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Cross-talk between macrophages, smooth muscle cells, and endothelial cells in response to cigarette smoke: the effects on MMP2 and 9

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Abstract

We hypothesized that matrix metalloproteinase secretion in response to cigarette smoke is modulated by cross-talk between resident cells within the aorta, namely, aortic smooth muscles, endothelial cells, and infiltrating macrophages, and this may be crucial for in vivo formation/progression of abdominal aortic aneurysm (AAA). Cigarette smoke extract (CSE) was applied to rat aortic smooth muscle (RASMC), endothelial (RAEC) or RAW cells, and conditioned media (CSE-CM) collected. Fresh cells were treated with CSE-CM for 24 h and then maintained in serum-free medium (SFM) for 72 h to analyze MMP2 and MMP9 in media by zymography and the ratio (pS/pJ) of phospho-Stat3 (pStat3) and phospho-Jak2 (pJak2) inside the cells by Western blot. We observed that CSE-CM from RAW and RAEC increased MMP9 by 200 and 17 %, respectively, in RASMC and also increased pS/pJ ratio (305 and 228 %, respectively) in RASMC. RAW cell-derived CSE-CM induced RAEC to produce moderate amounts of MMP2 (17 %), MMP9 (30 %), and a 137 % increase in pS/pJ. RAW cells receiving unstimulated CM from RASMC and RAEC produced significant amounts of MMP9 (128 and 155 %, respectively) and increased pS/pJ (45 and 1283 %, respectively). CSE-CM from RASMC and RAEC induced significant production of MMP9 from RAW cells (237 and 162 %, respectively) and increase in pS/pJ ratios (1348 and 1494 %, respectively). This is the first in vitro study demonstrating cigarette smoke extract-mediated differential interactions between resident cells in the aorta leads to altered modulation of signaling molecules that may be vital for AAA formation under in vivo conditions.

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Acknowledgments

The Aortic Research Center of the Jobst Vascular Research Laboratory at the University of Michigan extends a heartfelt thank you to A. J. Bartoletto for his ongoing support of aortic aneurysm research. This work was supported by the Frankel Cardiovascular Center of the University of Michigan to JLE.

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Authors and Affiliations

  1. Section of Vascular Surgery, Department of Surgery, Jobst Vascular Research Laboratories, University of Michigan Medical School, Ann Arbor, MI, USA

    Abhijit Ghosh, L. V. T. Angela Pechota & Jonathan L. Eliason

  2. Division of Vascular and Endovascular Surgery, University of Virginia, PO Box 800679, Charlottesville, VA, USA

    Gilbert R. Upchurch Jr.

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  1. Abhijit Ghosh
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  2. L. V. T. Angela Pechota
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  3. Gilbert R. Upchurch Jr.
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Correspondence to Jonathan L. Eliason.

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Ghosh, A., Pechota, L.V.T.A., Upchurch, G.R. et al. Cross-talk between macrophages, smooth muscle cells, and endothelial cells in response to cigarette smoke: the effects on MMP2 and 9. Mol Cell Biochem 410, 75–84 (2015). https://doi.org/10.1007/s11010-015-2539-3

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