P.29 Involvement of Cannabinoid Receptors in Regulation of MMPs, Cell Proliferation and Apoptosis in Vascular Smooth Muscle Cells
- 10.2991/artres.k.201209.042How to use a DOI?
- MMPs VSMC cannbinoid receptors
Objectives: Cannabinoid receptors CB1R and CB2R are expressed in the vascular smooth muscle cells (VSMCs) and may contribute to vascular remodeling process (O’Sullivan, 2015). This study aimed to investigate the implication of CB1R and CB2R in the regulation of matrix metalloproteases MMP2 and MMP9, cell proliferation and apoptosis.
Methods: Primary VSMCs of contractile type were derived from rat aorta. Following compounds were studied: the CB1R agonist arachidonyl-2-chloroethylamide (ACEA), the CB1R antagonist/inverse agonist rimonabant, the CB2R agonist JWH133, the CB2R antagonist/inverse agonist AM630. The cells were treated with compounds simultaneously with IL1α stimulation. MMP2 and MMP9 were analyzed 48h after treatment via gelatin zymography, Western blotting and immunofluorescence. Apoptotic markers FasL, Caspase-3 and TGFbeta1 were used. This experimental setup was repeated using IncuCyte cell imaging to evaluate cell proliferation and apoptosis.
Results: The CB2R agonist JWH133 decreased the activity of proMMP9 (p < 0.05), abolished IL1α -induced up-regulation of proMMP9/MMP9 proteins, and decreased MMP2 activity by tendency (11%). JWH133 also decreased the number of apoptotic cells (p < 0.05). Accordingly, CB2R antagonist AM630 did not prevent MMP9 release. CB1R antagonist Rimonabant reduced activity of proMMP9 (35%) and MMP2 (4%) and abolished protein up-regulation of proMMP9/MMP9. CB1R stimulation with ACEA had an ambiguous effect. JWH133 and Rimonabant increased cell proliferation (p < 0,05) and decreased expression of apoptosis markers FasL and caspase-3.
Conclusions: The CB2R agonist JWH133 and CB1R antagonist Rimonabant prevented release of MMP9 and cell death of VSMCs. Therefore, stimulation of the CB2R or blockade of the CB1R may be favorable by vascular outward remodeling processes.
- © 2020 Association for Research into Arterial Structure and Physiology. Publishing services by Atlantis Press International B.V.
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- This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).
Cite this article
TY - JOUR AU - Bettina Greiner AU - Manuela Sommerfeld AU - Ulrich Kintscher AU - Kai Kappert AU - Elena Kaschina PY - 2020 DA - 2020/12/31 TI - P.29 Involvement of Cannabinoid Receptors in Regulation of MMPs, Cell Proliferation and Apoptosis in Vascular Smooth Muscle Cells JO - Artery Research SP - S52 EP - S52 VL - 26 IS - Supplement 1 SN - 1876-4401 UR - https://doi.org/10.2991/artres.k.201209.042 DO - 10.2991/artres.k.201209.042 ID - Greiner2020 ER -