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[Effects of angiotensin II type 1 and type 2 receptor on apoptosis]
Hidehiko Ono1, Toshihiko Ishimitsu
1Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine.
Abstract:
Apoptosis, a morphological form of programmed cell death required for control of cell populations, participates in reduced tissue volume associated with ventricular scarring. Prevention of apoptosis of excessive, damaged, or nonfunctioning cardiac or of infiltrating inflammatory cells is usually beneficial for the resolution of cardiac fibrosis. Angiotensin(Ang) II, the most important peptide that mediates the effects of the renin-angiotensin system, may play an important role in hypertension, hypertrophy, and interstitial fibrosis. Furthermore, AngII induced apoptosis of human venous endothelial cells, myocyte, and vascular smooth muscular cells by caspase cascade activation, and the both blockade of AngII type(AT)1 and AT2 receptor prevents AngII induced apoptosis, whereas selective agonistic stimulation of the AT2 receptor alone induces apoptosis. When AT1 or AT2 receptors are stimulated in vivo, apoptosis is enhanced in myocytes, myofibroblasts, and media smooth muscular cells. In the case of AT1 receptor stimulation, this may occur in cardiac myocytes secondary to ventricular hypertrophy. On the other hand, AT2 receptor stimulation induced apoptosis myofibroblasts associated with reduced interstitial fibrosis. Caspase-3 participates in the pathways of apoptosis triggered by in vivo AT1 and AT2 receptor stimulations.
Insights
Angiotensin II (AngII) promotes apoptosis in cardiac cells via AT1 and AT2 receptors, influencing ventricular scarring and fibrosis. Blocking these receptors or stimulating AT2 alone can modulate apoptosis, impacting cardiac remodeling.
Area of Science:
- Cardiovascular Biology
- Cellular Signaling
- Molecular Medicine
Context:
- Apoptosis, or programmed cell death, is crucial for regulating cell populations and tissue remodeling.
- Cardiac fibrosis and ventricular scarring are pathological conditions often linked to excessive apoptosis.
- The renin-angiotensin system, particularly Angiotensin II (AngII), plays a significant role in cardiovascular diseases like hypertension and hypertrophy.
Purpose:
- To investigate the role of Angiotensin II (AngII) and its receptor subtypes (AT1 and AT2) in mediating apoptosis in cardiac and vascular cells.
- To elucidate the mechanisms of AngII-induced apoptosis, including the involvement of caspase cascades.
- To determine the differential effects of AT1 and AT2 receptor stimulation on apoptosis and cardiac fibrosis in vivo.
Summary:
- Angiotensin II (AngII) induces apoptosis in human venous endothelial cells, myocytes, and vascular smooth muscle cells through caspase cascade activation.
- Both blockade of AngII type 1 (AT1) and Angiotensin II type 2 (AT2) receptors prevent AngII-induced apoptosis.
- In vivo stimulation of AT1 receptors enhances apoptosis in myocytes and smooth muscle cells, potentially secondary to hypertrophy.
- Selective AT2 receptor stimulation induces apoptosis in myofibroblasts, correlating with reduced interstitial fibrosis, while caspase-3 is implicated in both AT1 and AT2 receptor-mediated apoptosis.
Impact:
- Understanding AngII's role in apoptosis provides targets for therapeutic interventions in cardiovascular diseases.
- The differential effects of AT1 and AT2 receptor stimulation offer potential strategies for managing cardiac fibrosis and hypertrophy.
- This research contributes to the mechanistic understanding of programmed cell death in the context of cardiac remodeling and hypertension.