Increased expression of adhesion molecules in uremic atherosclerosis in apolipoprotein-E-deficient mice.

Abstract

Chronic renal failure markedly accelerates atherosclerosis in apolipoprotein-E-deficient mice, but the mechanism is unknown. The recruitment of inflammatory cells in the arterial wall by vascular adhesion molecules plays a key role in the formation of classical atherosclerosis. This study examines whether the expression of vascular adhesion molecules is increased in uremic atherosclerosis. Uremia was induced by 5/6 nephrectomy; control mice were sham-operated. After 2 wk of uremia, no lesion formation could be demonstrated in uremic or control mice. After 12 wk, aortas from uremic mice had a 9.8-fold increase of the aortic plaque area fraction compared with control mice (P < 0.0001). The aortic expression of intercellular adhesion molecule-1 (ICAM-1) mRNA in uremic mice was 215 +/- 31% (P < 0.05) and 243 +/- 55% (P < 0.05) of that in controls after 2 and 12 wk, respectively (n = 9 x 4). In contrast, aortic expression of vascular cell adhesion molecule-1 (VCAM-1) mRNA in uremic mice was unchanged after 2 wk but increased to 237 +/- 40% (P < 0.01) of that in control mice after 12 wk. On immunohistochemistry of aortas from uremic mice, ICAM-1 was predominantly present in endothelial cells both in nonlesioned and lesioned aortas, whereas VCAM-1 was predominantly present in the medial smooth muscle cell layer in lesioned aortas. The plasma concentration of soluble ICAM-1 (sICAM-1) (but not of sVCAM-1) was slightly elevated after 2 wk of uremia. In contrast, both sICAM-1 and sVCAM-1 plasma concentrations were markedly higher in uremic than control mice after 12 wk. These results suggest that uremic atherosclerosis is preceded by an upregulation of ICAM-1 expression in arterial endothelium and that formation of early uremic lesions is accompanied by upregulation of VCAM-1 expression in the medial smooth muscle cell layer.

• Authors: Susanne Bro, Flemming Moeller, Claus B Andersen, Klaus Olgaard, Lars B Nielsen
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 15 Issue 6 Pg. 1495-503 (Jun 2004) ISSN: 1046-6673 [Print] United States
• PMID: 15153560 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• DNA, Complementary
• RNA, Messenger
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1

Topics

• Animals
• Aorta (metabolism, pathology)
• Apolipoproteins E (genetics, physiology)
• Arteriosclerosis (pathology)
• Cell Adhesion
• DNA, Complementary (metabolism)
• Immunohistochemistry
• Inflammation
• Intercellular Adhesion Molecule-1 (biosynthesis)
• Male
• Mice
• Myocytes, Smooth Muscle (metabolism)
• Nephrectomy
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Time Factors
• Up-Regulation
• Uremia (pathology)
• Vascular Cell Adhesion Molecule-1 (biosynthesis)