Beta2-adrenergic activity modulates vascular tone regulation in lecithin:cholesterol acyltransferase knockout mice.

Abstract

Lecithin:cholesterol acyltransferase (LCAT) deficiency is associated with hypoalphalipoproteinemia, generally a predisposing factor for premature coronary heart disease. The evidence of accelerated atherosclerosis in LCAT-deficient subjects is however controversial. In this study, the effect of LCAT deficiency on vascular tone and endothelial function was investigated in LCAT knockout mice, which reproduce the human lipoprotein phenotype. Aortas from wild-type (Lcat(wt)) and LCAT knockout (Lcat(KO)) mice exposed to noradrenaline showed reduced contractility in Lcat(KO) mice (P<0.005), whereas acetylcholine exposure showed a lower NO-dependent relaxation in Lcat(KO) mice (P<0.05). Quantitative PCR and Western blotting analyses suggested an adequate eNOS expression in Lcat(KO) mouse aortas. Real-time PCR analysis indicated increased expression of β2-adrenergic receptors vs wild-type mice. Aorta stimulation with noradrenaline in the presence of propranolol, to abolish the β-mediated relaxation, showed the same contractile response in the two mouse lines. Furthermore, propranolol pretreatment of mouse aortas exposed to L-NAME prevented the difference in responses between Lcat(wt) and Lcat(KO) mice. The results indicate that LCAT deficiency leads to increased β2-adrenergic relaxation and to a consequently decreased NO-mediated vasodilation that can be reversed to guarantee a correct vascular tone. The present study suggests that LCAT deficiency is not associated with an impaired vascular reactivity.

• Authors: S Manzini, C Pinna, M Busnelli, P Cinquanta, E Rigamonti, G S Ganzetti, F Dellera, A Sala, L Calabresi, G Franceschini, C Parolini, G Chiesa
• Journal: Vascular pharmacology (Vascul Pharmacol) Vol. 74 Pg. 114-121 (Nov 2015) ISSN: 1879-3649 [Electronic] United States
• PMID: 26254103 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015. Published by Elsevier Inc.

Chemical References

• Adrenergic Agents
• Lecithins
• Receptors, Adrenergic, beta-2
• Nitric Oxide
• Nitric Oxide Synthase Type III
• Phosphatidylcholine-Sterol O-Acyltransferase

Topics

• Adrenergic Agents (pharmacology)
• Animals
• Aorta (drug effects, metabolism)
• Lecithin Cholesterol Acyltransferase Deficiency (drug therapy, metabolism)
• Lecithins (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type III (metabolism)
• Phosphatidylcholine-Sterol O-Acyltransferase (metabolism)
• Receptors, Adrenergic, beta-2 (metabolism)
• Vasodilation (drug effects)