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 (Lcatwt) and LCAT knockout (LcatKO) mice exposed to noradrenaline showed reduced contractility in LcatKO mice (P<0.005), whereas acetylcholine exposure showed a lower NO-dependent relaxation in LcatKO mice (P<0.05). Quantitative PCR and Western blotting analyses suggested an adequate eNOS expression in LcatKO 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 Lcatwt and LcatKO 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.

Beta2-adrenergic activity modulates vascular tone regulation in lecithin : cholesterol acyltransferase knockout mice / 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. - In: VASCULAR PHARMACOLOGY. - ISSN 1537-1891. - 74(2015 Nov), pp. 114-121. [10.1016/j.vph.2015.08.006]

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

S. Manzini
Primo
;
C. Pinna
Secondo
;
M. Busnelli;P. Cinquanta;E. Rigamonti;G.S. Ganzetti;F. Dellera;A. Sala;L. Calabresi;G. Franceschini;C. Parolini
Penultimo
;
G. Chiesa
Ultimo
2015-11

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 (Lcatwt) and LCAT knockout (LcatKO) mice exposed to noradrenaline showed reduced contractility in LcatKO mice (P<0.005), whereas acetylcholine exposure showed a lower NO-dependent relaxation in LcatKO mice (P<0.05). Quantitative PCR and Western blotting analyses suggested an adequate eNOS expression in LcatKO 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 Lcatwt and LcatKO 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.
adrenergic receptors; aorta; endothelial NO synthase; lecithin:cholesterol acyltransferase; mouse model; pharmacology; molecular medicine; physiology
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/343442
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