Involvement of the tyrosinase gene in the deposition of cardiac lipofuscin in mice. Association with aortic fatty streak development.

Qiao, Jian-Hua; Welch, Carrie L.; Xie, Peizhen; Fishbein, Michael C.; Lusis, Aldons J.

doi:10.1172/jci116844

Cited by 19 publications

(12 citation statements)

References 41 publications

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“…In contrast, PGPC induced both monocyte and neutrophil binding by stimulating the expression of E-selectin and VCAM-1. VCAM-1 has been shown to be strongly expressed in the luminal endothelium of rabbits (32) and mice (33) in the areas of monocyte entry. In human atherosclerotic lesions both CS-1 (5) and VCAM-1 (34) are expressed, though VCAM-1 is expressed mainly on adventitial microvessels.…”

Section: Discussionmentioning

confidence: 99%

Structurally similar oxidized phospholipids differentially regulate endothelial binding of monocytes and neutrophils

Leitinger

Tyner

Oslund

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

226

229

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We previously have demonstrated that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC), a component of minimally modified low density lipoprotein (MM-LDL), activates endothelial cells to bind monocytes. 1-Palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine (PGPC), which are present in OxPAPC, MM-LDL, and atherosclerotic lesions, were shown to have a major role in the activation of endothelial cells. We now demonstrate that these two highly similar molecules have dramatically different effects on leukocyte endothelial interactions. POVPC is a potent regulator of monocyte-specific endothelial interactions. Treatment of endothelial cells with POVPC increased monocyte binding by inducing the surface expression of the connecting segment 1 domain of fibronectin; no increase in neutrophil binding was observed. In addition, POVPC strongly inhibited lipopolysaccharide-mediated induction of neutrophil binding and expression of E-selectin protein and mRNA. This inhibition was mediated by a protein kinase A-dependent pathway, resulting in down-regulation of NF-B-dependent transcription. In contrast, PGPC induced both monocyte and neutrophil binding and expression of E-selectin and vascular cell adhesion molecule 1. We present evidence to suggest that the two phospholipids act by different novel receptors present in Xenopus laevis oocytes and that POVPC, but not PGPC, stimulates a cAMP-mediated pathway. At concentrations equal to that present in MM-LDL, the effect of POVPC dominates and inhibits PGPC-induced neutrophil binding and Eselectin expression in endothelial cells. In summary, our data provide evidence that both POVPC and PGPC are important regulators of leukocyte-endothelial interactions and that POVPC may play a dominant role in a number of chronic inflammatory processes where oxidized phospholipids are known to be present.

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Section: Discussionmentioning

confidence: 99%

Structurally similar oxidized phospholipids differentially regulate endothelial binding of monocytes and neutrophils

Leitinger

Tyner

Oslund

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

226

229

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“…P-and E-selectin deficiency leads to a reduction in both early and late stages of atherosclerotic lesion development, indicating that under conditions that are optimal for lesion development, the net effect of the macrophage recruitment is proatherogenic. The lipofuscin data suggest that decreased macrophage infiltration into lesions in the absence of both selectins may lead to a reduction in oxidized LDL production; the lipofuscin pigment consists of terminally oxidized polyunsaturated lipid and protein complexes, and there are common pathways contributing to oxidized LDL, lipofuscin, and fatty streak development (14). Decreased oxidized LDL in lesions may result in reduction in lesion progression because oxidized LDL is known to stimulate expression of adhesion molecules on endothelium leading to additional cellular infiltration and is the main source of lipid in foam cells (1).…”

Section: Discussionmentioning

confidence: 99%

“…To assess lipofuscin accumulation on the surface of the aortic valve leaflets, unstained even-numbered slides were examined by light microscopy for the presence of yellow-brown lipofuscin pigment deposits (14). The presence of lipofuscin in any 1 of 20 sections (five slides) defined the mouse as lipofuscin-positive.…”

Section: Methodsmentioning

confidence: 99%

The combined role of P- and E-selectins in atherosclerosis.

et al. 1998

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P-and E-selectins are adhesion molecules mediating the first step in leukocyte extravasation. Because their function in leukocyte adhesion is overlapping, we hypothesized that there might be a combined effect of these selectins on the development of atherosclerotic lesions. We bred P-and E-selectin-double-deficient mice onto the low-density lipoprotein receptor (LDLR)-deficient background (LDLR Ϫ / Ϫ P/E Ϫ / Ϫ ) and compared lesion development in these mice to that in mice wild type for both selectins (LDLR Ϫ / Ϫ P/E ϩ / ϩ ). After 8 wk on atherogenic diet, the LDLR Ϫ / Ϫ P/E Ϫ / Ϫ mice developed fatty streaks in the aortic sinus that were five times smaller than those in LDLR Ϫ / Ϫ P/E ϩ / ϩ mice. The density of macrophages in the fatty streaks was comparable between LDLR Ϫ / Ϫ P/E ϩ / ϩ and LDLR Ϫ / Ϫ P/E Ϫ / Ϫ mice. After 22 wk on the diet, the lesions spread throughout the aorta but this process was delayed in LDLR Ϫ / Ϫ P/E Ϫ / Ϫ mice. At 37 wk on diet, the lesions progressed to the fibrous plaque stage in both genotypes. However, the lesions in the aortic sinus in LDLR Ϫ / Ϫ P/E Ϫ / Ϫ mice were 40% smaller and less calcified than those of LDLR Ϫ / Ϫ P/E ϩ / ϩ mice.

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“…After killing the upper portion of the heart and proximal aorta were embedded in OCT compound and frozen on dry ice. Serial 10-/tm-thick cryosections of aorta, beginning at the aortic root, were collected for a distance of -400 ttm (35,36). These sections were stained with oil red 0 and hematoxylin.…”

Section: Methodsmentioning

confidence: 99%

Genetic evidence for a common pathway mediating oxidative stress, inflammatory gene induction, and aortic fatty streak formation in mice.

Liao¹,

Andalibi²,

Qiao³

et al. 1994

J. Clin. Invest.

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223

132

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Involvement of the tyrosinase gene in the deposition of cardiac lipofuscin in mice. Association with aortic fatty streak development.

Cited by 19 publications

References 41 publications

Structurally similar oxidized phospholipids differentially regulate endothelial binding of monocytes and neutrophils

Structurally similar oxidized phospholipids differentially regulate endothelial binding of monocytes and neutrophils

The combined role of P- and E-selectins in atherosclerosis.

Genetic evidence for a common pathway mediating oxidative stress, inflammatory gene induction, and aortic fatty streak formation in mice.

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