Endothelial transcytosis of myeloperoxidase confers specificity to vascular ECM proteins as targets of tyrosine nitration

Baldus, Stephan; Eiserich, Jason P.; Mani, Ali R.; Castro, Laura; Figueroa, Mario; Chumley, Phillip; Ma, Wenxin; Tousson, Albert; White, C. Roger; Bullard, Daniel C.; Brennan, Marie–Luise; Lusis, Aldons J.; Moore, Kevin; Freeman, Bruce Α.

doi:10.1172/jci12617

Cited by 174 publications

(188 citation statements)

References 75 publications

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“…Endothelial cells do represent the physiological target for adhesion, arrest, and transmigration of cells and proteins. HOCl-modified epitopes are abundantly present in situ, and endothelial cells bind and internalize MPO (68) and HOCl-modified lipoproteins (43), leading to impairment of endothelial function (19). Both MPO and HOClmodified epitopes are abundantly present in various tissues under inflammatory conditions (7, 23, 69 -72).…”

Section: Discussionmentioning

confidence: 99%

Class B Scavenger Receptors CD36 and SR-BI Are Receptors for Hypochlorite-modified Low Density Lipoprotein

Marsche

Zimmermann

Horiuchi

et al. 2003

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Class B Scavenger Receptors CD36 and SR-BI Are Receptors for Hypochlorite-modified Low Density Lipoprotein

Marsche

Zimmermann

Horiuchi

et al. 2003

Journal of Biological Chemistry

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“…l7 Moreover, MPO has also been shown to nitrate tyrosine residues during their transcytosis across endothelial cells. 7 The specific location of 3-nitrotyrosine and iNOS may implicate that, during the transcytosis of iNOS, and possibly MPO, intracellular proteins are nitrated at their tyrosine residue. This may in turn deplete the energy source of the BEC, leading to cell death.…”

Section: Discussionmentioning

confidence: 99%

Myeloperoxidase-positive inflammatory cells participate in bile duct damage in primary biliary cirrhosis through nitric oxide-mediated reactions

Eiserich

Ansari

et al. 2003

Hepatology

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Previous studies have suggested that increased nitric oxide (NO)-mediated products are found in the livers of subjects with primary biliary cirrhosis (PBC), but the mechanisms involved remain enigmatic. We took advantage of immunohistochemistry and several unique monoclonal antibodies to study inflammatory cells responsible for the generation of NO, the enzymes responsible for NO production, the expression of 3-nitrOtyrOSine, and the presence of CD68' and/or myeloperoxidase (MPO) + cells. We examined a total of 1 13 liver specimens, including 64 with PBC, 19 with primary sclerosing cholangitis (PSC), 6 with non-A, non-B hepatitis, 6 with alcoholic liver disease, 4 with cryptogenic cirrhosis, 4 with biliary atresia, and 10 normal subjects. Twentytwo percent of PBC had elevated expression of hitrotyrosine in their bile duct epithelial cells (BECs) (P = ,0316). Furthermore, the BEG in PBC also demonstrated apoptotic changes.MPO-positive inflammatory cells were also noted adjacent to the basement membrane. In contrast, the liver of normal subjects showed few apoptotic changes in the bile ducts, with no evidence of MPO staining in the portal area.

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“…In human atherosclerotic lesions, most cell-associated myeloperoxidase is found in and around macrophages (16). However, the enzyme has also been detected in endothelial cells (42), raising the possibility that reactive intermediates produced by peroxidases might generate the epitopes on macrophages and endothelial cells that are recognized by antibodies to 3-nitrotyrosine.…”

mentioning

confidence: 99%

Human Atherosclerotic Intima and Blood of Patients with Established Coronary Artery Disease Contain High Density Lipoprotein Damaged by Reactive Nitrogen Species

Pennathur

Bergt

Shao

et al. 2004

Journal of Biological Chemistry

254

230

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High density lipoprotein (HDL) is the major carrier of lipid hydroperoxides in plasma, but itis not yet established whether HDL proteins are damaged by reactive nitrogen species in the circulation or artery wall. One pathway that generates such species involves myeloperoxidase (MPO), a major constituent of artery wall macrophages. Another pathway involves peroxynitrite, a potent oxidant generated in the reaction of nitric oxide with superoxide. Both MPO and peroxynitrite produce 3-nitrotyrosine in vitro. To investigate the involvement of reactive nitrogen species in atherogenesis, we quantified 3-nitrotyrosine levels in HDL in vivo. The mean level of 3-nitrotyrosine in HDL isolated from human aortic atherosclerotic intima was 6-fold higher (619 ؎ 178 mol/mol Tyr) than that in circulating HDL (104 ؎ 11 mol/mol Tyr; p < 0.01). Immunohistochemical studies demonstrated striking colocalization of MPO with epitopes reactive with an antibody to 3-nitrotyrosine. However, there was no significant correlation between the levels of 3-chlorotyrosine, a specific product of MPO, and those of 3-nitrotyrosine in lesion HDL. We also detected 3-nitrotyrosine in circulating HDL, and linear regression analysis demonstrated a strong correlation between the levels of 3-chlorotyrosine and levels of 3-nitrotyrosine. These observations suggest that MPO promotes the formation of 3-chlorotyrosine and 3-nitrotyrosine in circulating HDL but that other pathways also produce 3-nitrotyrosine in atherosclerotic tissue. Levels of HDL isolated from plasma of patients with established coronary artery disease contained twice as much 3-nitrotyrosine as HDL from plasma of healthy subjects, suggesting that nitrated HDL might be a marker for clinically significant vascular disease. The detection of 3-nitrotyrosine in HDL raises the possibility that reactive nitrogen species derived from nitric oxide might promote atherogenesis. Thus, nitrated HDL might represent a previously unsuspected link between nitrosative stress, atherosclerosis, and inflammation.

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Endothelial transcytosis of myeloperoxidase confers specificity to vascular ECM proteins as targets of tyrosine nitration

Cited by 174 publications

References 75 publications

Class B Scavenger Receptors CD36 and SR-BI Are Receptors for Hypochlorite-modified Low Density Lipoprotein

Class B Scavenger Receptors CD36 and SR-BI Are Receptors for Hypochlorite-modified Low Density Lipoprotein

Myeloperoxidase-positive inflammatory cells participate in bile duct damage in primary biliary cirrhosis through nitric oxide-mediated reactions

Human Atherosclerotic Intima and Blood of Patients with Established Coronary Artery Disease Contain High Density Lipoprotein Damaged by Reactive Nitrogen Species

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