Update on the endocannabinoid-mediated regulation of gelatinase release in arterial wall physiology and atherosclerotic pathophysiology.

Endocannabinoids are endogenous bioactive lipids ubiquitously distributed in several tissues (e.g., brain, adipose tissue, liver, heart and arterial vessels), which play a crucial role in atherosclerosis. Endocannabinoids have been shown to promote cell homeostasis and modulate inflammatory bioactivities mainly via the binding to transmembrane receptors (called cannabinoid type 1 and cannabinoid type 2 receptors, respectively). Although other cannabinoid receptors have been recently identified and shown to play a crucial role in cardiovascular pathophysiology, so far, the pharmacological targeting of both cannabinoid type 1 and cannabinoid type 2 receptors has been described as a promising therapeutic target in atherogenesis and associated inflammatory processes. In particular, endocannabinoids have been shown to modulate the release and activation of matrix degrading enzymes (i.e., matrix metalloproteinases [MMPs]) increasing intraplaque vulnerability. In this article the authors describe the pivotal regulatory activity of the endocannabinoid system on gelatinase (MMP-2 and -9) bioactivity in the arterial wall physiology and pathophysiology.