Decreased vascular matrix metalloproteinase abundance in diabetic patients with symptomatic macroangiopathy

J. Sheppard Mondy, Mark P. Anstadt, Dion L. Franga, Vera Portik-Dobos, Jimmie Hutchinson, Adviye Ergul

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The incidence of diabetic amputations is 2- to 3-fold higher in African-American patients compared to Caucasians. Vascular remodeling characterized by extracellular matrix (ECM) deposition occurs in diabetes and contributes to vascular complications. The matrix metalloproteinases (MMP) play important roles in the regulation of collagen turnover and vascular remodeling. However, the temporal expression profile of MMPs in diabetic vascular tissue during the disease process remained unknown. The objective of this study was to compare the vascular MMP system in African-American diabetic patients without symptoms to patients undergoing lower limb amputation due to severe vascular complications. Internal mammary artery (IMA, N=8) and anterior/posterior tibial artery (AT/PT, N=8) specimens were obtained from patients undergoing coronary artery bypass grafting and lower limb amputation, respectively. ECM inducer protein (EMMPRIN) and MMP activator membrane-type MMP (MT1-MMP), as well as MMP-1, -2, and -9, were quantified by immunoblotting and densitometry (pixels). MMP-1 and -9 levels were decreased from 398 ± 61 and 175 ± 54 pixels, respectively, in IMA tissue to 287 ± 31 and 51 ± 36 pixels in the AT/PT tissue (P<.05). Both EMMPRIN and MT1-MMP expression was increased by 3-fold in AT/PT preparations (P<.05). These results provided evidence that the molecular components required for the induction and activation of the MMP system exist in arterial vasculature and, MMP expression is downregulated in diabetic patients with severe complications despite elevated MMP inducer and activator proteins. Decreased MMP activity may contribute to pathological remodeling leading to increased incidence of amputations in African-American patients.

Original languageEnglish (US)
JournalEthnicity and Disease
Volume12
Issue number4
StatePublished - Sep 1 2002
Externally publishedYes

Fingerprint

Matrix Metalloproteinases
Blood Vessels
Amputation
African Americans
Tibial Arteries
Matrix Metalloproteinase 14
Matrix Metalloproteinase 1
Lower Extremity
Membrane-Associated Matrix Metalloproteinases
Mammary Arteries
Densitometry
Extracellular Matrix Proteins
Matrix Metalloproteinase 2
Incidence
Matrix Metalloproteinase 9
Immunoblotting
Coronary Artery Bypass
Extracellular Matrix
Collagen
Down-Regulation

Keywords

  • African-American
  • Amputation
  • Diabetes
  • Matrix metalloproteinase

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Medicine(all)

Cite this

Mondy, J. S., Anstadt, M. P., Franga, D. L., Portik-Dobos, V., Hutchinson, J., & Ergul, A. (2002). Decreased vascular matrix metalloproteinase abundance in diabetic patients with symptomatic macroangiopathy. Ethnicity and Disease, 12(4).

Decreased vascular matrix metalloproteinase abundance in diabetic patients with symptomatic macroangiopathy. / Mondy, J. Sheppard; Anstadt, Mark P.; Franga, Dion L.; Portik-Dobos, Vera; Hutchinson, Jimmie; Ergul, Adviye.

In: Ethnicity and Disease, Vol. 12, No. 4, 01.09.2002.

Research output: Contribution to journalArticle

Mondy, JS, Anstadt, MP, Franga, DL, Portik-Dobos, V, Hutchinson, J & Ergul, A 2002, 'Decreased vascular matrix metalloproteinase abundance in diabetic patients with symptomatic macroangiopathy', Ethnicity and Disease, vol. 12, no. 4.
Mondy JS, Anstadt MP, Franga DL, Portik-Dobos V, Hutchinson J, Ergul A. Decreased vascular matrix metalloproteinase abundance in diabetic patients with symptomatic macroangiopathy. Ethnicity and Disease. 2002 Sep 1;12(4).
Mondy, J. Sheppard ; Anstadt, Mark P. ; Franga, Dion L. ; Portik-Dobos, Vera ; Hutchinson, Jimmie ; Ergul, Adviye. / Decreased vascular matrix metalloproteinase abundance in diabetic patients with symptomatic macroangiopathy. In: Ethnicity and Disease. 2002 ; Vol. 12, No. 4.
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