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

Abstract

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.

Effect of Stanozolol and/or Cannabis Abuse on Hypertrophic Mechanism and Oxidative Stress of Male Albino Rat Cardiac Tissue in Relation to Exercise: A Sport Abuse Practice

“…Furthermore, cannabinoid receptors are G-protein coupled receptors that influence the connected other pathways MAPK, ERK. The cannabis active components caused an upregulation in phosphorylation of AKT and ERK1/2 through G-protein coupled receptor activation [ 55 ]. In addition, oxidative stress is exaggerated in such conditions.…”

Special Issue: Therapeutic Potential for Cannabis and Cannabinoids

“…Golan and colleagues found that a novel compound (HU-585), a synthetic derivative of anandamide and oleic acid, induces apoptosis and senescence in treatment-resistant neuroblastoma cells [ 15 ]. Greiner et al report that activation of the cannabinoid receptor 2 produces protective effects in vascular smooth muscle cells and cardiac myocytes, and the opposite effect is observed when cannabinoid receptor 1 is activated in these cells [ 16 ]. Finally, in a study by Mottarlini and colleagues, it was found that cannabidiol administered via intraperitoneal injection is able to be detected in the prefrontal cortex of the brain, and that CBD treatment modulates the expression of brain-derived neurotropic factor (BDNF) [ 17 ].…”