Endogenous cannabinoid receptor CB1 activation promotes vascular smooth-muscle cell proliferation and neointima formation.

Percutaneous transluminal angioplasty is frequently used in patients with severe arterial narrowing due to atherosclerosis. However, it induces severe arterial injury and an inflammatory response leading to restenosis. Here, we studied a potential activation of the endocannabinoid system and the effect of FA amide hydrolase (FAAH) deficiency, the major enzyme responsible for endocannabinoid anandamide degradation, in arterial injury. We performed carotid balloon injury in atherosclerosis-prone apoE knockout (apoE(-/-)) and apoE(-/-)FAAH(-/-) mice. Anandamide levels were systemically elevated in apoE(-/-) mice after balloon injury. ApoE(-/-)FAAH(-/-) mice had significantly higher baseline anandamide levels and enhanced neointima formation compared with apoE(-/-) controls. The latter effect was inhibited by treatment with CB1 antagonist AM281. Similarly, apoE(-/-) mice treated with AM281 had reduced neointimal areas, reduced lesional vascular smooth-muscle cell (SMC) content, and proliferating cell counts. The lesional macrophage content was unchanged. In vitro proliferation rates were significantly reduced in CB1(-/-) SMCs or when treating apoE(-/-) or apoE(-/-)FAAH(-/-) SMCs with AM281. Macrophage in vitro adhesion and migration were marginally affected by CB1 deficiency. Reendothelialization was not inhibited by treatment with AM281. In conclusion, endogenous CB1 activation contributes to vascular SMC proliferation and neointima formation in response to arterial injury.

Association between conventional risk factors and different ultrasound-based markers of atherosclerosis at carotid and femoral levels in a middle-aged population.

Ultrasound detection of sub-clinical atherosclerosis (ATS) may help identify individuals at high cardiovascular risk. Most studies evaluated intima-media thickness (IMT) at carotid level. We compared the relationships between main cardiovascular risk factors (CVRF) and five indicators of ATS (IMT, mean and maximal plaque thickness, mean and maximal plaque area) at both carotid and femoral levels. Ultrasound was performed on 496 participants aged 45-64 years randomly selected from the general population of the Republic of Seychelles. 73.4 % participants had ≥ 1 plaque (IMT thickening ≥ 1.2 mm) at carotid level and 67.5 % at femoral level. Variance (adjusted R2) contributed by age, sex and CVRF (smoking, LDL-cholesterol, HDL-cholesterol, blood pressure, diabetes) in predicting any of the ATS markers was larger at femoral than carotid level. At both carotid and femoral levels, the association between CVRF and ATS was stronger based on plaque-based markers than IMT. Our findings show that the associations between CVRF and ATS markers were stronger at femoral than carotid level, and with plaque-based markers rather than IMT. Pending comparison of these markers using harder cardiovascular endpoints, our findings suggest that markers based on plaque morphology assessed at femoral artery level might be useful cardiovascular risk predictors.