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Vitamin D receptor activation modulates the biology of vascular smooth muscle cells and has been reported to protect from neointimal hyperplasia following endothelial injury. However, the molecular mechanisms are poorly understood. We have now explored the impact of the selective vitamin D receptor activator, paricalcitol, on neointimal hyperplasia, following guidewire-induced endothelial cell injury in rats, and we have assessed the impact of paricalcitol or vehicle on the expression of key cell stress factors. Guidewire-induced endothelial cell injury caused neointimal hyperplasia and luminal stenosis and upregulated the expression of the growth factor growth\/differentiation factor-15 (GDF-15), the cytokine receptor CD74, NF\u03baB-inducing kinase (NIK, an upstream regulator of the proinflammatory transcription factor NF\u03baB) and the chemokine monocyte chemoattractant protein-1 (MCP-1\/CCL2). Immunohistochemistry confirmed the increased expression of the cellular proteins CD74 and NIK. Paricalcitol (administered in doses of 750 ng\/kg of body weight, every other day) had a non-significant impact on neointimal hyperplasia and luminal stenosis. However, it significantly decreased GDF-15, CD74, NIK and MCP-1\/CCL2 mRNA expression, which in paricalcitol-injured arteries remained within the levels found in control vehicle sham arteries. In conclusion, paricalcitol had a dramatic effect, suppressing the stress response to guidewire-induced endothelial cell injury, despite a limited impact on neointimal hyperplasia and luminal stenosis. This observation identifies novel molecular targets of paricalcitol in the vascular system, whose differential expression cannot be justified as a consequence of improved tissue injury.<\/jats:p>","DOI":"10.3390\/ijms25094814","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T08:02:22Z","timestamp":1714723342000},"page":"4814","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Paricalcitol Has a Potent Anti-Inflammatory Effect in Rat Endothelial Denudation-Induced Intimal Hyperplasia"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1190-7068","authenticated-orcid":false,"given":"Ciro","family":"Baeza","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery, IIS-Fundacion Jimenez Diaz UAM, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arancha","family":"Pintor-Chocano","sequence":"additional","affiliation":[{"name":"RICORS2040, 28049 Madrid, Spain"},{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Carrasco","sequence":"additional","affiliation":[{"name":"RICORS2040, 28049 Madrid, Spain"},{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Sanz","sequence":"additional","affiliation":[{"name":"RICORS2040, 28049 Madrid, Spain"},{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9805-9523","authenticated-orcid":false,"given":"Alberto","family":"Ortiz","sequence":"additional","affiliation":[{"name":"RICORS2040, 28049 Madrid, Spain"},{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28040 Madrid, Spain"},{"name":"Departamento de Medicina, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7110-6409","authenticated-orcid":false,"given":"Maria Dolores","family":"Sanchez-Ni\u00f1o","sequence":"additional","affiliation":[{"name":"RICORS2040, 28049 Madrid, Spain"},{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28040 Madrid, Spain"},{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1056\/NEJM199405193302008","article-title":"The Emerging Concept of Vascular Remodeling","volume":"330","author":"Epstein","year":"1994","journal-title":"N. 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