EP3 Receptor Deficiency Improves Vascular Remodeling and Cognitive Impairment in Cerebral Small Vessel Disease
Open accessAbstract
Aging and hypertension are major risk factors for cerebral small vessel disease (CSVD). Anti-hypertensive therapy has achieved effective; however, incomplete results in treating CSVD, suggesting the need for additional treatments. Targeting abnormal inflammatory responses has become a topic of research interest. Small artery remodeling is the main pathological feature of CSVD. Inhibition of the E-prostanoid 3 (EP3) receptor has been shown to attenuate vascular remodeling in peripheral organs; however, little is known about its role in CSVD. Therefore, we investigated whether the deletion of EP3 attenuates the development of CSVD in an animal model-- stroke-prone renovascular hypertensive rat (RHRsp). We found that the cerebral small arteries of RHRsp exhibited increased EP3 expression. Despite no alleviation of hypertension, the deletion of EP3 still attenuated the cerebral small artery remodeling of RHRsp, as evidenced by reduced overexpression of extracellular matrix (ECM) in the vessel. In vitro experiments indicated that EP3 deletion regulated the expression of ECM by downregulating TGF-β1/Smad signaling. Furthermore, the Morris water maze test and magnetic resonance test demonstrated that EP3 knockout attenuated cognitive impairment of the RHRsp, possibly through increased cerebral blood flow. Together, our results indicate that the deletion of EP3 attenuates vascular remodeling and vascular cognitive impairment induced by hypertension, and blockade of the EP3 receptor may be a promising strategy for the treatment of CSVD.
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Liu, H., Huang, Z., Deng, B., Chang, Z., Yang, X., Guo, X., Yuan, F., Yang, Q., Wang, L., Zou, H., et al. (2023) · Aging and disease · doi:10.14336/ad.2022.0514 · Cited by 20 · see citing works
- Authors
- Liu, N., Tang, J., Xue, Y., Mok, V., Zhang, M., Ren, X., Wang, Y., & Fu, J.
- Affiliations
- Fudan University (CN)
- Chinese University of Hong Kong (HK)
- Capital Medical University (CN)
- Corresponding author
- Wang, Yilong
- Fu, Jianhui
- ORCID
- Mok, Vincent
- Venue
- Aging and disease
- Publisher
- Aging and Disease
- Published
- 2022
- Volume
- 13
- Issue
- 1
- Pages
- 313
- ISSN
- 2152-5250 (ISSN-L)
- PMC
- PMC8782563
- OpenAlex
- W4206994361
- Cited by
- 15
- References
- 52
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 1 · 2022: 1
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Aging and Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81901179, 81671151)
- Science and Technology Commission of Shanghai Municipality
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- EP3 receptor, cerebral small vessel disease, vascular remodeling, cognitive impairment, hypertension, extracellular matrix, TGF-β1/Smad signaling, cerebral blood flow, receptor knockout
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