Expression of Interleukin-6 in Atherosclerotic Lesions of Male ApoE-Knockout Mice

Abstract

Abstract-Increased levels of interleukin-6 (IL-6) have been proposed to contribute to a number of pathological disorders, including osteoporosis and Alzheimer's disease. In human atherosclerotic lesions, IL-6 protein and mRNA have been detected, although the role of IL-6 in plaque formation is unknown. We have examined the expression pattern of IL-6 mRNA and secreted protein in male apolipoprotein E-knockout (apoE-KO) mice aortas. Furthermore, we have evaluated the effects of 17␤-estradiol (E2), a vasculoprotective sex steroid hormone, on the secretion of this inflammatory cytokine from isolated male apoE-KO mice aortas. The expression of IL-6 mRNA was detected by reverse transcription-polymerase chain reaction in the apoE-KO mouse aortas but not in the aortas of age-matched control mice. Similarly, the secretion of IL-6 protein from isolated apoE-KO aortic segments was significantly greater than that from aortas of age-matched control animals. The secretion of IL-6 from isolated aortic rings of apoE-KO mice ranging in age from 6 to 48 weeks showed a significant, positive correlation with percent lesion area measured in the same tissue.Immunohistochemical staining of apoE-KO mouse aortic tissue sections demonstrated colocalization of IL-6 expression with macrophages. Treatment of male apoE-KO mice with E2 for 3 weeks resulted in a statistically significant 50% reduction in IL-6 secretion from ex vivo aortic tissue segments. There was no significant change in total serum cholesterol and triglyceride levels in the E2-treated group compared with placebo-treated controls. These data demonstrate that (1) IL-6 mRNA and protein are expressed in the atherosclerotic plaques of apoE-KO mice aortas and (2) IL-6 production is suppressed by E2 treatment, which may contribute to the antiatherosclerotic effects of E2 in the apoE-KO mouse model of atherosclerosis. (Arterioscler Thromb Vasc Biol. 1998;18:1498-1505.)

Angiotensin II Increases Urokinase-Type Plasminogen Activator Expression and Induces Aneurysm in the Abdominal Aorta of Apolipoprotein E-Deficient Mice

“…8 -10 IL-6 is increased in atherosclerotic lesions in apoE-KO mice in association with the infiltrating macrophages. 11 In human AAAs, the circulating level of IL-6 has been reported to be elevated 12 and positively correlated with aortic diameter expansion. 13 Consistent with these observations, we showed that ex vivo secretion of IL-6 from the aneurysmal segment of the aorta was increased compared to the aortic arch in Ang II-treated mice and to the aortic segments from the vehicle-treated mice ( Figure 5).…”

“…The secretion of IL-6 was measured at different time points by using a commercially available murine IL-6 enzyme-linked immunosorbent assay (Biotrak IL-6 ELISA kit; Amersham Life Sciences, Arlington Heights, IL) as described. 11 The IL-6 values were normalized to the weight of the aortic tissue segment and expressed as pg/ml per mg tissue.…”

“…8 -10 IL-6 is a marker of vascular inflammation and it has been shown to increase in atherosclerotic lesions in apoE-KO mice in association with the infiltrating macrophages. 11 In human AAAs, the circulating level of IL-6 has been reported to be elevated 12 and positively correlated with aortic diameter expansion. 13 Therefore, the aim of this study was to test the hypothesis that Ang II promotes vascular inflammation that in turn activates the uPA-plasmin-MMP system, thus causing aneurysm in apoE-KO mice.…”

Stromelysin-1 and Interleukin-6 Gene Promoter Polymorphisms Are Determinants of Asymptomatic Carotid Artery Atherosclerosis

“…37 Studies in apoE knockout mice that develop atherosclerotic plaques in the aorta also show that elevated levels of IL-6 mRNA predominate in the plaque area compared with normal mice. 38 Thus, IL-6 may damage the endothelium and lead to the initiation of atherosclerosis, especially in areas of the vascular system that are predisposed to atherosclerosis because of decreased shear stress with turbulent blood flow such as the carotid bifurcation.…”

The −174 G/C polymorphism of the interleukin-6 gene promoter and essential hypertension in an elderly Italian population

“…25 Studies in ApoE-knockout mice, that spontaneously develop systemic atherosclerosis, also show elevated levels of IL-6 mRNA in the plaque area compared with normal mice. 26 On the other hand, several studies have investigated the possible clinical significance of IL-6 gene variants and analysed their association with atherosclerotic disorders, including carotid atherosclerosis, CAD, and abdominal aortic aneurysm. 25,27,28 Following these observations, our study was designed in order to analyse the association between a common polymorphism of the IL-6 gene promoter and EH.…”