title: Early experimental obesity is associated with coronary endothelial dysfunction and oxidative stress.
abstract: Obesity is independently associated with increased cardiovascular risk. However, since established obesity clusters with various cardiovascular risk factors, configuring the metabolic syndrome, the early effects of obesity on vascular function are still poorly understood. The current study was designed to evaluate the effect of early obesity on coronary endothelial function in a new animal model of swine obesity. As to method, juvenile domestic crossbred pigs were randomized to either high-fat/high-calorie diet (HF) or normal chow diet for 12 wk. Coronary microvascular permeability and abdominal wall fat were determined by using electron beam computerized tomography. Epicardial endothelial function and oxidative stress were measured in vitro. Systemic oxidative stress, renin-angiotensin activity, leptin levels, and parameters of insulin sensitivity were evaluated. As a result, HF pigs were characterized by abdominal obesity, hypertension, and elevated plasma lysophosphatidylcholine and leptin in the presence of increased insulin sensitivity. Coronary endothelium-dependent vasorelaxation was reduced in HF pigs and myocardial microvascular permeability increased compared with those values in normal pigs. Systemic redox status in HF pigs was similar to that in normal pigs, whereas the coronary endothelium demonstrated higher content of superoxide anions, nitrotyrosine, and NADPH-oxidase subunits, indicating increased tissue oxidative stress. In conclusion, the current study shows that early obesity is characterized by increased vascular oxidative stress and endothelial dysfunction in association with increased levels of leptin and before the development of insulin resistance and systemic oxidative stress. Vascular dysfunction is therefore an early manifestation of obesity and might contribute to the increased cardiovascular risk, independently of insulin resistance.
authors.affiliation: Department of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Offer
authors.initials: O
authors.lastname: Galili
authors.forename: Daniele
authors.initials: D
authors.lastname: Versari
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Sattler
authors.forename: Monica L
authors.initials: ML
authors.lastname: Olson
authors.forename: Dallit
authors.initials: D
authors.lastname: Mannheim
authors.forename: Joseph P
authors.initials: JP
authors.lastname: McConnell
authors.forename: Alejandro R
authors.initials: AR
authors.lastname: Chade
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002199:Capillary Permeability; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D004041:Dietary Fats; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D050152:Intra-Abdominal Fat / Q000473:pathology; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008833:Microcirculation / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D018384:Oxidative Stress; D011897:Random Allocation; D013481:Superoxides / Q000378:metabolism; D013552:Swine; D014057:Tomography, X-Ray Computed; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004041:Dietary Fats; D020738:Leptin; D008055:Lipids; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D013481:Superoxides; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D015237:Dinoprost