tie-2 receptor were mainly in endothelial cells.
- Expression of Procollagen-I (PICP), angiogenin, Ang-1, and Tie-2 receptor was similar between ICM and NIDCM.
- Endothelial immunopositivity for Ang-2 was significantly higher in ICM compared to NIDCM (p = 0.03).
Conclusions:
- Ang-1 and angiogenin are predominantly expressed in cardiomyocytes, while Ang-2 is mainly in endothelial cells in CHF samples.
- Higher Ang-2 expression in endothelial cells of ICM suggests distinct angiogenic stimulation patterns or altered endothelial integrity in ischemic heart failure.
- These findings contribute to understanding angiogenesis signaling in CHF and highlight potential differences between ICM and NIDCM.
Abstract:
Background and objectives: Ischemic and idiopathic heart failure are characterized by reactive cardiac fibrosis and impaired vasculogenesis involving pro-angiogenic factors such as angiogenin, angiopoietin-1 (Ang-1), and angiopoietin-2 (Ang-2), as demonstrated in experimental models of heart failure. However, differences in the molecular pathways between these cardiomyopathies are still unclear. In this short communication, we evaluate and compare the expression of pro-angiogenic molecules in the heart tissue of patients with advanced chronic heart failure (CHF) of ischemic vs. nonischemic etiology. Materials and Methods: We obtained heart tissue at transplantation from left ventricular walls of 16 explanted native hearts affected by either ischemic (ICM) or nonischemic dilated cardiomyopathy (NIDCM). Tissue samples were examined using immunohistochemistry for angiogenic molecules. Results: We found immunopositivity (I-pos) for angiopoietin-1 mainly in the cardiomyocytes, while we observed I-pos for Ang-2 and Tie-2 receptor mainly in endothelial cells. Expression of Procollagen-I (PICP), angiogenin, Ang-1, and Tie-2 receptor was similar in ICM and NIDCM. In contrast, endothelial immunopositivity for Ang-2 was higher in ICM samples than NIDCM (p = 0.03). Conclusions: In our series of CHF heart samples, distribution of Ang-1 and angiogenin was higher in cardiomyocytes while that of Ang-2 was higher in endothelial cells; moreover, Ang-2 expression was higher in ICS than NIDCM. Despite the small series examined, these findings suggest different patterns of angiogenic stimulation in ICM and NIDCM, or at least a more altered endothelial integrity in ICD. Our data may contribute to a better understanding of the angiogenesis signaling pathways in CHF. Further studies should investigate differences in the biochemical processes leading to heart failure.
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