Effect of leptin on vascular calcification in apolipoprotein E-deficient mice.
OBJECTIVE
The adipocytokine leptin has been proposed to increase cardiovascular risk in both obese and diabetic individuals. In the current study, therefore, we used apoE-deficient mice to examine the effects of leptin on both lesion size and calcification.


RESULTS
Mice were treated with once daily intraperitoneal injections of leptin (125 microg/mouse/d) for 2 months. The mice were then euthanized, and sections of the aortic root and thoracic aorta analyzed histomorphometrically. Measurements of lesion size and surface area occupied by atherosclerotic lesions did not reveal any differences between nontreated and leptin-treated animals. However, von Kossa staining of the aortic root demonstrated an 8.3+/-2.0-fold increase in lesion calcification as well as a 2.5+/-0.6-fold increase in valvular calcification in those animals treated with leptin. In addition, the percent total lesion area demonstrating ALP-positive staining was 5.4+/-2.1-fold greater in leptin-treated mice when compared to nontreated control mice. This increase in ALP staining was also accompanied by an increase in the expression of the osteoblast-specific markers, osteocalcin, and osteopontin.


CONCLUSIONS
Based on these observations, we conclude that leptin may increase cardiovascular risk by promoting osteogenic differentiation and thus vascular calcification.
Department of Pathology and Molecular Medicine, McMaster University and Henderson Research Center, Hamilton, Ontario, Canada.
Melec
M
Zeadin
Martin
M
Butcher
Geoff
G
Werstuck
Mohammad
M
Khan
Colin K
CK
Yee
Stephen G
SG
Shaughnessy
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001021:Aortic Valve / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D002114:Calcinosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015675:Osteocalcin / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012307:Risk Factors
D001057:Apolipoproteins E; D020738:Leptin; D008055:Lipids; D011994:Recombinant Proteins; C506896:Spp1 protein, mouse; D015675:Osteocalcin; D053495:Osteopontin; D000469:Alkaline Phosphatase