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

## TL;DR

This study examines how diet and a genetic modification affect blood vessel properties in mice prone to atherosclerosis.

## Contribution

The study reveals how CB1 receptors modulate vascular contractility and structural changes in atherosclerosis-prone mice on a high-fat diet.

## Key findings

- HFD increased Phe-induced contractions similarly across genotypes.
- Double knockout mice showed higher SMA and modified vascular remodeling.
- CB1R absence altered contraction properties and intima/media ratio in HFD groups.

## Abstract

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 < 0.05) similarly in all genotypes. However, contractions were stronger with CD in CB1R-KO compared to WT. Plaque areas were increased in LDLR-KO mice compared to WT, significant in HFD groups (p < 0.05). SMA increased to HFD, while elastin density remained similar, with the highest value in double KO-HFD. Intima/media ratio significantly decreased in double KO-HFD vs. CD. 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.