DOI: 10.1161/01.res.88.5.506. Heme Oxygenase-1 Inhibits Atherosclerotic Lesion Formation in LDL-Receptor Knockout Mice

Heme Oxygenase-1 Inhibits Atherosclerotic Lesion Formation in LDL-Receptor Knockout Mice

10.1161/01.res.88.5.506

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Circulation Research (276)

Abstract

Abstract —Heme oxygenase-1 (HO-1) is induced by a variety of conditions associated with oxidative stress. We demonstrated that mildly oxidized LDL markedly induces HO-1 in human aortic endothelial and smooth muscle cell cocultures and that its induction results in the attenuation of monocyte chemotaxis resulting from treatment with mildly oxidized LDL in vitro. To elucidate the role of HO-1 in the development of atherosclerotic lesions in vivo, we modulated HO-1 expression in LDL-receptor knockout mice fed high-fat diets. During 6-week high-fat diet trials, intraperitoneal injections of hemin (H group) or hemin and desferrioxamine (HD group) to induce HO-1, Sn-protoporphyrin IX to inhibit HO-1 (Sn group), and saline as control (C group) were performed. Both the H and HD groups showed significantly less mean atherosclerotic lesions in the proximal aorta compared with the C group, whereas the Sn group showed larger lesion compared with the C group. Modulation of HO expression and HO activities were confirmed by Northern blot analysis and HO activity assay. Immunohistochemical studies revealed significant HO-1 expression in atherosclerotic lesions, where oxidized phospholipids also localized. Major cell types expressing HO-1 were macrophages and foam cells in the lesions. HO modulations affected plasma lipid hydroperoxide (LPO) levels and nitrite/nitrate levels. These results suggest that HO-1, induced under hyperlipidemia, functioned as an intrinsic protective factor against atherosclerotic lesion formation, possibly by inhibiting lipid peroxidation and influencing the nitric oxide pathway.

Bibliography

Ishikawa, K., Sugawara, D., Wang, X., Suzuki, K., Itabe, H., Maruyama, Y., & Lusis, A. J. (2001). Heme Oxygenase-1 Inhibits Atherosclerotic Lesion Formation in LDL-Receptor Knockout Mice. Circulation Research, 88(5), 506â512.

Authors 7

Kazunobu Ishikawa (first)
Daisuke Sugawara (additional)
Xu-ping Wang (additional)
Kazunori Suzuki (additional)
Hiroyuki Itabe (additional)
Yukio Maruyama (additional)
Aldons J. Lusis (additional)

References 54 Referenced 216

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Dates

Type	When
Created	13 years, 2 months ago (June 11, 2012, 8:52 p.m.)
Deposited	1 year, 3 months ago (May 12, 2024, 4:31 p.m.)
Indexed	1 month, 3 weeks ago (July 8, 2025, 4:27 p.m.)
Issued	24 years, 5 months ago (March 16, 2001)
Published	24 years, 5 months ago (March 16, 2001)
Published Print	24 years, 5 months ago (March 16, 2001)

Funders 0

None

BibTeX

@article{Ishikawa_2001, title={Heme Oxygenase-1 Inhibits Atherosclerotic Lesion Formation in LDL-Receptor Knockout Mice}, volume={88}, ISSN={1524-4571}, url={http://dx.doi.org/10.1161/01.res.88.5.506}, DOI={10.1161/01.res.88.5.506}, number={5}, journal={Circulation Research}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Ishikawa, Kazunobu and Sugawara, Daisuke and Wang, Xu-ping and Suzuki, Kazunori and Itabe, Hiroyuki and Maruyama, Yukio and Lusis, Aldons J.}, year={2001}, month=mar, pages={506–512} }

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  "URL": "http://dx.doi.org/10.1161/01.RES.88.5.506",
  "relation": {},
  "ISSN": [
    "0009-7330",
    "1524-4571"
  ],
  "subject": [],
  "container-title-short": "Circulation Research",
  "published": {
    "date-parts": [
      [
        2001,
        3,
        16
      ]
    ]
  },
  "assertion": [
    {
      "value": "2001-03-16",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}