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LOX-1 Deletion Limits Cardiac Angiogenesis in Mice Given Angiotensin II

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Abstract

Lectin-like oxidized low-density lipoprotein (ox-LDL) receptor-1 (LOX-1) is a major receptor for ox-LDL in endothelial cells. Its activation regulates endothelial proliferation, differentiation, migration and apoptosis. Recent in vitro studies show that LOX-1 activation by ox-LDL and angiotensin II (Ang II) induces angiogenesis via activation of NADPH oxidase and subsequent increase in ROS production. In this study, we investigated the effect of LOX-1 gene deletion (LOX-1 knockout or KO mice) on angiogenesis in response to prolonged Ang II infusion in vivo. Our studies showed that Ang II (vs. saline) infusion enhanced capillary formation in subcutaneously injected Matrigel® plugs. Ang II infusion also resulted in marked angiogenesis in the hearts as determined by CD31 immunopositivity. There was an increased expression (RT-PCR and Western blotting) of CD31 and VEGF in the hearts of mice infused with Ang II, indicating pro-angiogenic miliue. More importantly, LOX-1 KO mice reveled markedly limited angiogenesis in the Matrigel® plugs as well as in the hearts despite similar infusion with Ang II (all P < 0.05 vs. wild-type mice). In addition, the hearts of LOX-1 KO mice had attenuated expression of pro-inflammatory and angiogenic signals MCP-1 and IL-1β following Ang II Infusion. Lastly, the rise in blood pressure in response to Ang II was less in the LOX-1 KO mice (P < 0.05 vs. wild-type mice). Our findings suggest that LOX-1 participates in angiogenesis in hypertension, which may be related to a state of inflammation.

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Acknowledgments

This study was supported by funds from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development, Washington, DC. Additional funds were provided by Grant (No. 81370428) from the National Natural Science Foundation of China. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Conflict of Interest

The authors declared no conflict of interest.

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Authors and Affiliations

  1. Department of Medicine, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, AR, 72212, USA

    Xianwei Wang, Magomed Khaidakov, Zufeng Ding & Jawahar L Mehta

  2. Key Laboratory of Henan Province for Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China

    Xianwei Wang & Zhikun Guo

  3. The Third Hospital of Xinxiang Medical University, Xinxiang, China

    Quanzhong He

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  1. Xianwei Wang
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  2. Magomed Khaidakov
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  3. Zhikun Guo
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  4. Zufeng Ding
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  5. Quanzhong He
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  6. Jawahar L Mehta
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Correspondence to Xianwei Wang.

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Wang, X., Khaidakov, M., Guo, Z. et al. LOX-1 Deletion Limits Cardiac Angiogenesis in Mice Given Angiotensin II. Cardiovasc Drugs Ther 28, 441–446 (2014). https://doi.org/10.1007/s10557-014-6541-x

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  • DOI: https://doi.org/10.1007/s10557-014-6541-x

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