Expression of CYR61, an Angiogenic Immediate Early Gene, in Arteriosclerosis and Its Regulation by Angiotensin II
Abstract
Background — The renin-angiotensin system is thought to be involved in development and progression of arteriosclerosis, thereby contributing to adverse cardiovascular events. To elucidate the role of angiotensin II (Ang II) at a cellular level, we analyzed the Ang II–induced gene expression profile. Methods and Results — Genes induced on Ang II stimulation (10 −7 mol/L, 45 minutes) in rat smooth muscle cells were analyzed by polymerase chain reaction selected subtraction. In addition to known genes, such as interleukin 6, leukemia inhibitory factor , and c- fos , we identified CYR61 , an angiogenic immediate early gene. Northern blot analysis revealed a rapid 2.5-fold increase of CYR61 transcript levels by Ang II, peaking at 30 minutes, which was blunted by Ang II type 1 receptor blockade. Exposure of rat aortic rings to Ang II (30 minutes) revealed a 2-fold, and intraperitoneal injection of Ang II (30 minutes) in mice a 3-fold, increase of aortic CYR61 transcripts. In arteriosclerotic aortas of apolipoprotein E–deficient mice, CYR61 transcripts confirmed by in situ hybridization and proteins shown by immunohistochemistry were elevated, whereas they were hardly detectable in wild types. In human carotid atherectomies and arteriosclerotic coronary arteries, immunohistochemical analysis revealed expression of CYR61 within connective tissue in neointima, adventitia, and surrounding small capillaries and blood vessels, colocalized with ACE and Ang II. Normal human arteries showed no significant staining for CYR61. Conclusions — CYR61, an angiogenic factor, is induced by Ang II in vascular cells and tissue. The expression of CYR61, colocalized with Ang II and ACE, in small vessels of human arteriosclerotic lesions is consistent with the notion that the activated renin-angiotensin system may contribute to plaque neovascularization by enhancing regulators of microvessel formation and cell proliferation.
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CCN1 is overexpressed in vascular smooth muscle cells of atherosclerotic lesions and in the neointima of restenosis after balloon angioplasty, in rodent models and humans.
“CCN1 is overexpressed in vascular smooth muscle cells of atherosclerotic lesions and in the neointima of restenosis after balloon angioplasty, both in rodent models and in humans [23,56,58,135].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [23]
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References 33 · Cited by 114
Research works printed but not linked: 1
- Andrade SP, Cardoso CC, Machado RD, et al. Angiotensin-II-induced angiogenesis in sponge implants in mice. Int J Microcirc Clin Exp. 1996;16:302-307.
- Authors
- Hilfiker, A., Hilfiker-Kleiner, D., Fuchs, M., Kaminski, K., Lichtenberg, A., Rothkötter, H.-J., Schieffer, B., & Drexler, H.
- Affiliations
- Medizinische Hochschule Hannover (DE)
- From the Department of Cardiology and Angiology (A.H., D.H.-K., M.F., K.K., B.S., H.D.), Department of Cardiovascular Surgery (A.L.), and Center of Anatomy (H.-J.R.), Medizinische Hochschule Hannover, Germany.
- Venue
- Circulation
- Published
- 2002-07-09
- Volume
- 106
- Issue
- 2
- Pages
- 254-260
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2149485678
- Cited by
- 114
- References
- 33
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 3 · 2021: 6 · 2020: 4 · 2019: 5 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 5 · 2013: 3
- FWCI
- 6.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- CYR61, angiotensin II, arteriosclerosis, renin-angiotensin system, angiotensin II type 1 receptor, smooth muscle cells, plaque neovascularization, ApoE-deficient mice, carotid atherosclerosis, coronary artery disease, angiotensin-converting enzyme, gene expression regulation
- MeSH terms
- Angiotensin II, Animals, Aorta, Apolipoproteins E, Arteriosclerosis, Blood Vessels, Cells, Cultured, Growth Substances, Humans, Mice, Inbred C57BL, Muscle, Smooth, Vascular, Receptors, Angiotensin, RNA, Messenger, Transcriptional Activation, Up-Regulation, Immediate-Early Proteins, Mice, Knockout, Intercellular Signaling Peptides and Proteins, Angiogenesis Inducing Agents, Receptor, Angiotensin, Type 1, Mice, Rats, Cysteine-Rich Protein 61
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