Rapid Development of Vein Graft Atheroma in ApoE-Deficient Mice

Dietrich, Hermann; Hu, Yanhua; Zou, Yiping; Huemer, Ursula; Metzler, Bernhard; Li, Chaohong; Mayr, Manuel; Xu, Qingbo

doi:10.1016/s0002-9440(10)64576-2

Cited by 69 publications

(58 citation statements)

References 40 publications

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“…These groups demonstrated comparable lipid profiles and body weights (Supplemental Table 1). In this model, extent of aortic atherosclerosis and AAA formation and rupture were evaluated (20)(21)(22)(23). In the thoracoabdominal aorta, ApoE-KO mice treated with Ang II developed significantly greater atherosclerotic area compared with that in saline controls (3.4-fold increase, P < 0.01, Ang II versus saline), but concurrent infusion of apelin almost totally blocked this increase (P < 0.001, Ang II plus apelin versus Ang II) ( Figure 1, B and C).…”

Section: Resultsmentioning

confidence: 99%

Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis

Chun¹,

Ali²,

Kojima³

et al. 2008

J. Clin. Invest.

221

269

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Apelin and its cognate G protein-coupled receptor APJ constitute a signaling pathway with a positive inotropic effect on cardiac function and a vasodepressor function in the systemic circulation. The apelin-APJ pathway appears to have opposing physiological roles to the renin-angiotensin system. Here we investigated whether the apelin-APJ pathway can directly antagonize vascular disease-related Ang II actions. In ApoE-KO mice, exogenous Ang II induced atherosclerosis and abdominal aortic aneurysm formation; we found that coinfusion of apelin abrogated these effects. Similarly, apelin treatment rescued Ang II-mediated increases in neointimal formation and vascular remodeling in a vein graft model. NO has previously been implicated in the vasodepressor function of apelin; we found that apelin treatment increased NO bioavailability in ApoE-KO mice. Furthermore, infusion of an NO synthase inhibitor blocked the apelin-mediated decrease in atherosclerosis and aneurysm formation. In rat primary aortic smooth muscle cells, apelin inhibited Ang II-mediated transcriptional regulation of multiple targets as measured by reporter assays. In addition, we demonstrated by coimmunoprecipitation and fluorescence resonance energy transfer analysis that the Ang II and apelin receptors interacted physically. Taken together, these findings indicate that apelin signaling can block Ang II actions in vascular disease by increasing NO production and inhibiting Ang II cellular signaling.

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Section: Resultsmentioning

confidence: 99%

Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis

Chun¹,

Ali²,

Kojima³

et al. 2008

J. Clin. Invest.

221

269

View full text Add to dashboard Cite

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“…The morphological pattern and distribution of various lesion components (lipids, smooth muscle cells, macrophages) in our model were similar to those previously reported. 27 Several clinical studies examining the pathology of veingraft atherosclerosis, risk factors for vein graft atherosclerosis, and therapeutic interventions effective against vein-graft atherosclerosis have generally demonstrated similarities between native and vein-graft atherosclerosis. 28 -30 Similarly, the histomorphometric features of vein-graft atherosclerosis show remarkable similarities to those of native arterial atherosclerosis, 28 and factors such as hyperlipidemia, hypertension, cigarette smoking, and inflammation play critical roles in both disease processes, even though the time course of plaque evolution is accelerated in vein grafts.…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Apolipoprotein A-I–Mimetic Peptide on Evolving and Established Atherosclerosis in Apolipoprotein E-Null Mice

et al. 2004

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Background-Apolipoprotein (apo) A-I and apoA-I-mimetic peptides showed promise to prevent atherosclerosis development. Using a bypassed vein graft model in apoE-null mice, we evaluated the effects of oral or intraperitoneal administration of an apoA-I-mimetic peptide on evolving atherosclerotic lesions in the vein graft and compared such effects on the established atherosclerotic lesions in aortic sinus in the same mice. Methods and Results-We used apoE-null mice in which a segment of inferior vena cava was grafted into the right carotid artery at 16 weeks of age. Native aortic atherosclerotic lesions (established atherosclerosis) and vein-graft atherosclerotic lesions (evolving atherosclerosis) were assessed 4 weeks after daily oral (0.3 mg/mL) or intraperitoneal (50 g in 200 L saline) administration of an apoA-I-mimetic peptide, D4F. Mice receiving saline or water without D4F served as controls. Both oral and intraperitoneal administration of D4F reduced vein-graft atherosclerotic (evolving lesions) plaque size by 43% and 42%, plaque lipid by 70% and 49%, and macrophage immunoreactivity by 63% and 62%, respectively, compared with controls. In contrast, D4F had no effect on the native aortic sinus atherosclerotic lesions (established lesions). Conclusions-Oral and intraperitoneal administration of the apoA-I-mimetic peptide D4F significantly reduced rapidly evolving atherosclerotic lesions in vein grafts but not established atherosclerotic lesions in aortic sinus. These observations suggest that the type of atherosclerotic lesions and the time of initiation during the course of lesion evolution modulate the beneficial effects of apoA-I-mimetic peptides on atherosclerosis.

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“…Hypercholesterolaemia is a risk factor for vein graft failure (Goldman et al 2004), which may be related to adverse effects on endothelial integrity and function (Raja et al 2004). Previously, it has been demonstrated that endothelial regeneration is retarded, and neointima formation is accelerated in vein grafts in hypercholesterolaemic apo E À/À mice compared to normocholesterolaemic controls (Dietrich et al 2000;Xu et al 2003). Topical HDL therapy reduced vein graft atherosclerosis in apo E À/À mice (Feng et al 2011).…”

Section: Hdl and Tissue Repair: Modulation Of Epc Biology Via Sr-bimentioning

confidence: 99%