Absence of heme oxygenase-1 exacerbates atherosclerotic lesion formation and vascular remodeling - PubMed (original) (raw)

. 2003 Sep;17(12):1759-61.

doi: 10.1096/fj.03-0187fje. Epub 2003 Jul 3.

Affiliations

• PMID: 12958201
• DOI: 10.1096/fj.03-0187fje

Absence of heme oxygenase-1 exacerbates atherosclerotic lesion formation and vascular remodeling

Shaw-Fang Yet et al. FASEB J. 2003 Sep.

Abstract

To examine the role of heme oxygenase (HO)-1 in the pathophysiology of vascular diseases, we generated mice deficient in both HO-1 and apolipoprotein E (HO-1-/-apoE-/-). Despite similar total plasma cholesterol levels in response to hypercholesterolemia, HO-1-/-apoE-/- mice, in comparison with HO-1+/+apoE-/- mice, had an accelerated and more advanced atherosclerotic lesion formation. In addition to greater lipid accumulation, these advanced lesions from HO-1-/-apoE-/- mice contained macrophages and smooth muscle alpha-actin-positive cells. We further tested the role of HO-1 on neointimal formation in a mouse model of vein graft stenosis. Autologous vein grafts in HO-1-/- mice showed robust neointima consisting of alpha-actin-positive vascular smooth muscle cells (VSMC) 10 days after surgery in comparison to the smaller neointima formed in autologous vein grafts in HO-1+/+ mice. However, at 14 days after surgery, the neointima from composite vessels of HO-1-/- mice was composed mainly of acellular material, indicative of substantial VSMC death. VSMC isolated from HO-1-/- mice were susceptible to oxidant stress, leading to cell death. Our data demonstrate that HO-1 plays an essential protective role in the pathophysiology of atherosclerosis and vein graft stenosis.

PubMed Disclaimer

Similar articles

• Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of atherosclerosis in apolipoprotein E-deficient mice.
  Juan SH, Lee TS, Tseng KW, Liou JY, Shyue SK, Wu KK, Chau LY. Juan SH, et al. Circulation. 2001 Sep 25;104(13):1519-25. doi: 10.1161/hc3801.095663. Circulation. 2001. PMID: 11571246
• Rapid development of vein graft atheroma in ApoE-deficient mice.
  Dietrich H, Hu Y, Zou Y, Huemer U, Metzler B, Li C, Mayr M, Xu Q. Dietrich H, et al. Am J Pathol. 2000 Aug;157(2):659-69. doi: 10.1016/S0002-9440(10)64576-2. Am J Pathol. 2000. PMID: 10934168 Free PMC article.
• Accelerated atherosclerosis and calcification in vein grafts: a study in APOE*3 Leiden transgenic mice.
  Lardenoye JH, de Vries MR, Löwik CW, Xu Q, Dhore CR, Cleutjens JP, van Hinsbergh VW, van Bockel JH, Quax PH. Lardenoye JH, et al. Circ Res. 2002 Oct 4;91(7):577-84. doi: 10.1161/01.res.0000036901.58329.d7. Circ Res. 2002. PMID: 12364385
• Role of heme oxygenase-1 in cardiovascular function.
  Perrella MA, Yet SF. Perrella MA, et al. Curr Pharm Des. 2003;9(30):2479-87. doi: 10.2174/1381612033453776. Curr Pharm Des. 2003. PMID: 14529547 Review.
• Heme oxygenase as an intrinsic defense system in vascular wall: implication against atherogenesis.
  Ishikawa K, Maruyama Y. Ishikawa K, et al. J Atheroscler Thromb. 2001;8(3):63-70. doi: 10.5551/jat1994.8.63. J Atheroscler Thromb. 2001. PMID: 11866032 Review.

Cited by

• Exacerbation of oxidative stress-induced cell death and differentiation in induced pluripotent stem cells lacking heme oxygenase-1.
  Lin CY, Peng CY, Huang TT, Wu ML, Lai YL, Peng DH, Chen PF, Chen HF, Yen BL, Wu KK, Yet SF. Lin CY, et al. Stem Cells Dev. 2012 Jul 1;21(10):1675-87. doi: 10.1089/scd.2011.0304. Epub 2011 Dec 16. Stem Cells Dev. 2012. PMID: 22034921 Free PMC article.
• High-mobility group box 1 contributes to lethality of endotoxemia in heme oxygenase-1-deficient mice.
  Takamiya R, Hung CC, Hall SR, Fukunaga K, Nagaishi T, Maeno T, Owen C, Macias AA, Fredenburgh LE, Ishizaka A, Blumberg RS, Baron RM, Perrella MA. Takamiya R, et al. Am J Respir Cell Mol Biol. 2009 Aug;41(2):129-35. doi: 10.1165/rcmb.2008-0331OC. Epub 2008 Dec 18. Am J Respir Cell Mol Biol. 2009. PMID: 19097991 Free PMC article.
• Oxidative risk for atherothrombotic cardiovascular disease.
  Leopold JA, Loscalzo J. Leopold JA, et al. Free Radic Biol Med. 2009 Dec 15;47(12):1673-706. doi: 10.1016/j.freeradbiomed.2009.09.009. Epub 2009 Sep 12. Free Radic Biol Med. 2009. PMID: 19751821 Free PMC article. Review.
• Activation of mitogen-activated protein kinases by lysophosphatidylcholine-induced mitochondrial reactive oxygen species generation in endothelial cells.
  Watanabe N, Zmijewski JW, Takabe W, Umezu-Goto M, Le Goffe C, Sekine A, Landar A, Watanabe A, Aoki J, Arai H, Kodama T, Murphy MP, Kalyanaraman R, Darley-Usmar VM, Noguchi N. Watanabe N, et al. Am J Pathol. 2006 May;168(5):1737-48. doi: 10.2353/ajpath.2006.050648. Am J Pathol. 2006. PMID: 16651638 Free PMC article.
• The Role of NRF2 in Obesity-Associated Cardiovascular Risk Factors.
  Gutiérrez-Cuevas J, Galicia-Moreno M, Monroy-Ramírez HC, Sandoval-Rodriguez A, García-Bañuelos J, Santos A, Armendariz-Borunda J. Gutiérrez-Cuevas J, et al. Antioxidants (Basel). 2022 Jan 26;11(2):235. doi: 10.3390/antiox11020235. Antioxidants (Basel). 2022. PMID: 35204118 Free PMC article. Review.

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Wiley

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)

• Miscellaneous

  • NCI CPTAC Assay Portal