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Microvascular Lesions by Estrogen-Induced ID3: Its Implications in Cerebral and Cardiorenal Vascular Disease

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Abstract

Severe symptoms of cerebral and cardiorenal vascular diseases can be triggered when cerebral, coronary, or glomerular arterioles grow inappropriately as a result of abnormal cell proliferation. The risk factor(s) and molecular mechanisms responsible for microvascular lesion formation are largely unknown. Although controversial, both animal and epidemiological studies have shown that estrogen increases the risk of stroke which may be due to microvascular lesions. Since microvascular diseases are characterized by excessive vessel growth, it is plausible that estrogen-induced neovascularization contributes to the growth of microvascular lesions. We present evidence for how ID3 overexpression in endothelial cells contributes to the development of an estrogen-induced neovascular phenotype with an additional focus on Pyk2 kinase. Our data showed that ID3 overexpression increased neovascularization, cell migration, and spheroid growth of human cerebral microvascular endothelial cells, hCMEC/D3. ID3-overexpressing cells showed significant estrogen-induced G2/M phase transition. Estrogen treatment increased both ID3 phosphorylation; total protein that was inhibited by tamoxifen, and Pyk2-mediated estrogen-induced ID3 mRNA expression. These findings suggest that Pyk2 signals ID3 expression and ID3 is necessary for estrogen-induced neovascularization in hCMEC/D3 cells. A better understanding of how microvascular lesions depend on ID3 may open new avenues for prevention and treatment of neurological diseases.

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Acknowledgments

This research is supported by grants from NIH SC3 Award (1SC3GM084827-01A1).

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  1. Department of Environmental and Occupational Health, Florida International University, 11200 SW 8th Street, AHC-2 Bldg. Rm 593, Miami, FL, USA

    Jayanta K. Das & Quentin Felty

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  1. Jayanta K. Das
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  2. Quentin Felty
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Correspondence to Quentin Felty.

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Das, J.K., Felty, Q. Microvascular Lesions by Estrogen-Induced ID3: Its Implications in Cerebral and Cardiorenal Vascular Disease. J Mol Neurosci 55, 618–631 (2015). https://doi.org/10.1007/s12031-014-0401-9

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  • DOI: https://doi.org/10.1007/s12031-014-0401-9

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