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Angiotensin-converting enzyme 2 attenuates atherosclerotic lesions by targeting vascular cells
- Source :
- Proceedings of the National Academy of Sciences of the United States of America. 107(36)
- Publication Year :
- 2010
-
Abstract
- Angiotensin-converting enzyme 2 (ACE2) is a newly discovered homolog of ACE whose actions oppose those of angiotensin II (AngII). However, the underlying mechanisms by which ACE2 effectively suppresses early atherosclerotic lesions remain poorly understood. Here, we show, both in vitro and in vivo, that ACE2 inhibited the development of early atherosclerotic lesions by suppressing the growth of vascular smooth muscle cells (VSMCs) and improving endothelial function. In a relatively large cohort animal study (66 rabbits), aortic segments transfected by Ad-ACE2 showed significantly attenuated fatty streak formation, neointimal macrophage infiltration, and alleviation of impaired endothelial function. Segments also showed decreased expression of monocyte chemoattractant protein 1, lectin-like oxidized low-density lipoprotein receptor 1, and proliferating cell nuclear antigen, which led to the delayed onset of atherosclerotic lesions. At the cellular level, ACE2 significantly modulated AngII-induced growth and migration in human umbilical vein endothelial cells and VSMCs. The antiatherosclerotic effect of ACE2 involved down-regulation of the ERK-p38, JAK-STAT, and AngII-ROS-NF-κB signaling pathways and up-regulation of the PI3K-Akt pathway. These findings revealed the molecular mechanisms of the antiatherosclerotic activity of ACE2 and suggested that modulation of ACE2 could offer a therapeutic option for treating atherosclerosis.
- Subjects :
- Multidisciplinary
Vascular smooth muscle
Endothelium
Fatty streak
Lipoxygenase
Biology
Peptidyl-Dipeptidase A
Biological Sciences
Atherosclerosis
Angiotensin II
Umbilical vein
medicine.anatomical_structure
Cell Movement
Angiotensin-converting enzyme 2
Immunology
medicine
Cancer research
Humans
Angiotensin-Converting Enzyme 2
Endothelium, Vascular
Signal transduction
Receptor
hormones, hormone substitutes, and hormone antagonists
Chemokine CCL2
Cell Proliferation
Subjects
Details
- ISSN :
- 10916490
- Volume :
- 107
- Issue :
- 36
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....3e58bd71a5b4775a7989e42282c18173