title: Fenofibrate and extended-release niacin improve the endothelial protective effects of HDL in patients with metabolic syndrome.
abstract: BACKGROUND
  Fibrates and niacin are at present the most effective therapies to increase plasma levels of high density lipoprotein-cholesterol (HDL-C); to date, limited data are available on their effects on HDL protective functions.
  
  
  RESULTS
  Within a multicenter, randomized, open-label, cross-over study, 37 patients with metabolic syndrome received 6weeks' treatment with fenofibrate or extended-release niacin (ER niacin), with a 4weeks' wash-out period. HDL ability to preserve endothelial cell homeostasis was assessed by incubating cultured endothelial cells with HDL isolated from patients at baseline and after each treatment. HDL isolated from patients at baseline were as effective as control HDL in inhibiting vascular cell adhesion molecule-1 (VCAM-1) expression, but less efficient in promoting endothelial cell nitric oxide (NO) release. Both fenofibrate and ER niacin increased HDL ability to inhibit TNFα-induced VCAM-1 expression (+7% and +11%, respectively). Fenofibrate and ER niacin also improved the impaired HDL ability to induce the expression of endothelial nitric oxide synthase and NO production (+10% and +8%, respectively). Interestingly, HDL isolated after treatment showed an ability to promote endothelial NO release similar to HDL isolated from controls. No differences were observed between the two drugs. With both drugs, HDL function was improved irrespective of baseline HDL-C levels.
  
  
  CONCLUSIONS
  Treatment with fenofibrate or ER niacin in patients with metabolic syndrome not only increased HDL-C levels but also improved the endothelial protective effects of HDL.
authors.affiliation: Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Gomaraschi
authors.affiliation: Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Ossoli
authors.affiliation: Department of Pharmacy, University of Parma, Parma, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Adorni
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Damonte
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Eric
authors.initials: E
authors.lastname: Niesor
authors.affiliation: IRCCS Cardiologico Monzino, Milano, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Veglia
authors.affiliation: Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Franceschini
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Renee
authors.initials: R
authors.lastname: Benghozi
authors.affiliation: Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy. Electronic address: laura.calabresi@unimi.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Calabresi
mesh_terms: D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000097:blood*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000627:therapeutic use*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D009525:Niacin / Q000627:therapeutic use*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D020011:Protective Agents / Q000627:therapeutic use*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D008076:Cholesterol, HDL; D003692:Delayed-Action Preparations; D000960:Hypolipidemic Agents; D020011:Protective Agents; D019010:Vascular Cell Adhesion Molecule-1; D009525:Niacin; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D011345:Fenofibrate
keywords: Endothelial cells; Fenofibrate; High density lipoprotein; Niacin; Nitric oxide