Angiotensin II–accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice

Bruemmer, Dennis; Collins, Alan R.; Noh, Grace; Wang, Wei; Territo, Mary; Arias-Magallona, Sarah; Fishbein, Michael C.; Blaschke, Florian; Kintscher, Ulrich; Graf, Kristof; Law, Ronald E.; Hsueh, Willa A.

doi:10.1172/jci200318141

Cited by 248 publications

(132 citation statements)

References 59 publications

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“…Lipid deposition, as determined by Oil Red O staining, was detected in 11.6% [6.1, 14.2] of the area of the aortic arch in the sham surgery group, similar to results from past studies in chow‐fed ApoE −/− mice (Figure 3A and 3B) 6, 22. Chronic RAS resulted in an approximate 3‐fold increase in lipid staining in the aortic arch compared to sham surgery (33.2% [24.4, 47.5] vs 11.6% [6.1, 14.2]; P <0.05).…”

Section: Resultssupporting

confidence: 88%

Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE ^−/− Mice With Unilateral Renal Artery Stenosis

Pathak

Huang

Rojas

et al. 2016

JAHA

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BackgroundChronic unilateral renal artery stenosis (RAS) causes accelerated atherosclerosis in apolipoprotein E–deficient (ApoE−/−) mice, but effects of restoration of renal blood flow on aortic atherosclerosis are unknown.Methods and ResultsMale ApoE−/− mice underwent sham surgery (n=16) or had partial ligation of the right renal artery (n=41) with the ligature being removed 4 days later (D4LR; n=6), 8 days later (D8LR; n=11), or left in place for 90 days (chronic RAS; n=24). Ligature removal at 4 or 8 days resulted in improved renal blood flow, decreased plasma angiotensin II levels, a return of systolic blood pressure to baseline, and increased plasma levels of neutrophil gelatinase associated lipocalin. Chronic RAS resulted in increased lipid staining in the aortic arch (33.2% [24.4, 47.5] vs 11.6% [6.1, 14.2]; P<0.05) and descending thoracic aorta (10.2% [6.4, 25.9] vs 4.9% [2.8, 7.8]; P<0.05), compared to sham surgery. There was an increased amount of aortic arch lipid staining in the D8LR group (22.7% [22.1, 32.7]), compared to sham‐surgery, but less than observed with chronic RAS. Lipid staining in the aortic arch was not increased in the D4LR group, and lipid staining in the descending aorta was not increased in either the D8LR or D4LR groups. There was less macrophage expression in infrarenal aortic atheroma in the D4LR and D8LR groups compared to the chronic RAS group.ConclusionsRestoration of renal blood flow at either 4 or 8 days after unilateral RAS had a beneficial effect on systolic blood pressure, aortic lipid deposition, and atheroma inflammation.

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Section: Resultssupporting

confidence: 88%

Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE ^−/− Mice With Unilateral Renal Artery Stenosis

Pathak

Huang

Rojas

et al. 2016

JAHA

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“…Many in vitro studies also emphasize the importance of an autocrine function for OPN in macrophages, suggesting that macrophages are both a source and a target of OPN . Indeed, macrophages from OPN-null mice were susceptible to programmed cell death and showed impaired macrophage accumulation and migration in response to MCP-1 (Bruemmer et al, 2003). In addition, suppression of OPN production in RAW 264.7 macrophage-like cells impairs their migration, sensitizes them to serum withdrawal-induced cell death, and reduces their secretion of IL-12 (Morimoto et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Osteopontin: Role in immune regulation and stress responses

Wang¹,

Denhardt²

2008

Cytokine & Growth Factor Reviews

597

558

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“…Conversely, the LDL receptor-deficient genotype (LDLR −/− ) develop AS in a diet-dependent manner [19], with more relevant increases in IDL and LDL fractions that are consistent with human familial hypercholesterolemia [18]. In hyperlipidemic mice, A-II infusion induces accelerated AS and aortic aneurysm development dependent on the monocytic chemokines MCP-1 (monocyte chemotactic protein 1) and osteopontin [20][21][22]. These findings strongly implicate the activated monocyte as a major participant in A-II-induced vascular pathology.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II induces IL-6 expression and the Jak-STAT3 pathway in aortic adventitia of LDL receptor-deficient mice

et al. 2007

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Angiotensin II (A-II), the major effector peptide of the renin angiotensin system potently accelerates progression of atherosclerosis. To investigate its effects on vascular inflammatory mechanisms, we elucidated vascular cytokine expression during early lesion development in A-II-infused atherosclerosis-prone LDLR −/− mice. Male LDLR −/− mice were placed on a "Western" high-fat diet for 4 weeks, followed by sham or A-II infusion for 7 weeks. Equal blood pressures and elevations in serum lipids were seen in both groups. Mice were sacrificed when significant AII-induced plaque development was first detectable, aortae were explanted and culture media assayed for secreted cytokines. Nine cytokines were significantly induced with interleukin-6 (IL-6) being the most highly secreted. Local IL-6 production was confirmed by in situ mRNA hybridization and immunostaining, where the most abundant IL-6 was found in the aortic adventitia, with lesser production by the medial and intimal layers. Immunofluorescence colocalization showed IL-6 expression by fibroblasts and activated macrophages. Activation of downstream IL-6 signaling mediated by the Jak-STAT3 pathway was demonstrated by inducible phospho-Tyr 705 -STAT3 formation in the adventitia and endothelium (of IL-6 +/+ mice only). These findings define cytokine profiles in the A-II infusion model and demonstrate that IL-6, produced by activated macrophages and fibroblasts in the adventitia, induces the Jak-STAT3 pathway during early A-II-induced atherosclerosis.

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Angiotensin II–accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice

Cited by 248 publications

References 59 publications

Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE ^−/− Mice With Unilateral Renal Artery Stenosis

Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE ^−/− Mice With Unilateral Renal Artery Stenosis

Osteopontin: Role in immune regulation and stress responses

Angiotensin II induces IL-6 expression and the Jak-STAT3 pathway in aortic adventitia of LDL receptor-deficient mice

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Angiotensin II–accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice

Cited by 248 publications

References 59 publications

Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE −/− Mice With Unilateral Renal Artery Stenosis

Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE −/− Mice With Unilateral Renal Artery Stenosis

Osteopontin: Role in immune regulation and stress responses

Angiotensin II induces IL-6 expression and the Jak-STAT3 pathway in aortic adventitia of LDL receptor-deficient mice

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Product

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Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE ^−/− Mice With Unilateral Renal Artery Stenosis

Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE ^−/− Mice With Unilateral Renal Artery Stenosis