ACE Genotype and Endothelium-Dependent Vasodilation of Conduit Arteries and Forearm Microcirculation in Humans

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  • Guido Arcaro
    From the Divisions of Endocrinology and Metabolic Diseases (T.M., A.C., B.B., E.B., M.M., R.C.B.) and of Internal Medicine (G.A., A.L.), Department of Biomedical and Surgical Sciences, University of Verona School of Medicine, and the Laboratory Medicine Unit (M.C., C.C.), Verona City Hospital, Verona, Italy, and the Division of General Medicine (A.S., R.F.), Department of Internal Medicine, University of Ferrara School of Medicine, Ferrara, Italy.
  • Anna Solini
    From the Divisions of Endocrinology and Metabolic Diseases (T.M., A.C., B.B., E.B., M.M., R.C.B.) and of Internal Medicine (G.A., A.L.), Department of Biomedical and Surgical Sciences, University of Verona School of Medicine, and the Laboratory Medicine Unit (M.C., C.C.), Verona City Hospital, Verona, Italy, and the Division of General Medicine (A.S., R.F.), Department of Internal Medicine, University of Ferrara School of Medicine, Ferrara, Italy.
  • Tiziano Monauni
    From the Divisions of Endocrinology and Metabolic Diseases (T.M., A.C., B.B., E.B., M.M., R.C.B.) and of Internal Medicine (G.A., A.L.), Department of Biomedical and Surgical Sciences, University of Verona School of Medicine, and the Laboratory Medicine Unit (M.C., C.C.), Verona City Hospital, Verona, Italy, and the Division of General Medicine (A.S., R.F.), Department of Internal Medicine, University of Ferrara School of Medicine, Ferrara, Italy.
  • Anna Cretti
    From the Divisions of Endocrinology and Metabolic Diseases (T.M., A.C., B.B., E.B., M.M., R.C.B.) and of Internal Medicine (G.A., A.L.), Department of Biomedical and Surgical Sciences, University of Verona School of Medicine, and the Laboratory Medicine Unit (M.C., C.C.), Verona City Hospital, Verona, Italy, and the Division of General Medicine (A.S., R.F.), Department of Internal Medicine, University of Ferrara School of Medicine, Ferrara, Italy.
  • Barbara Brunato
    From the Divisions of Endocrinology and Metabolic Diseases (T.M., A.C., B.B., E.B., M.M., R.C.B.) and of Internal Medicine (G.A., A.L.), Department of Biomedical and Surgical Sciences, University of Verona School of Medicine, and the Laboratory Medicine Unit (M.C., C.C.), Verona City Hospital, Verona, Italy, and the Division of General Medicine (A.S., R.F.), Department of Internal Medicine, University of Ferrara School of Medicine, Ferrara, Italy.
  • Alessandro Lechi
    From the Divisions of Endocrinology and Metabolic Diseases (T.M., A.C., B.B., E.B., M.M., R.C.B.) and of Internal Medicine (G.A., A.L.), Department of Biomedical and Surgical Sciences, University of Verona School of Medicine, and the Laboratory Medicine Unit (M.C., C.C.), Verona City Hospital, Verona, Italy, and the Division of General Medicine (A.S., R.F.), Department of Internal Medicine, University of Ferrara School of Medicine, Ferrara, Italy.
  • Renato Fellin
    From the Divisions of Endocrinology and Metabolic Diseases (T.M., A.C., B.B., E.B., M.M., R.C.B.) and of Internal Medicine (G.A., A.L.), Department of Biomedical and Surgical Sciences, University of Verona School of Medicine, and the Laboratory Medicine Unit (M.C., C.C.), Verona City Hospital, Verona, Italy, and the Division of General Medicine (A.S., R.F.), Department of Internal Medicine, University of Ferrara School of Medicine, Ferrara, Italy.
  • Marco Caputo
    From the Divisions of Endocrinology and Metabolic Diseases (T.M., A.C., B.B., E.B., M.M., R.C.B.) and of Internal Medicine (G.A., A.L.), Department of Biomedical and Surgical Sciences, University of Verona School of Medicine, and the Laboratory Medicine Unit (M.C., C.C.), Verona City Hospital, Verona, Italy, and the Division of General Medicine (A.S., R.F.), Department of Internal Medicine, University of Ferrara School of Medicine, Ferrara, Italy.
  • Claudio Cocco
    From the Divisions of Endocrinology and Metabolic Diseases (T.M., A.C., B.B., E.B., M.M., R.C.B.) and of Internal Medicine (G.A., A.L.), Department of Biomedical and Surgical Sciences, University of Verona School of Medicine, and the Laboratory Medicine Unit (M.C., C.C.), Verona City Hospital, Verona, Italy, and the Division of General Medicine (A.S., R.F.), Department of Internal Medicine, University of Ferrara School of Medicine, Ferrara, Italy.
  • Enzo Bonora
    From the Divisions of Endocrinology and Metabolic Diseases (T.M., A.C., B.B., E.B., M.M., R.C.B.) and of Internal Medicine (G.A., A.L.), Department of Biomedical and Surgical Sciences, University of Verona School of Medicine, and the Laboratory Medicine Unit (M.C., C.C.), Verona City Hospital, Verona, Italy, and the Division of General Medicine (A.S., R.F.), Department of Internal Medicine, University of Ferrara School of Medicine, Ferrara, Italy.
  • Michele Muggeo
    From the Divisions of Endocrinology and Metabolic Diseases (T.M., A.C., B.B., E.B., M.M., R.C.B.) and of Internal Medicine (G.A., A.L.), Department of Biomedical and Surgical Sciences, University of Verona School of Medicine, and the Laboratory Medicine Unit (M.C., C.C.), Verona City Hospital, Verona, Italy, and the Division of General Medicine (A.S., R.F.), Department of Internal Medicine, University of Ferrara School of Medicine, Ferrara, Italy.
  • Riccardo C. Bonadonna
    From the Divisions of Endocrinology and Metabolic Diseases (T.M., A.C., B.B., E.B., M.M., R.C.B.) and of Internal Medicine (G.A., A.L.), Department of Biomedical and Surgical Sciences, University of Verona School of Medicine, and the Laboratory Medicine Unit (M.C., C.C.), Verona City Hospital, Verona, Italy, and the Division of General Medicine (A.S., R.F.), Department of Internal Medicine, University of Ferrara School of Medicine, Ferrara, Italy.

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Abstract

<jats:p> The ACE gene is a candidate gene for cardiovascular disease. Endothelial dysfunction is considered an intermediate phenotype in the pathogenesis of hypertension and atherosclerosis. We evaluated the role of ACE gene polymorphism in endothelial function of young healthy humans. We assessed ACE genotype (deletion [D]/insertion [I] polymorphism) in 92 young healthy individuals. In 88 of them, endothelium-dependent (flow-mediated) vasodilation and endothelium-independent (nitroglycerin-induced) vasodilation were measured in the common femoral artery and in the brachial (n=84) artery by echo Doppler technique. In 35 subjects, we also applied the forearm perfusion technique to quantify the responses of the forearm vascular bed to 3 increasing doses of 2 endothelium-dependent vasodilators (acetylcholine and bradykinin) and 1 endothelium-independent vasodilator (sodium nitroprusside). The D allele of the ACE gene was associated with a significant blunting (Δ≈26%) of endothelium-dependent vasodilation in the femoral artery ( <jats:italic>P</jats:italic> =0.02) but not in the brachial artery ( <jats:italic>P</jats:italic> =0.55) or in the forearm microcirculation ( <jats:italic>P</jats:italic> =0.70 to 0.80). Endothelium-independent vasodilation was unaffected by the ACE genotype. In young healthy humans, the D allele of the ACE gene is associated with selective endothelial dysfunction of the femoral artery. It remains to be determined whether this association discloses a causal role in vascular, particularly peripheral artery, disease. </jats:p>

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