PMID- 12844103
OWN - NLM
STAT- MEDLINE
DCOM- 20030729
LR  - 20190823
IS  - 0741-5214 (Print)
IS  - 0741-5214 (Linking)
VI  - 38
IP  - 1
DP  - 2003 Jul
TI  - Transient exposure to elastase induces mouse aortic wall smooth muscle cell 
      production of MCP-1 and RANTES during development of experimental aortic 
      aneurysm.
PG  - 138-46
AB  - PURPOSE: Abdominal aortic aneurysm (AAA) is associated with chronic transmural 
      inflammation and destruction of the elastic media. The purpose of this study was 
      to elucidate molecular mechanisms that might orchestrate leukocyte recruitment 
      into the outer aortic wall by determining whether CC chemokines contribute to 
      development of aneurysm degeneration in an elastase-induced mouse model of AAA. 
      METHODS: Adult male C57BL/6J mice underwent transient elastase perfusion of the 
      abdominal aorta to induce development of AAA. At various intervals after elastase 
      perfusion (0, 4, 7, 14 days), real-time reverse transcription polymerase chain 
      reaction and enzyme-linked immunosorbent assays were used to measure aortic wall 
      expression of the CC (beta) chemokines, monocyte chemoattractant protein-1 
      (MCP-1) and regulated on activation, normal T-cell expressed and secreted 
      (RANTES). Expression of these chemokines by cultured mouse aortic smooth muscle 
      cells (AoSMC) was similarly assessed after transient (5 minutes) exposure to 
      elastase solutions in vitro. RESULTS: Mouse aortic diameter (mean +/- SEM) 
      increased to aneurysmal proportions by 14 days after elastase perfusion (from 
      0.51 +/- 0.03 mm to 1.34 +/- 0.32 mm; 163% increase; P <.05), with macrophage 
      infiltration of the outer aortic wall beginning within 7 to 10 days. Increased 
      aortic wall messenger RNA expression for MCP-1 (28-fold) and RANTES (11-fold) was 
      observed on day 4, with maximal production of chemokine protein on day 7 (MCP-1, 
      from 7.07 +/- 0.06 ng/mL to 19.60 +/- 0.19 ng/mL; P <.001; RANTES, from 0.23 +/- 
      0.006 ng/mL to 2.03 +/- 0.057 ng/mL; P <.001). Neither MCP-1 nor RANTES was 
      detected in normal mouse aorta with immunohistochemistry, but both chemokines 
      were abundant in AAA. Within 48 hours of transient exposure to elastase, cultured 
      mouse AoSMC exhibited pronounced induction (>90-fold) of MCP-1 and RANTES, 
      despite concomitant decrease in cell numbers. CONCLUSIONS: Increased mouse aortic 
      wall expression of MCP-1 and RANTES occurs early in development of 
      elastase-induced AAA and before onset of the chronic inflammatory response. 
      Moreover, elastase directly stimulates AoSMC chemokine production in vitro. 
      Elastase-induced medial SMC production of CC chemokines may therefore provide an 
      important link between enzymatic injury, leukocyte recruitment, and aneurysmal 
      degeneration of the aortic wall.
FAU - Colonnello, Jamie S
AU  - Colonnello JS
AD  - Department of Surgery, Section of Vascular Surgery, Washington University School 
      of Medicine, St. Louis, Missouri 63110, USA.
FAU - Hance, Kirk A
AU  - Hance KA
FAU - Shames, Murray L
AU  - Shames ML
FAU - Wyble, Charles W
AU  - Wyble CW
FAU - Ziporin, Scott J
AU  - Ziporin SJ
FAU - Leidenfrost, Jeremy E
AU  - Leidenfrost JE
FAU - Ennis, Terri L
AU  - Ennis TL
FAU - Upchurch, Gilbert R Jr
AU  - Upchurch GR Jr
FAU - Thompson, Robert W
AU  - Thompson RW
LA  - eng
GR  - HL56701/HL/NHLBI NIH HHS/United States
GR  - HL64333/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Vasc Surg
JT  - Journal of vascular surgery
JID - 8407742
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Chemokines, CC)
RN  - EC 3.4.21.36 (Pancreatic Elastase)
SB  - IM
MH  - Animals
MH  - Aorta, Abdominal/*drug effects/metabolism
MH  - Aortic Aneurysm, Abdominal/metabolism/*physiopathology
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis
MH  - Chemokine CCL5/*biosynthesis
MH  - Chemokines, CC/biosynthesis
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Models, Animal
MH  - Muscle, Smooth, Vascular/*drug effects/metabolism
MH  - Pancreatic Elastase/*pharmacology
EDAT- 2003/07/05 05:00
MHDA- 2003/07/30 05:00
CRDT- 2003/07/05 05:00
PHST- 2003/07/05 05:00 [pubmed]
PHST- 2003/07/30 05:00 [medline]
PHST- 2003/07/05 05:00 [entrez]
AID - S0741521403001253 [pii]
AID - 10.1016/s0741-5214(03)00125-3 [doi]
PST - ppublish
SO  - J Vasc Surg. 2003 Jul;38(1):138-46. doi: 10.1016/s0741-5214(03)00125-3.