Vascular Contractile and Structural Properties in Diet-Induced Atherosclerosis-Prone CB1-LDL Receptor Double Knockout Animal Model

Background: Atherosclerosis forms the background of several cardiovascular pathologies. LDL receptor knockout (LDLR-KO) mice kept on a high-fat diet (HFD) develop high cholesterol levels. Previously we found that vasodilation responses in HFD LDLR-KO mice were improved in the absence of type 1 cannabinoid receptors (CB1Rs). We aimed to reveal the effects of HFD and CB1Rs on vascular contractile and structural properties. Methods: Experiments were performed on LDLR-CB1R double knockout and wild type (WT) mice, kept on an HFD or control diet (CD) for 5 months. Thoracic aortas were isolated for Oil Red plaque staining and abdominal aorta segments for myography to obtain phenylephrine (Phe)-induced (100 nM-10 µM) contractile responses. Aorta samples were subjected to histology stainings with hematoxylin-eosin and resorcin-fuchsin (elastin density) and for smooth muscle actin (SMA) immunohistochemistry. Results: Phe-induced contractions significantly increased in HFD groups (p 1R-KO compared to WT. Plaque areas were increased in LDLR-KO mice compared to WT, significant in HFD groups (p Conclusions: Our results indicate that HFD-treated LDLR-KO mice develop atherosclerosis with functional contractile and structural alterations modulated by CB1Rs: absence of CB1Rs elicited higher contraction properties with some modification in vascular remodeling indicating contribution of the CB1R to cellular signalization controlling wall thickness and elasticity in pathological conditions.