title: Cross-talk between macrophages, smooth muscle cells, and endothelial cells in response to cigarette smoke: the effects on MMP2 and 9.
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.
authors: Section of Vascular Surgery, Department of Surgery, Jobst Vascular Research Laboratories, University of Michigan Medical School, Ann Arbor, MI, USA.
authors: Abhijit
authors: A
authors: Ghosh
authors: Section of Vascular Surgery, Department of Surgery, Jobst Vascular Research Laboratories, University of Michigan Medical School, Ann Arbor, MI, USA.
authors: L V T Angela
authors: LV
authors: Pechota
authors: Division of Vascular and Endovascular Surgery, University of Virginia, PO Box 800679, Charlottesville, VA, USA.
authors: Gilbert R
authors: GR
authors: Upchurch
authors: Section of Vascular Surgery, Department of Surgery, Jobst Vascular Research Laboratories, University of Michigan Medical School, Ann Arbor, MI, USA. jonaelia@med.umich.edu.
authors: Jonathan L
authors: JL
authors: Eliason
mesh_terms: D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000201:enzymology; D002450:Cell Communication / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology; D053614:Janus Kinase 2 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation; D000067996:RAW 264.7 Cells; D051381:Rats; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*
chemical_list: D017077:Culture Media, Conditioned; D050796:STAT3 Transcription Factor; D012906:Smoke; C494087:Stat3 protein, mouse; C494088:Stat3 protein, rat; C507926:Jak2 protein, mouse; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; C572337:Mmp9 protein, rat
keywords: Abdominal aortic aneurysm; Cellular interactions; Cigarette smoke; MMP2; MMP9