Ranga Robinson

St. Michael's Hospital, Toronto, Ontario, Canada

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Publications (5)48.47 Total impact

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    ABSTRACT: This study compared the extracellular matrix (ECM) and cellular responses after stenting to balloon angioplasty (BA) and to determine the late effects of matrix metalloproteinase (MMP) inhibition on arterial repair after stenting. Although stenting is the predominant form of coronary intervention, there is limited understanding of the early and late arterial response. In a double-injury rabbit model, adjacent iliac arteries in 87 animals received BA (3.0 mm diameter) or stenting (3.0 mm NIR). Rabbits were treated for 1 week postprocedure with either GM6001 (100 mg/kg per day), an MMP inhibitor or placebo and sacrificed at 1 week or at 10 weeks' postprocedure. Arteries were analyzed for morphometry, collagen content, gelatinase activity, cell proliferation and DNA content. Stented arteries had significant increases in collagen content (2-fold) at 10 weeks compared to BA-treated arteries. At one week, overall gelatinase activity was increased >2-fold in stented arteries, with both 72 kD and 92 kD gelatinase activity. Stented arteries also had increases in both intimal DNA content (1.5-fold) and absolute cell proliferation (4-fold). Compared to placebo, GM6001 significantly inhibited intimal hyperplasia and intimal collagen content, and it increased lumen area in stented arteries without effects on proliferation rates. Stenting causes a more vigorous ECM and MMP response than BA, which involves all layers of the vessel wall. Inhibition by MMP blocks in-stent intimal hyperplasia and offers a novel approach to prevent in-stent restenosis.
    Journal of the American College of Cardiology 07/2002; 39(11):1852-8. DOI:10.1016/S0735-1097(02)01873-9 · 15.34 Impact Factor
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    ABSTRACT: The role of the extracellular matrix (ECM) in the pathobiology of restenosis has not been fully appreciated. Recent discoveries have shown the ECM to be a complex, heterogeneous structure whose components are dynamically altered in response to vascular injury. This report reviews the structure and function of vascular ECM and the importance of the matrix in modulating the vascular response to arterial injury such as balloon angioplasty and atherosclerosis.
    Progress in Cardiovascular Diseases 07/1998; 41(1):35-49. DOI:10.1016/S0033-0620(98)80021-2 · 2.44 Impact Factor
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    ABSTRACT: Our concepts of the pathophysiology of restenosis have undergone several changes in the last few years. Restenosis has traditionally been attributed to the growth of a neointimal lesion, known as intimai hyperplasia (Figure 1). Smooth muscle cell (SMC) proliferation and migration were central to this concept of restenosis. This prompted research strategies to prevent restenosis by targeting (unsuccessfully) SMC proliferation. These early concepts of restenosis have been altered by the awareness of the significance of various extracellular matrix (ECM) protein accumulation (including collagen, elastin and proteoglycans) in contributing to and modulating neointimal hyperplasia. In addition, a second process, termed “vascular remodelling”, which involves a contracture of the outer vessel circumference, is now appreciated as a second important process leading to restenosis. Recent observations have also suggested that the relative contribution of these 2 processes (intimai hyperplasia and vascular remodeling) to restenosis may be quite different, depending on the type of coronary intervention. While the mechanisms responsible for intimal hyperplasia and “vascular remodeling” remain poorly understood, the extracellular matrix appears to be an integral part of the vascular response to injury in the intima and probably in the adventitia as well. Thus, the perspective in this book chapter is on the role of matrix proteins in the restenotic process.
    12/1996: pages 339-374;
  • Journal of the American College of Cardiology 02/1996; 27(2):290-290. DOI:10.1016/S0735-1097(96)82054-7 · 15.34 Impact Factor
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    ABSTRACT: Objectives This study compared the extracellular matrix (ECM) and cellular responses after stenting to balloon angioplasty (BA) and to determine the late effects of matrix metalloproteinase (MMP) inhibition on arterial repair after stenting.Background Although stenting is the predominant form of coronary intervention, there is limited understanding of the early and late arterial response.Methods In a double-injury rabbit model, adjacent iliac arteries in 87 animals received BA (3.0 mm diameter) or stenting (3.0 mm NIR). Rabbits were treated for 1 week postprocedure with either GM6001 (100 mg/kg per day), an MMP inhibitor or placebo and sacrificed at 1 week or at 10 weeks’ postprocedure. Arteries were analyzed for morphometry, collagen content, gelatinase activity, cell proliferation and DNA content.ResultsStented arteries had significant increases in collagen content (2-fold) at 10 weeks compared to BA-treated arteries. At one week, overall gelatinase activity was increased >2-fold in stented arteries, with both 72 kD and 92 kD gelatinase activity. Stented arteries also had increases in both intimal DNA content (1.5-fold) and absolute cell proliferation (4-fold). Compared to placebo, GM6001 significantly inhibited intimal hyperplasia and intimal collagen content, and it increased lumen area in stented arteries without effects on proliferation rates.Conclusions Stenting causes a more vigorous ECM and MMP response than BA, which involves all layers of the vessel wall. Inhibition by MMP blocks in-stent intimal hyperplasia and offers a novel approach to prevent in-stent restenosis.
    Journal of the American College of Cardiology 39(11):1852-1858. · 15.34 Impact Factor

Publication Stats

119 Citations
48.47 Total Impact Points

Institutions

  • 2002
    • St. Michael's Hospital
      Toronto, Ontario, Canada
  • 1998
    • Duke University Medical Center
      • Division of Cardiology
      Durham, North Carolina, United States
  • 1996
    • University of Toronto
      • Department of Medicine
      Toronto, Ontario, Canada