title: 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.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy. Electronic address: stefano.manzini@gmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Manzini
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy. Electronic address: christian.pinna@unimi.it.
authors.forename: C
authors.initials: C
authors.lastname: Pinna
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy. Electronic address: marco.busnelli@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Busnelli
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy. Electronic address: paola.cinquanta84@gmail.com.
authors.forename: P
authors.initials: P
authors.lastname: Cinquanta
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy. Electronic address: rigamonti.elena@hsr.it.
authors.forename: E
authors.initials: E
authors.lastname: Rigamonti
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy. Electronic address: giuliaganzetti@gmail.com.
authors.forename: G S
authors.initials: GS
authors.lastname: Ganzetti
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy. Electronic address: dellera.federica@gmail.com.
authors.forename: F
authors.initials: F
authors.lastname: Dellera
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy; Institute of Biomedicine and Molecular Immunology, CNR, Palermo, Italy. Electronic address: angelo.sala@unimi.it.
authors.forename: A
authors.initials: A
authors.lastname: Sala
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy. Electronic address: laura.calabresi@unimi.it.
authors.forename: L
authors.initials: L
authors.lastname: Calabresi
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy. Electronic address: guido.franceschini@unimi.it.
authors.forename: G
authors.initials: G
authors.lastname: Franceschini
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy. Electronic address: cinzia.parolini@unimi.it.
authors.forename: C
authors.initials: C
authors.lastname: Parolini
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy. Electronic address: Giulia.Chiesa@unimi.it.
authors.forename: G
authors.initials: G
authors.lastname: Chiesa
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D007863:Lecithin Cholesterol Acyltransferase Deficiency / Q000188:drug therapy* / Q000378:metabolism*; D054709:Lecithins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
chemical_list: D018663:Adrenergic Agents; D054709:Lecithins; D018343:Receptors, Adrenergic, beta-2; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D007862:Phosphatidylcholine-Sterol O-Acyltransferase
keywords: Adrenergic receptors; Aorta; Endothelial NO synthase; Lecithin:cholesterol acyltransferase; Mouse model