Summary: | Cannabinoids (CB) are implicated in cardiovascular diseases via the two main receptor subtypes CB<sub>1</sub>R and CB<sub>2</sub>R. 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 CB<sub>1</sub>- and CB<sub>2</sub> 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)—CB<sub>1</sub>R agonist, rimonabant—CB<sub>1</sub>R antagonist, John W. Huffman (JWH133)—CB<sub>2</sub>R agonist and CB<sub>2</sub>R antagonist—6-Iodopravadoline (AM630). Treatment of cells with the CB<sub>2</sub>R 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. CB<sub>1</sub>R inhibition with rimonabant showed similar protective properties as the CB<sub>2</sub>R agonist JWH133, but to a lesser extent. In conclusion, CB<sub>1</sub>R and CB<sub>2</sub>R exert opposite effects on cell glucose uptake, proteolysis and apoptosis in both VSMCs and H9c2 cells. The CB<sub>2</sub>R 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.
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