Basement membrane remodeling in skeletal muscles of patients with limb ischemia involves regulation of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases.
OBJECTIVE
Because the pericapillary basement membrane in skeletal muscles of patients with chronic critical limb ischemia (CLI) is thickened, we determined the expression patterns of genes involved in collagen metabolism, using samples from 9 CLI patients, 4 patients with acute limb ischemia and 4 healthy controls.


METHODS
Gene array analysis, quantitative RT-PCR and semiquantitative grading of immunohistochemical reactivity were performed to determine mRNA/cDNA and protein concentrations.


RESULTS
In CLI patients compared to controls, cDNA levels of matrix metalloproteinase (MMP)-9 and MMP-19 were higher, collagen type IV chains A1 and A2, tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2 were similar and MMP-2 were lower. On the protein level, MMP-2, MMP-9, MMP-19 and TIMP-1 were more abundantly expressed. In skeletal muscles from patients with acute limb ischemia, cDNA and protein levels of MMP-9, MMP-19, collagen type IV chains, TIMP-1 and TIMP-2 were high. MMP-2 was elevated at the protein but decreased on the cDNA level.


CONCLUSIONS
Expression of basement membrane components in skeletal muscles of CLI and acute limb ischemia patients is altered, possibly contributing to the pathogenesis of peripheral arterial disease.
Baum
Oliver
O
Institute of Anatomy, University of Bern, Bern, Switzerland. oliver.baum@ana.unibe.ch
Ganster
Murielle
M
Baumgartner
Iris
I
Nieselt
Kay
K
Djonov
Valentin
V
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001485:Basement Membrane / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002908:Chronic Disease; D015331:Cohort Studies; D024141:Collagen Type IV / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007511:Ischemia / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases / Q000378:metabolism; D008833:Microcirculation / Q000378:metabolism; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism*
D024141:Collagen Type IV; D018076:DNA, Complementary; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases; C108362:matrix metalloproteinase 19; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9