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The expression of LDL receptor in vessels with blood–brain barrier impairment in a stroke-prone hypertensive model

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Abstract

We previously reported that the blood–brain barrier (BBB) function was deteriorated in vessels located in the hippocampus in stroke-prone spontaneously hypertensive rats (SHRSP). In order to assess whether substances with oxidative stress such as amyloid-β (Aβ) can be scavenged in the BBB-damaged vessels, we examined the gene expression of representative efflux and influx transporters of Aβ, such as low-density lipoprotein receptor (LDLR), LDL-related protein 1 (LRP1), and the receptor for advanced glycation end product (RAGE) in the hippocampus of SHRSP with the BBB impairment and Wistar Kyoto rats (WKY) without the impairment. Real-time quantitative reverse transcriptase-polymerase chain reaction analysis revealed that LDLR gene expression was increased in the samples of SHRSP compared with those of WKY, while there was no significant difference in LRP1 or RAGE gene expression between SHRSP and WKY. Western blot analysis revealed that the protein expression of LDLR was increased in the samples of SHRSP compared with those of WKY. Immunoelectron microscopic examination revealed that the LDLR expression was seen in the luminal and abluminal cytoplasmic membranes and vesicular structures of the endothelial cells and the cytoplasm of perivascular cells, especially in vessels with immunoreactivity of albumin showing increased vascular permeability. These findings suggest that the expression of LDLR was increased in the hippocampus of SHRSP compared with that of WKY and was seen in the luminal and abluminal cytoplasmic membranes and vesicular structures of endothelial cells, suggesting a role of LDLR in the vessels with BBB impairment.

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Acknowledgments

This research was supported by a budget from the Ministry of Education, Culture, Sports, Science and Technology of Japan and a fund (M.O.) for exploratory research for young scientists from the Faculty of Medicine, Kagawa University, 2009. We would like to thank Ms M. Kawauchi for technical assistance and Ms A. Kimura for editorial assistance.

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Authors and Affiliations

  1. Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan

    Masaki Ueno, Bin Wu, Masayuki Onodera & Haruhiko Sakamoto

  2. Life Sciences Research Center, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Toshitaka Nakagawa & Yukiko Nagai

  3. Department of Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Cheng-long Huang

  4. Maternal and Perinatal Center, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Takashi Kusaka

  5. Department of Perinatology and Gynecology, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Kenji Kanenishi

  6. Department of Gynecology and Obstetrics, Second Affiliated Hospital of China Medical University, San Hao Road 36, Shenyang, 110003, China

    Bin Wu

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  1. Masaki Ueno
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  2. Bin Wu
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  3. Toshitaka Nakagawa
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  9. Haruhiko Sakamoto
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Correspondence to Masaki Ueno.

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Ueno, M., Wu, B., Nakagawa, T. et al. The expression of LDL receptor in vessels with blood–brain barrier impairment in a stroke-prone hypertensive model. Histochem Cell Biol 133, 669–676 (2010). https://doi.org/10.1007/s00418-010-0705-y

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