PhD Scientific Days 2025

Health Sciences II.

Role of CB1 Cannabinoid Receptors in High Fat Diet-Induced Vascular Remodeling in LDL Receptor Knockout Mouse Model of Atherosclerosis

Name of the presenter

Shenker-Horváth Kinga

Institute/workplace of the presenter

Doctoral School of Health Sciences, Semmelweis University, Budapest, Hungary; Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary

Authors

Kinga Shenker-Horváth^1,2,3, Zsolt Vass², Bálint Bányai⁴, Janka Borbála Gém⁴, Kinga Bernadett Kovács⁴, Eszter Mária Horváth⁴, László Hunyady⁴, László Hunyadi⁵, György L. Nádasy⁴, Gabriella Dörnyei², Mária Szekeres^2,4

1: Doctoral School of Health Sciences, Semmelweis University, Budapest, Hungary
2: Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary
3: Center for Sports Nutrition Science, Hungarian University of Sports Science, Budapest, Hungary
4: Department of Physiology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
5: Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary

Text of the abstract

Introduction: LDL receptor knockout (LDLR-KO) mice maintained on a high-fat diet (HFD) develop elevated cholesterol levels and pronounced atherosclerosis (AS). In these animals, vascular dysfunction is linked to structural damage, formation of calcified plaques, and reduced elasticity of the vascular wall. Cannabinoid type 1 receptors (CB1Rs) are known to mediate acute vasodilation, but their role in cardiovascular disease is still controversial.
Aim: We investigated the potential involvement of CB1Rs in vascular function and remodeling in AS-prone LDLR-KO mice.
Method: Experiments were conducted on LDLR and CB1R double knockout (KO) and wild type (WT) mice, kept on HFD or control diet (CD) for 5 months. Blood pressure was assessed using the tail-cuff method. Vascular functions of abdominal aorta rings were tested with wire myography. Vasorelaxation effects of acetylcholine (Ach, 1nM-1µM) were obtained after phenylephrine precontraction, were repeated with inhibitor of nitric oxide synthase (NOS), Nω-nitro-L-arginine. Elastin density was detected with resorcin fuchsin staining.
Results: Blood pressure was higher in LDLR-KO compared to WT mice (systolic/diastolic values: 110/84±5.8/6.8 vs. 102/80±3.3/2.5 mmHg), which was significantly elevated to HFD (118/96±1.9/2 vs. 100/77±3.4/3.1 mmHg, p<0,05) but attenuated in CB1R-KO HFD mice. HFD significantly elevated cholesterol levels in LDLR-KO mice, compared to WT (in average 1039±162 mg/dl vs. 91±18 mg/dl, p<0.05), also total plaque size was significantly increased (from 3.8±3 to 28.3±2%, p<0.05), but these effects were not effectively influenced by the presence of CB1Rs. However, damaged Ach-induced relaxation in HFD animals was moderated in the CB1R-KO. HFD reduced elastin density in LDLR-KO mice (p<0.05), which was reversed in the absence of CB1R. Expression of eNOS was depressed in HFD WT mice compared to CD, which was augmented in CB1R-KO.
Conclusion: Our findings suggest that the absence of CB1Rs significantly reduces vascular damage in AS. These results may support the development of novel therapeutic strategies for cardiovascular diseases through selective modulation of CB1R signaling.
Funding: Supported by the 2024-2.1.1-EKÖP-2024-00004 University Research Scholarship Programme of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund.