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Identification and activation of autocrine renin-angiotensin system in adult ventricular myocytes
1Department of Medicine, New York Medical College, Valhalla 10595, USA.
Abstract:
To date, the demonstration that the molecular components of the renin-angiotensin system (RAS) are present in adult ventricular myocytes is lacking. In addition, whether the RAS is upregulated under conditions of overload and myocyte hypertrophy in vivo remains to be determined. By employing an in vivo model of ischemic cardiomyopathy in rats, we document that adult myocytes express genes for renin, angiotensinogen, angiotensin-converting enzyme (ACE), and angiotensin II (ANG II) receptors. Moreover, renin, ACE, and ANG II receptor mRNAs increased in stressed myocytes undergoing cellular hypertrophy. At the protein level, the percentage of myocytes containing renin, ANG I, and ANG II was significantly increased in the overloaded heart. The number of binding sites for ANG II per myocyte also markedly increased under this setting. These results provide direct evidence of the existence of a myocyte RAS, which may be activated in pathological states of the heart to support myocyte growth and contractile function.
Insights
Adult heart cells possess the molecular machinery for the renin-angiotensin system (RAS). This cardiac RAS is activated during heart stress and hypertrophy, suggesting a role in supporting myocyte growth and function.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Renin-Angiotensin System Research
Background:
- The presence and function of the renin-angiotensin system (RAS) components within adult ventricular myocytes have not been definitively demonstrated.
- The upregulation of the cardiac RAS under conditions of heart overload and myocyte hypertrophy in vivo remains an open question.
Purpose of the Study:
- To investigate the expression of RAS molecular components in adult ventricular myocytes.
- To determine if the cardiac RAS is upregulated in response to in vivo models of heart overload and myocyte hypertrophy.
Main Methods:
- Utilized an in vivo rat model of ischemic cardiomyopathy.
- Analyzed gene expression (mRNA) for renin, angiotensinogen, angiotensin-converting enzyme (ACE), and angiotensin II (ANG II) receptors in myocytes.
- Assessed protein levels of renin, ANG I, and ANG II, as well as ANG II receptor binding sites in overloaded hearts.
Main Results:
- Adult myocytes were found to express genes for key RAS components: renin, angiotensinogen, ACE, and ANG II receptors.
- mRNA levels for renin, ACE, and ANG II receptors increased in stressed myocytes experiencing hypertrophy.
- Protein analysis revealed a significant increase in myocytes containing renin, ANG I, and ANG II, along with a marked rise in ANG II binding sites per myocyte in overloaded hearts.
Conclusions:
- Provided direct evidence for the existence of a functional renin-angiotensin system within myocytes (myocyte RAS).
- The myocyte RAS appears to be activated in pathological cardiac conditions, such as hypertrophy and overload.
- This activated myocyte RAS may play a crucial role in promoting myocyte growth and maintaining contractile function during cardiac stress.