4.7 Article

Differential Regulation of MMPs, Apoptosis and Cell Proliferation by the Cannabinoid Receptors CB1 and CB2 in Vascular Smooth Muscle Cells and Cardiac Myocytes

Journal

BIOMEDICINES
Volume 10, Issue 12, Pages -

Publisher

MDPI
DOI: 10.3390/biomedicines10123271

Keywords

cannabinoid receptors; MMP-2; MMP-9; VSMC; H9c2 cells; glucose; cell proliferation; apoptosis; cardiovascular disease

Funding

  1. Charite Universitatsmedizin Berlin, Germany
  2. CARIM-School for Cardiovascular Diseases, Maastricht University, The Netherlands
  3. Charite-Universitatsmedizin Berlin, Institute of Pharmacology, Germany
  4. DZHK
  5. Deutsche Forschungsgemeinschaft [DFG-KI 712/10-1, SFB-1470-A09, DFG-KA 1820/9-1, KA 1820/10-1]
  6. Einstein Foundation/Foundation Charite [EVF-BIH-2018-440]

Ask authors/readers for more resources

Cannabinoids regulate cell glucose uptake, proteolysis, and apoptosis through CB1R and CB2R receptors. The CB2R agonist JWH133 shows the highest protective properties.
Cannabinoids (CB) are implicated in cardiovascular diseases via the two main receptor subtypes CB1R and CB2R. This study investigated whether cannabinoids regulate the activity of matrix metalloproteases (MMP-2, MMP-9) in vascular smooth muscle cells (VSMCs) and in cells of cardiac origin (H9c2 cell line). The influence of CB1- and CB2 receptor stimulation or inhibition on cell proliferation, apoptosis and glucose uptake was also evaluated. We used four compounds that activate or block CB receptors: arachidonyl-2-chloroethylamide (ACEA)-CB1R agonist, rimonabant-CB1R antagonist, John W. Huffman (JWH133)-CB2R agonist and CB2R antagonist-6-Iodopravadoline (AM630). Treatment of cells with the CB2R agonist JWH133 decreased cytokine activated secretion of proMMP-2, MMP-2 and MMP-9, reduced Fas ligand and caspase-3-mediated apoptosis, normalized the expression of TGF-beta1 and prevented cytokine-induced increase in glucose uptake into the cell. CB1R inhibition with rimonabant showed similar protective properties as the CB2R agonist JWH133, but to a lesser extent. In conclusion, CB1R and CB2R exert opposite effects on cell glucose uptake, proteolysis and apoptosis in both VSMCs and H9c2 cells. The CB2R agonist JWH133 demonstrated the highest protective properties. These findings may pave the way to a new treatment of cardiovascular diseases, especially those associated with extracellular matrix degradation.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available