THE ROLE OF HORMONAL EFFECTS AND THE ENDOCANNABINOID SYSTEM IN CARDIOVASCULAR ADAPTATION PROCESSES
Vass Zsolt
Health Sciences
Dr. Nagy Zoltán Zsolt
SE ETK Szél Éva terem
2025-08-29 14:00:00
Theoretical and preclinical health sciences
Dr. Lenti Katalin
Bednárikné Dr. Dörnyei Gabriella és Dr. Szekeres Mária
Dr. Kocsis László Lajos
Dr. Módos Dezső
Dr. Balogh Zoltán
Dr. Mák Erzsébet
Dr. Kanizsai Péter
the first project we aimed to understand the impact of the ECS and CB1 receptor
activation on vascular functions and to test the impact of the missing receptor function.
Also to reveal any potential interplay between the ECS and the female estrogen status on
the vascular remodeling using CB1R wild-type and knockout female mice. We found that
the levels of conjugated E2 were elevated in CB1R knockout mice, compared to their
wild-type counterparts. In CB1R knockout mice, an enhanced vasodilation to Ach and E2
was found, which was attenuated by NOS inhibition. Inhibition of cyclooxygenase
decreased phenylephrine-induced vasoconstriction, while it increased acetylcholinevasodilation
in WT mice. This effect wasn’t observed in the CB1R-KO group. Effects of
indomethacin on E2-relaxation in CB1R-KO mice became opposite to those observed in
WT. CB1R knockout female mice represented by better vasodilation responses to be
realized by augmented nitric oxide pathway and by a decreased effect of constrictor
prostanoids. (Bányai, Vass, et al., 2023)
Related to the second part of the experiments, we examined the potential role and
mechanism of CB1Rs in the hypercholesterolemia-induced remodeling of vascular wall
by using our novel developed double-knockout, LDLR-KO and CB1R-KO AS-prone
mouse model kept on high-fat or control diets for 5 months. We investigated the impact
of the presence of CB1R on the hypercholesterolemia-induced functional and structural
remodeling of the aortic wall. High-fat diet elevated the cholesterol levels in the LDLRKO
mice into serious patophysiological ranges, which were significantly higher than in
the LDLR wild-type mice. Cholesterol levels were not influenced by CB1Rs. Achinduced
relaxation was depressed to HFD, which was moderated by the absence of
CB1Rs. The BP values were elevated in LDLR knockout animals compared to their WT
counterparts, which was significantly higher in HFD groups (p<0.05), however, this
elevation to HFD was attenuated in CB1R knockout mice. A depressed eNOS expression
was found in the HFD, WT mice compared to CD group, which was enhanced in CB1RKO
groups. Our findings suggest that deletion of the CB1R gene significantly attenuates
vascular damage in hypercholesterolemic mice. (Vass et al., 2024) We can conclude that
in some cases newly designed selective CB1R inhibitors might have pharmatherapeutic
benefits in the future in the treatment of hypercholesterolemia and AS.
