This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (93)  • Contact me when this article is cited  Related Content  • Related letter  • Related article  • Similar articles in JAMA  Topic Collections  • Obesity  • Cardiovascular Disease/ Myocardial Infarction  • Alert me on articles by topic

Peter F. Bodary, PhD; Randal J. Westrick, BS; Kevin J. Wickenheiser; Yuechen Shen, MD; Daniel T. Eitzman, MD

JAMA. 2002;287:1706-1709.

Context  Complications of atherosclerosis are the leading cause of morbidity and mortality in industrialized societies. Obesity has emerged as an independent risk factor for complications of atherosclerotic vascular disease. Leptin, a hormone produced by the adipocyte, increases with obesity and appears to modulate energy balance and food intake. In addition, other actions of leptin have been proposed, including an in vitro effect on platelet aggregation. Thus, the elevated plasma leptin levels in obese individuals may promote vascular thrombosis.

Objective  To test the hypothesis that leptin contributes to in vivo thrombosis via the leptin receptor.

Design and Materials  Between September 2000 and September 2001, a vascular thrombosis model was used to test male 10- to 12-week-old mice completely deficient in leptin or the leptin receptor and mice with platelet leptin-receptor deficiency.

Main Outcome Measure  Time to formation of an occlusive thrombus in the common carotid artery following experimentally induced endothelial injury.

Results  Following onset of vascular injury, wild-type mice (n = 8) formed occlusive thrombosis in a mean (SD) of 42.2 (4.6) minutes, whereas leptin-deficient (n = 5) and leptin receptor–deficient mice (n = 7) formed occlusive thrombosis in 75.2 (10.1) and 68.6 (10.3) minutes, respectively (leptin deficient vs wild-type mice, P = .008; leptin-receptor–deficient vs wild-type, P = .03). When recombinant murine leptin was administered to leptin-deficient mice (n = 4), the time to occlusion was reduced to 41.8 (6.6) minutes (P = .035 vs vehicle control). Following bone marrow transplantation from leptin receptor–deficient (donor) mice to wild-type (recipient) mice, the time to occlusion was prolonged from 22.3 (2.8) minutes in wild-type mice receiving wild-type marrow (n = 3) to 56.8 (5.0) minutes in wild-type mice receiving leptin receptor–deficient bone marrow (n = 5) (P = .003).

Conclusions  Leptin contributes to arterial thrombosis following vascular injury in vivo and these prothrombotic effects appear to be mediated through the platelet leptin receptor.

Author Affiliations: Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor.

RELATED LETTER

Effects of Leptin on Platelet Function in Obese Patients
Francesco Corica, Andrea Corsonello, Francesco Perticone, Peter F. Bodary, and Daniel T. Eitzman
JAMA. 2002;288(3):313-314.
EXTRACT | FULL TEXT  

RELATED ARTICLE

April 3, 2002
JAMA. 2002;287(13):1735-1736.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Leptin Resistance: A Possible Interface of Inflammation and Metabolism in Obesity-Related Cardiovascular Disease
Martin et al.
J Am Coll Cardiol 2008;52:1201-1210.
ABSTRACT | FULL TEXT  

Leptin Enhances the Recruitment of Endothelial Progenitor Cells Into Neointimal Lesions After Vascular Injury by Promoting Integrin-Mediated Adhesion
Schroeter et al.
Circ. Res. 2008;103:536-544.
ABSTRACT | FULL TEXT  

Links Between Adipose Tissue and Thrombosis in the Mouse
Bodary
Arterioscler. Thromb. Vasc. Bio. 2007;27:2284-2291.
ABSTRACT | FULL TEXT  

Sweet and Sticky: Diabetic Platelets, Enhanced Reactivity, and Cardiovascular Risk
Simon and Schmaier
J Am Coll Cardiol 2007;50:1548-1550.
FULL TEXT  

Murine Models of Vascular Thrombosis
Westrick et al.
Arterioscler. Thromb. Vasc. Bio. 2007;27:2079-2093.
ABSTRACT | FULL TEXT  

Adiposity and Cardiovascular Disorders: Disturbance of the Regulatory System Consisting of Humoral and Neuronal Signals
Katagiri et al.
Circ. Res. 2007;101:27-39.
ABSTRACT | FULL TEXT  

Biomarkers of Obesity and Subsequent Cardiovascular Events
Musaad and Haynes
Epidemiol Rev 2007;0:mxm005v1.
ABSTRACT | FULL TEXT  

Admission Plasma Leptin Level Strongly Correlates With the Success of Thrombolytic Therapy in Patients With Acute Myocardial Infarction
Amasyali et al.
ANGIOLOGY 2007;57:671-680.
ABSTRACT  

Leptin Regulates Neointima Formation After Arterial Injury Through Mechanisms Independent of Blood Pressure and the Leptin Receptor/STAT3 Signaling Pathways Involved in Energy Balance
Bodary et al.
Arterioscler. Thromb. Vasc. Bio. 2007;27:70-76.
ABSTRACT | FULL TEXT  

Recombinant Leptin Promotes Atherosclerosis and Thrombosis in Apolipoprotein E-Deficient Mice
Bodary et al.
Arterioscler. Thromb. Vasc. Bio. 2005;25:e119-e122.
ABSTRACT | FULL TEXT  

A rare variant of the leptin gene has large effects on blood pressure and carotid intima-medial thickness: a study of 1428 individuals in 248 families
Gaukrodger et al.
J. Med. Genet. 2005;42:474-478.
ABSTRACT | FULL TEXT  

Homozygosity for Factor V Leiden Leads to Enhanced Thrombosis and Atherosclerosis in Mice
Eitzman et al.
Circulation 2005;111:1822-1825.
ABSTRACT | FULL TEXT  

Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall
Day et al.
Blood 2005;105:192-198.
ABSTRACT | FULL TEXT  

Plasma leptin and prognosis in patients with established coronary atherosclerosis
Wolk et al.
J Am Coll Cardiol 2004;44:1819-1824.
ABSTRACT | FULL TEXT  

Inhibition of Endogenous Leptin Protects Mice From Arterial and Venous Thrombosis
Konstantinides et al.
Arterioscler. Thromb. Vasc. Bio. 2004;24:2196-2201.
ABSTRACT | FULL TEXT  

Leptin, C-Reactive Protein, and Nitric Oxide Production in Healthy Humans * Response
Tsuda et al.
Circulation 2004;110:e330-e330.
FULL TEXT  

Plasma Leptin Levels Are Associated with Coronary Atherosclerosis in Type 2 Diabetes
Reilly et al.
J. Clin. Endocrinol. Metab. 2004;89:3872-3878.
ABSTRACT | FULL TEXT  

Leptin Promotes Vascular Remodeling and Neointimal Growth in Mice
Schafer et al.
Arterioscler. Thromb. Vasc. Bio. 2004;24:112-117.
ABSTRACT | FULL TEXT  

Neointimal Formation After Endovascular Arterial Injury Is Markedly Attenuated in db/db Mice
Stephenson et al.
Arterioscler. Thromb. Vasc. Bio. 2003;23:2027-2033.
ABSTRACT | FULL TEXT  

Strikingly Low Circulating CRP Concentrations in Ultramarathon Runners Independent of Markers of Adiposity: How Low Can You Go?
Tomaszewski et al.
Arterioscler. Thromb. Vasc. Bio. 2003;23:1640-1644.
ABSTRACT | FULL TEXT  

Impaired lung function and serum leptin in men and women with normal body weight: a population based study
Sin and Man
Thorax 2003;58:695-698.
ABSTRACT | FULL TEXT  

Genetic Models in Applied Physiology: Invited Review: Identifying new mouse models of cardiovascular disease: a review of high-throughput screens of mutagenized and inbred strains
Svenson et al.
J. Appl. Physiol. 2003;94:1650-1659.
ABSTRACT | FULL TEXT  

Fabry Disease in Mice Is Associated With Age-Dependent Susceptibility to Vascular Thrombosis
Eitzman et al.
J. Am. Soc. Nephrol. 2003;14:298-302.
ABSTRACT | FULL TEXT  

Effects of Leptin on Platelet Function in Obese Patients
Corica et al.
JAMA 2002;288:313-314.
FULL TEXT  

Uncoupling Metabolism and Coupling Leptin to Cardiovascular Disease
Mark and Sivitz
Arterioscler. Thromb. Vasc. Bio. 2002;22:881-883.
FULL TEXT  

Beginning to Understand Obesity and the Heart
Journal Watch Cardiology 2002;2002:3-3.
FULL TEXT  

Basic Science and Translational Research in JAMA
Fontanarosa and DeAngelis
JAMA 2002;287:1728-1728.
FULL TEXT