Morphologic characteristics of varicose veins: Possible role of metalloproteinases

Kenneth J. Woodside, Mingdao Hu, Ann Burke, Maki Murakami, Lori Pounds, Lois A. Killewich, John A. Daller, Glenn C. Hunter

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Background: Although varicose veins are a common cause of morbidity, etiologic factors predisposing to dilatation, elongation, and tortuosity of the saphenous vein and its tributaries are poorly understood. We compared histologic features of normal and varicose saphenous veins and investigated the role of enzyme or inhibitor imbalance in development of varicosities. Methods: Eight normal and 10 varicose (C2,3EP,SASP R,O) vein segments were used for this analysis. Matrix metalloproteinase (MMP) expression and activity were analyzed with Western blotting and zymography. Venous architecture and protein localization were determined with histology and immunohistochemistry. Results: Western blot analysis demonstrated the presence of MMP- 1, MMP-2, MMP-9, and MMP-12, as well as small quantities of tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 in protein isolates from normal and varicose veins. Both vein types demonstrated MMP-2, MMP-9, and MMP-12 activity by gelatin zymography, although varicose vein expressed less MMP-9 activity than normal vein did. Compared with normal veins, changes in varicose veins were not uniformly distributed along the circumference; areas of intimal thickening were often interspersed with focal areas of dilatation. Fragmentation of elastic lamellae and loss of circular and longitudinal muscle fibers were evident in the varicosities. Focal aggregates of macrophages were detected within the media and adventitia of both normal and varicose veins. MMP-1 and MMP-9 were expressed in both types of vein segments; however, their immunohistochemical localization was distinctly different. In normal vein, endothelial cells, occasional smooth muscle cells (SMC), and adventitial microvessels expressed MMP-1, whereas its expression was localized to fibroblasts, SMC, and endothelial cells throughout involved portions of varicose veins. MMP-9 was localized to endothelial cells, medial SMC, and adventitial microvessels in both normal and varicose veins, although varicose veins demonstrated increased medial smooth muscle cell staining. MMP-12 was found in SMC and fibroblasts in both normal and varicose veins. Neither TIMP-1 nor TIMP-2 were detected with immunohistochemistry in any specimens examined. Conclusions: There are distinct differences in the structural architecture and localization of MMP expression in normal and varicose veins. Although the changes observed are not sufficiently definitive to enable a causal relationship, they do suggest a possible mechanism for the alterations in matrix composition observed between normal and varicose veins.

Original languageEnglish (US)
Pages (from-to)162-169
Number of pages8
JournalJournal of Vascular Surgery
Volume38
Issue number1
DOIs
StatePublished - Jul 2003
Externally publishedYes

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Varicose Veins
Metalloproteases
Matrix Metalloproteinase 9
Veins
Matrix Metalloproteinase 12
Smooth Muscle Myocytes
Adventitia
Matrix Metalloproteinase 1
Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinase-1
Endothelial Cells
Matrix Metalloproteinase 2
Saphenous Vein
Microvessels
Matrix Metalloproteinases
Dilatation
Fibroblasts
Western Blotting
Immunohistochemistry
Tunica Intima

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Woodside, K. J., Hu, M., Burke, A., Murakami, M., Pounds, L., Killewich, L. A., ... Hunter, G. C. (2003). Morphologic characteristics of varicose veins: Possible role of metalloproteinases. Journal of Vascular Surgery, 38(1), 162-169. https://doi.org/10.1016/S0741-5214(03)00134-4

Morphologic characteristics of varicose veins : Possible role of metalloproteinases. / Woodside, Kenneth J.; Hu, Mingdao; Burke, Ann; Murakami, Maki; Pounds, Lori; Killewich, Lois A.; Daller, John A.; Hunter, Glenn C.

In: Journal of Vascular Surgery, Vol. 38, No. 1, 07.2003, p. 162-169.

Research output: Contribution to journalArticle

Woodside, KJ, Hu, M, Burke, A, Murakami, M, Pounds, L, Killewich, LA, Daller, JA & Hunter, GC 2003, 'Morphologic characteristics of varicose veins: Possible role of metalloproteinases', Journal of Vascular Surgery, vol. 38, no. 1, pp. 162-169. https://doi.org/10.1016/S0741-5214(03)00134-4
Woodside, Kenneth J. ; Hu, Mingdao ; Burke, Ann ; Murakami, Maki ; Pounds, Lori ; Killewich, Lois A. ; Daller, John A. ; Hunter, Glenn C. / Morphologic characteristics of varicose veins : Possible role of metalloproteinases. In: Journal of Vascular Surgery. 2003 ; Vol. 38, No. 1. pp. 162-169.
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AU - Woodside, Kenneth J.

AU - Hu, Mingdao

AU - Burke, Ann

AU - Murakami, Maki

AU - Pounds, Lori

AU - Killewich, Lois A.

AU - Daller, John A.

AU - Hunter, Glenn C.

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N2 - Background: Although varicose veins are a common cause of morbidity, etiologic factors predisposing to dilatation, elongation, and tortuosity of the saphenous vein and its tributaries are poorly understood. We compared histologic features of normal and varicose saphenous veins and investigated the role of enzyme or inhibitor imbalance in development of varicosities. Methods: Eight normal and 10 varicose (C2,3EP,SASP R,O) vein segments were used for this analysis. Matrix metalloproteinase (MMP) expression and activity were analyzed with Western blotting and zymography. Venous architecture and protein localization were determined with histology and immunohistochemistry. Results: Western blot analysis demonstrated the presence of MMP- 1, MMP-2, MMP-9, and MMP-12, as well as small quantities of tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 in protein isolates from normal and varicose veins. Both vein types demonstrated MMP-2, MMP-9, and MMP-12 activity by gelatin zymography, although varicose vein expressed less MMP-9 activity than normal vein did. Compared with normal veins, changes in varicose veins were not uniformly distributed along the circumference; areas of intimal thickening were often interspersed with focal areas of dilatation. Fragmentation of elastic lamellae and loss of circular and longitudinal muscle fibers were evident in the varicosities. Focal aggregates of macrophages were detected within the media and adventitia of both normal and varicose veins. MMP-1 and MMP-9 were expressed in both types of vein segments; however, their immunohistochemical localization was distinctly different. In normal vein, endothelial cells, occasional smooth muscle cells (SMC), and adventitial microvessels expressed MMP-1, whereas its expression was localized to fibroblasts, SMC, and endothelial cells throughout involved portions of varicose veins. MMP-9 was localized to endothelial cells, medial SMC, and adventitial microvessels in both normal and varicose veins, although varicose veins demonstrated increased medial smooth muscle cell staining. MMP-12 was found in SMC and fibroblasts in both normal and varicose veins. Neither TIMP-1 nor TIMP-2 were detected with immunohistochemistry in any specimens examined. Conclusions: There are distinct differences in the structural architecture and localization of MMP expression in normal and varicose veins. Although the changes observed are not sufficiently definitive to enable a causal relationship, they do suggest a possible mechanism for the alterations in matrix composition observed between normal and varicose veins.

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