Abstract
Right ventricular (RV) failure is the major cause of death among patients with pulmonary hypertension. However, differences between the RV and left ventricle (LV) of the adult heart have not been defined, despite myocytes from these two ventricles originate from different progenitor cells. The lack of such knowledge interferes with developing therapeutic strategies to protect the RV. The goal of this study was to identify possible differences between stress responses in the RV and LV free walls of adult rats. We found that levels of angiogenesis and autophagy/mitophagy proteins are higher in the LV than in the RV. Thus, the LV may be more resistant to stress-induced damage. To test this, isolated rat hearts were subjected to biventricular working heart perfusion and ischemia/reperfusion (I/R) injury. However, I/R was found to cause apoptosis in both LV and RV to a similar extent. One mechanism of cardiac apoptosis involves downregulation of GATA4 transcription factor that controls gene transcription of anti-apoptotic Bcl-xL. Interestingly, only in the RV, I/R caused downregulation of GATA4 and Bcl-xL, suggesting that mechanisms of apoptosis may be different between the two ventricles. Levels of tropomyosin and troponin T were also found to be decreased in response to I/R only in the RV, but not in the LV. Downregulation of the GATA4/Bcl-xL axis and the reduction of tropomyosin and troponin T are RV-specific events that occur in response to stress. This information may be useful for designing RV-specific therapeutic strategies to treat RV failure in pulmonary hypertension patients.
Highlights
The pathophysiology of the left ventricle (LV) is well understood and has been considered to represent that of the heart, in general
We found that levels of angiogenesis and autophagy/mitophagy proteins are higher in the LV than in the Right ventricular (RV)
We found that the expression of vascular endothelial growth factor (VEGF), a major contributor in increasing the number of capillaries during angiogenesis, is significantly higher in the LV free wall compared to the RV free wall in healthy rat hearts (Figure 1A)
Summary
The pathophysiology of the left ventricle (LV) is well understood and has been considered to represent that of the heart, in general. Despite the right heart failure is the major cause of death among patients with pulmonary hypertension, the right ventricle (RV) has not been well studied[1]. Apparent mechanisms of heart failure in the right and left sides of the heart, in response to pulmonary and systemic hypertensions, respectively, are different. Concentric hypertrophy of the LV transitions to LV dilation with eccentric cardiac hypertrophy and thinning of the LV wall. The failed RVs in cor pulmonale have the structure of the concentrically hypertrophied RV2,3. Understanding the RV biology should help developing new therapeutic strategies for cardiovascular diseases, in particular, pulmonary hypertension
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