title: Protective role of oleic acid against cardiovascular insulin resistance and in the early and late cellular atherosclerotic process.
abstract: BACKGROUND
  Several translational studies have identified the differential role between saturated and unsaturated fatty acids at cardiovascular level. However, the molecular mechanisms that support the protective role of oleate in cardiovascular cells are poorly known. For these reasons, we studied the protective role of oleate in the insulin resistance and in the atherosclerotic process at cellular level such as in cardiomyocytes (CMs), vascular smooth muscle cells (VSMCs) and endothelial cells (ECs).
  
  
  METHODS
  The effect of oleate in the cardiovascular insulin resistance, vascular dysfunction, inflammation, proliferation and apoptosis of VSMCs were analyzed by Western blot, qRT-PCR, BrdU incorporation and cell cycle analysis.
  
  
  RESULTS
  Palmitate induced insulin resistance. However, oleate not only did not induce cardiovascular insulin resistance but also had a protective effect against insulin resistance induced by palmitate or TNFα. One mechanism involved might be the prevention by oleate of JNK-1/2 or NF-κB activation in response to TNF-α or palmitate. Oleate reduced MCP-1 and ICAM-1 and increased eNOS expression induced by proinflammatory cytokines in ECs. Furthermore, oleate impaired the proliferation induced by TNF-α, angiotensin II or palmitate and the apoptosis induced by TNF-α or thapsigargin in VSMCs.
  
  
  CONCLUSIONS
  Our data suggest a differential role between oleate and palmitate and support the concept of the cardioprotector role of oleate as the main lipid component of virgin olive oil. Thus, oleate protects against cardiovascular insulin resistance, improves endothelial dysfunction in response to proinflammatory signals and finally, reduces proliferation and apoptosis in VSMCs that may contribute to an ameliorated atherosclerotic process and plaque stability.
authors.affiliation: Biochemistry and Molecular Biology Department, School of Pharmacy, Complutense University of Madrid, Madrid, Spain.|Health Research Institute of San Carlos Clinic Hospital (IdISSC), Madrid, Spain.|CIBER of Diabetes and Associated Metabolic Diseases, Madrid, Spain.
authors.forename: Liliana
authors.initials: L
authors.lastname: Perdomo
authors.affiliation: Biochemistry and Molecular Biology Department, School of Pharmacy, Complutense University of Madrid, Madrid, Spain.|Health Research Institute of San Carlos Clinic Hospital (IdISSC), Madrid, Spain.|CIBER of Diabetes and Associated Metabolic Diseases, Madrid, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Beneit
authors.affiliation: Biochemistry and Molecular Biology Department, School of Pharmacy, Complutense University of Madrid, Madrid, Spain.|Health Research Institute of San Carlos Clinic Hospital (IdISSC), Madrid, Spain.|CIBER of Diabetes and Associated Metabolic Diseases, Madrid, Spain.
authors.forename: Yolanda F
authors.initials: YF
authors.lastname: Otero
authors.affiliation: Biochemistry and Molecular Biology Department, School of Pharmacy, Complutense University of Madrid, Madrid, Spain.|Health Research Institute of San Carlos Clinic Hospital (IdISSC), Madrid, Spain.|CIBER of Diabetes and Associated Metabolic Diseases, Madrid, Spain.
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Escribano
authors.affiliation: Biochemistry and Molecular Biology Department, School of Pharmacy, Complutense University of Madrid, Madrid, Spain.|Health Research Institute of San Carlos Clinic Hospital (IdISSC), Madrid, Spain.|CIBER of Diabetes and Associated Metabolic Diseases, Madrid, Spain.
authors.forename: Sabela
authors.initials: S
authors.lastname: Díaz-Castroverde
authors.affiliation: Biochemistry and Molecular Biology Department, School of Pharmacy, Complutense University of Madrid, Madrid, Spain. algomezh@ucm.es.|Health Research Institute of San Carlos Clinic Hospital (IdISSC), Madrid, Spain. algomezh@ucm.es.|CIBER of Diabetes and Associated Metabolic Diseases, Madrid, Spain. algomezh@ucm.es.
authors.forename: Almudena
authors.initials: A
authors.lastname: Gómez-Hernández
authors.affiliation: Biochemistry and Molecular Biology Department, School of Pharmacy, Complutense University of Madrid, Madrid, Spain.|Health Research Institute of San Carlos Clinic Hospital (IdISSC), Madrid, Spain.|CIBER of Diabetes and Associated Metabolic Diseases, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Benito
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D007249:Inflammation; D007333:Insulin Resistance; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology*; D010168:Palmitates / Q000494:pharmacology; D019308:Palmitic Acid / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C090509:Icam1 protein, mouse; D016328:NF-kappa B; D010168:Palmitates; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D018799:Intercellular Adhesion Molecule-1; D019301:Oleic Acid; D019308:Palmitic Acid; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse