A nonintrinsic regional basis for increased infrarenal aortic MMP-9 expression and activity.
OBJECTIVE
This investigation was undertaken to determine whether intrinsic or regional factors at different anatomic sites of the aorta affect expression and activity of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs).


METHODS
Aortas from Sprague-Dawley rats (n = 22) were divided into arch, descending thoracic, and infrarenal abdominal segments. Specimens were stimulated with interleukin-1beta (IL-1beta) (2 ng/mL) for 72 hours. In separate experiments, syngeneic aortic segments were transplanted from the thoracic or abdominal aortas of donor rats into the infrarenal aortic position of recipient rats (n = 12 each). At 4 weeks, aortas from rats who had received transplants were harvested, sectioned into arch, thoracic, and transplanted thoracic or transplanted abdominal segments, and stimulated with IL-1beta. Reverse transcriptase polymerase chain reaction, zymography, and reverse zymography were performed to assess MMP-9, MMP-2, and TIMP-1 in all aortic segments. Differences were assessed with analysis of variance (ANOVA) and post-hoc Tukey test.


RESULTS
In control rats, abdominal segments had significantly higher MMP-9 expression compared with arch and thoracic segments (P <.002). Total MMP-9 activity was also higher in abdominal segments (P <.02). In rats who received transplants, transplanted thoracic (P <.004) and transplanted abdominal (P <.05) segments demonstrated upregulation of MMP-9 expression, compared with control arch and thoracic segments. Zymography documented increased total MMP-9 activity in transplanted thoracic (P <.03) and transplanted abdominal (P <.04) segments versus arch and thoracic segments. No significant difference in MMP-9 expression was found between control abdominal, transplanted thoracic, or transplanted abdominal segments. No significant differences in MMP-2 or TIMP-1 expression or activity were demonstrated in either control or transplanted segments.


CONCLUSIONS
These data demonstrate that variations in aortic MMP-9 expression and activity result from regional factors affecting the aorta rather than intrinsic aortic wall differences. Increases in abdominal aortic MMP-9 may contribute to the predilection for aneurysm to develop in the infrarenal aorta.
Ailawadi
Gorav
G
Jobst Vascular Research Laboratories, Section of Vascular Surgery, Ann Arbor, Mich, USA.
Knipp
Brian S
BS
Lu
Guanyi
G
Roelofs
Karen J
KJ
Ford
John W
JW
Hannawa
Kevin K
KK
Bishop
Keith
K
Thanaporn
Porama
P
Henke
Peter K
PK
Stanley
James C
JC
Upchurch
Gilbert R
GR
D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001012:Aorta, Abdominal / Q000201:enzymology* / Q000473:pathology / Q000637:transplantation; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism / Q000601:surgery; D001794:Blood Pressure / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004492:Edetic Acid / Q000494:pharmacology; D005780:Gelatin / Q000187:drug effects / Q000378:metabolism; D018093:Gelatinases / Q000187:drug effects / Q000378:metabolism; D006339:Heart Rate / Q000502:physiology; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D008955:Models, Cardiovascular; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000187:drug effects / Q000378:metabolism
D000199:Actins; D002614:Chelating Agents; D007976:Leupeptins; D011480:Protease Inhibitors; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D010664:Phenylmethylsulfonyl Fluoride; D005780:Gelatin; D004492:Edetic Acid; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C032854:leupeptin