Pentoxifylline ameliorates chronic stress/high-fat diet-induced vascular wall disease: the role of circulating endothelial progenitor cells
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Depression and cardiovascular disease (CVD) are two faces of one coin. A pro-inflammatory state was previously suggested in the pathology of both diseases. We investigated the effect of chronic administration (2 weeks) of imipramine (20 mg/kg/day) and pentoxifylline (50 mg/kg/day) on behavioral, aortic histological abnormalities, and level of circulating endothelial progenitor cells (CEPCs) in peripheral blood of male Wistar rats exposed to chronic mild stress (CMS) and high-fat diet. Exposure to CMS and high-fat diet induced a depressive-like behavior alongside aortic immunohistochemical changes associated with an increase in aortic TNF-α level. Markers of CEPCs, VEGFR-2 and CD133, were significantly disturbed in aortic sections, as compared to control animals and those exposed to CMS while fed high-fat diet, although flowcytometric analysis did not show any significant changes in the level of CEPCs in peripheral blood. Chronic pentoxifylline treatment was more effective in ameliorating the histological changes and endothelial damage compared to imipramine. Pro-inflammatory cytokines-induced disturbances in CEPCs could constitute a plausible link between depression and atherosclerotic cardiovascular disease. Current antidepressants reduce symptoms of depression without tackling the underlying link between it and cardiovascular disease. Targeting pro-inflammatory cytokines might open a new therapeutic approach to alleviate depression and reduce the risk of mortality from cardiovascular disease.
KeywordsPentoxifylline Imipramine Endothelial progenitor cells Cardiovascular diseases High-fat diet
Conceived and designed the experiments: AA, KF, MM, and SA. Performed the experiments: JL, SA, and AA. Analyzed the data: JL and MH. Contributed reagents/materials/analysis tools: JL, SA, MM, KF, and AA. Wrote the paper: MH and JL.
Compliance with ethical standards
All procedures were conducted in accordance with the approval of the Research Ethics Committee at the Faculty of Medicine, Ain Shams University, (FMASU-REC).
Conflict of interest
The authors declare that they have no conflict of interest.
The present study was approved by the Research Ethics Committee of the Faculty of Medicine, Ain Shams University (FMASU-REC). FMASU-REC operates under Federal Wide Assurance.
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