HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/2/H904    most recent 00628.2006v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Galili, O. Articles by Lerman, A. Search for Related Content PubMed PubMed Citation Articles by Galili, O. Articles by Lerman, A.

Early experimental obesity is associated with coronary endothelial dysfunction and oxidative stress

Departments of ¹Cardiovascular Diseases, ²Laboratory Medicine and Pathology, and ³Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota

Submitted 13 June 2006 ; accepted in final form 11 September 2006

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.

endothelium; vasodilation; permeability; leptin

This article has been cited by other articles:

				F. Bourgoin, H. Bachelard, M. Badeau, S. Melancon, M. Pitre, R. Lariviere, and A. Nadeau Endothelial and vascular dysfunctions and insulin resistance in rats fed a high-fat, high-sucrose diet Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1044 - H1055. [Abstract] [Full Text] [PDF]

				M.-C. Aubin, C. Lajoie, R. Clement, H. Gosselin, A. Calderone, and L. P. Perrault Female Rats Fed a High-Fat Diet Were Associated with Vascular Dysfunction and Cardiac Fibrosis in the Absence of Overt Obesity and Hyperlipidemia: Therapeutic Potential of Resveratrol J. Pharmacol. Exp. Ther., June 1, 2008; 325(3): 961 - 968. [Abstract] [Full Text] [PDF]

				I. N. Bratz, G. M. Dick, J. D. Tune, J. M. Edwards, Z. P. Neeb, U. D. Dincer, and M. Sturek Impaired capsaicin-induced relaxation of coronary arteries in a porcine model of the metabolic syndrome Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2489 - H2496. [Abstract] [Full Text] [PDF]