Wound healing: A paradigm for lumen narrowing after arterial reconstruction

Geary, Randolph L.; Nikkari, Seppo T.; Wagner, William D.; Williams, J. Koudy; Adams, Michael R.; Dean, Richard H.

doi:10.1016/s0741-5214(98)70296-4

Cited by 113 publications

(113 citation statements)

References 39 publications

Supporting

Mentioning

104

Contrasting

Unclassified

Order By: Relevance

“…Although data are not available on the fate of versican during the regression process in this model, it is of interest to note that immunohistochemical analysis of versican (using 2B1 against the G3 globular domain) in human arteries after balloon angioplasty showed an accumulation of versican during the first 3 months and a decrease thereafter (Imanaka-Yoshida et al 2001, Matsuura et al 1996. A similar pattern was also observed in nonhuman primate arteries after balloon angioplasty (Geary et al 1998). Like angioplasty, stent placement also initially stimulates intimal hyperplasia in animal models and human arteries.…”

Section: Versican Metabolism In Intimal Regressionsupporting

confidence: 67%

Versican Degradation and Vascular Disease

Kenagy

Plaas

Wight³

2006

Trends in Cardiovascular Medicine

View full text Add to dashboard Cite

Versican is an abundant proteoglycan in the blood vessel wall that is increased after vascular injury and accumulates in advanced atherosclerotic plaques. Versican is a large molecule with domains that mediate binding to cytokines, enzymes, lipoproteins, other extracellular matrix molecules, and signaling receptors. There is evidence that versican exists in the normal, as well as the diseased, vessel wall as discrete fragments, which represent these functional domains. We review the literature on versican degradation in vascular tissue and the function of versican domains, all of which suggest that proteolytic modification of versican may have physiologic as well as pathologic implications for the vascular system.

show abstract

Section: Versican Metabolism In Intimal Regressionsupporting

confidence: 67%

Versican Degradation and Vascular Disease

Kenagy

Plaas

Wight³

2006

Trends in Cardiovascular Medicine

View full text Add to dashboard Cite

show abstract

“…31 However, numerous vascular diseases are characterized by the accumulation of smooth muscle cells in the intimal layer of blood vessels where they are surrounded by newly synthesized extracellular Wnt3a alters smooth muscle cell phenotype JM Carthy et al matrix. 3,4,32 These cells are generally thought of as dedifferentiated and synthetic, in that they display a loss of contractile differentiation, but an increased capacity to synthesize matrix proteins. 31 Although traditionally it has been thought that smooth muscle cells existed in either a synthetic or contractile state, it is now being recognized that there is considerable heterogeneity in smooth muscle cell populations and in some instances, contractile differentiation markers may be expressed simultaneously with matrix synthesis.…”

Section: Discussionmentioning

confidence: 99%

WNT3A induces a contractile and secretory phenotype in cultured vascular smooth muscle cells that is associated with increased gap junction communication

Carthy

Luo

McManus

2012

Laboratory Investigation

View full text Add to dashboard Cite

Evidence suggests a role for Wnt signaling in vascular wound repair and remodeling events. Despite this, very little is known about the effect of Wnt ligands on the structure and function of vascular cells. In this study, we treated vascular smooth muscle cells with 250 ng/ml of recombinant Wnt3a for 72 h and observed changes in the cell phenotype. Our data suggest Wnt3a completely alters the phenotype of vascular smooth muscle cells. The Wnt3a-treated cells appeared larger and had increased formation of stress fibers. These cells also had increased expression of the smooth muscle contractile proteins, calponin and smooth muscle a-actin, and contracted a collagen lattice faster than control cells. The Wnt3a-treated smooth muscle cells displayed increased extracellular matrix synthesis, as measured by collagen I and III mRNA expression, along with increased expression of MMP2 and MMP9, but decreased TIMP2 levels. The Wnt3a-induced change in cell phenotype was associated with increased expression of the gap junction protein connexin 43. Consistent with this, Wnt3a-treated smooth muscle cells displayed enhanced intercellular communication, as measured by the scrape-loading dye transfer technique. The canonical Wnt antagonist, dickkopf-related protein 1, completely reversed the contractile protein and connexin 43 expression seen in the Wnt3a-treated cells, suggesting these changes were dependent on canonical Wnt signaling. Collectively, this data suggest Wnt3a promotes a contractile and secretory phenotype in vascular smooth muscle cells that is associated with increased gap junction communication. Numerous studies have demonstrated that after arterial injury, vessel walls follow a response-to-injury pattern of wound healing leading to stenosis secondary to the neointimal accumulation of smooth muscle cells and extracellular matrix. 1-4 A number of soluble mediators released at the site of vascular injury act as molecular cues that guide smooth muscle cell responses during repair. 5,6 Growing evidence suggest a role for the Wnt family of secreted glycoproteins and their associated signaling pathways in regulating many of the processes involved in vascular wound repair and remodeling events. [7][8][9][10][11][12][13][14] However, the precise mechanisms and outcomes of Wnt signaling in such settings remain unclear. Moreover, the effect of specific Wnt family members on vascular cell phenotype remain undefined.The Wnt signaling pathway is best recognized for its role in the development of multi-cellular organisms, 15,16 and is critically involved in normal heart formation. 17 The Wnt family is comprised of 19 secreted glycoproteins that bind the Frizzled receptor and its co-receptor, lipoprotein receptorrelated proteins 5/6, to initiate an intracellular signaling cascade that controls the turnover of b-catenin. 18 In the absence of Wnt ligand, b-catenin is targeted for ubiquitinmediated degradation by the 26S proteasome. However, upon ligand stimulation, canonical Wnt signaling triggers a series of phosphorylation even...

show abstract

“…Geary et al 48 demonstrated that the spatial temporal pattern of events after angioplasty, including deposition of extracellular matrix, is quite analogous to healing wounds and culminates in luminal narrowing. In addition to the physical wounds caused by angioplasty, plaque fractures and plaque ruptures can also be viewed as "wounds," which may eventually result in luminal narrowing as a result of normal prolonged wound healing.…”

Section: Discussionmentioning

confidence: 99%

Homocysteine Binds to Human Plasma Fibronectin and Inhibits Its Interaction With Fibrin

Majors

Sengupta

Willard

et al. 2002

ATVB

View full text Add to dashboard Cite

Objective-More than 70% of circulating homocysteine is disulfide-bonded to protein, but little is known about the specific proteins that bind homocysteine and their function as a consequence of homocysteine binding. Methods and Results-When human plasma was incubated with [35 S]L-homocysteine, most of the homocysteine bound to albumin. However, additional homocysteine-binding proteins were detected, and 1 of them comigrated with fibronectin. Treatment with 2-mercaptoethanol removed the bound homocysteine, demonstrating the involvement of disulfide bonding. In contrast, [35 S]L-cysteine did not bind to fibronectin. Purified fibronectin bound Ϸ5 homocysteine molecules per fibronectin dimer. SDS-PAGE of a limited trypsin digestion of homocysteinylated fibronectin showed that several tryptic fragments contained [35 S]homocysteine. Sequence analysis demonstrated that the fragments containing bound homocysteine had localized mainly to the C-terminal region, within and adjacent to the fibrin-binding domain. Homocysteinylation of fibronectin significantly inhibited its capacity to bind fibrin by 62% (PϽ0.005). In contrast, neither the binding of fibronectin to gelatin nor its capacity to serve as an attachment factor for aortic smooth muscle cells was affected. Key Words: homocysteine Ⅲ fibronectin Ⅲ fibrin Ⅲ atherosclerosis Ⅲ thrombosis H omocysteine is a sulfhydryl-containing amino acid formed during the metabolism of methionine. In healthy well-nourished individuals, homocysteine metabolism is efficient and regulated, and the concentration of plasma total homocysteine is usually Յ12 mol/L. 1 Inborn errors of homocysteine metabolism, drugs that interfere with homocysteine metabolism, deficiencies of folic acid, vitamin B 6 or vitamin B 12 , and certain disease states, such as chronic renal failure, increase plasma total homocysteine levels. 2 The homocystinurias are a heterogeneous group of autosomal recessive diseases caused by inborn errors of homocysteine metabolism. [3][4][5] Patients with untreated homocystinuria have severe hyperhomocysteinemia (50 to 500 mol/L) and lifethreatening premature cardiovascular disease. Thrombosis, with or without embolism, is the major cause of death. Postmortem studies show multiple thrombotic occlusions and widespread premature atherosclerosis with intimal thickening. However, even mild hyperhomocysteinemia (15 to 25 mol/L), regardless of the underlying cause, is a strong independent risk factor for occlusive vascular disease, as shown by numerous case-control and prospective studies involving thousands of subjects. 1,2,6 The mechanisms of homocysteine-induced atherosclerosis and thrombosis have not been fully elucidated. Conclusions-TheseIn normal individuals, Ͼ70% of circulating homocysteine is disulfide-bonded to plasma proteins. 7,8 The primary carrier of disulfide-bound homocysteine is albumin, 9 -12 but other proteins with accessible cysteine residues are also potential carriers. The binding of homocysteine to cysteine residues may disrupt normal protein structure and impair...

show abstract

Wound healing: A paradigm for lumen narrowing after arterial reconstruction

Cited by 113 publications

References 39 publications

Versican Degradation and Vascular Disease

Versican Degradation and Vascular Disease

WNT3A induces a contractile and secretory phenotype in cultured vascular smooth muscle cells that is associated with increased gap junction communication

Homocysteine Binds to Human Plasma Fibronectin and Inhibits Its Interaction With Fibrin

Contact Info

Product

Resources

About