The C-terminal domain of thrombospondin-1 induces vascular smooth muscle cell chemotaxis

Nesselroth, Susan M.; Willis, Alliric I.; Fuse, Shoichi; Olson, Eric T.; Lawler, Jack; Sumpio, Bauer E.; Gahtan, Vivian

doi:10.1067/mva.2001.112318

Cited by 30 publications

(23 citation statements)

References 32 publications

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“…Thrombospondin-1 (TSP-1) is a member of a protein family that mediates cell-matrix and cell-cell interactions. Experimental data have shown that TSP-1 stimulates the aggregation and stability of platelet aggregates (188), induces the expression of cell adhesion molecules (189) in endothelial cells, and stimulates chemotaxis in vascular SMCs (147,191). In TSP-1 knockout mice, more extensive postinfarction remodeling has been observed compared with wild-type mice (72).…”

Section: Adipokines With a Tight Link To Cardiovascular Diseasementioning

confidence: 96%

“…In endothelial cells, IL-4 TSP-1 -EC: 1expression of cell adhesion molecules (189) No data available -VSMC: stimulation of chemotaxis (147,191) -1Aggregation and stability of platelet aggregates (188) ACS, acute coronary syndrome; bFGF, basic fibroblast growth factor; CAD, coronary artery disease; CRP, C-reactive protein; EC, vascular endothelial cells; eNOS, endothelial nitric oxide (NO) synthase; IGT, impaired glucose tolerance; IMT, intima-media thickness; iNOS, inducible NO synthase; MMP, matrix metalloproteinase; oxLDL, oxidized low-density lipoprotein; ROS, reactive oxygen species; T2DM, type 2 diabetes mellitus; VSMC, vascular smooth muscle cells.…”

Section: Adipokines With a Tight Link To Cardiovascular Diseasementioning

confidence: 99%

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Inflammation and metabolic dysfunction: links to cardiovascular diseases

Taube

Schlich

Sell

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

203

133

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Abdominal obesity is a major risk factor for cardiovascular disease, and recent studies highlight a key role of adipose tissue dysfunction, inflammation, and aberrant adipokine release in this process. An increased demand for lipid storage results in both hyperplasia and hypertrophy, finally leading to chronic inflammation, hypoxia, and a phenotypic change of the cellular components of adipose tissue, collectively leading to a substantially altered secretory output of adipose tissue. In this review we have assessed the adipo-vascular axis, and an overview of adipokines associated with cardiovascular disease is provided. This resulted in a first list of more than 30 adipokines. A deeper analysis only considered adipokines that have been reported to impact on inflammation and NF-κB activation in the vasculature. Out of these, the most prominent link to cardiovascular disease was found for leptin, TNF-α, adipocyte fatty acid-binding protein, interleukins, and several novel adipokines such as lipocalin-2 and pigment epithelium-derived factor. Future work will need to address the potential role of these molecules as biomarkers and/or drug targets.

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Section: Adipokines With a Tight Link To Cardiovascular Diseasementioning

confidence: 96%

Section: Adipokines With a Tight Link To Cardiovascular Diseasementioning

confidence: 99%

Inflammation and metabolic dysfunction: links to cardiovascular diseases

Taube

Schlich

Sell

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

203

133

View full text Add to dashboard Cite

show abstract

“…TSP-1 is released by platelets, macrophages, monocytes, fibroblasts, vascular smooth muscle cells, and endothelial cells (42,43). TSP-1 has been shown to stimulate and inhibit EC and SMC growth (43,44) and to stimulate and inhibit angiogenesis (45). These contradictory functions have been explained by the use of different experimental approaches and the ability of TSP-1 to interact with various matrix proteins and cell-surface receptors (46).…”

Section: Discussionmentioning

confidence: 99%

Cyclic Stretch Affects Pulmonary Endothelial Cell Control of Pulmonary Smooth Muscle Cell Growth

Ochoa¹,

Baker²,

Hasak³

et al. 2008

Am J Respir Cell Mol Biol

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Endothelial cells are subjected to mechanical forces in the form of cyclic stretch resulting from blood pulsatility. Pulmonary artery endothelial cells (PAECs) produce factors that stimulate and inhibit pulmonary artery smooth muscle cell (PASMC) growth. We hypothesized that PAECs exposed to cyclic stretch secrete proteins that inhibit PASMC growth. Media from PAECs exposed to cyclic stretch significantly inhibited PASMC growth in a time-dependent manner. Lyophilized material isolated from stretched PAEC-conditioned media significantly inhibited PASMC growth in a dose-dependent manner. This inhibition was reversed by trypsin inactivation, which is consistent with the relevant factor being a protein(s). To identify proteins that inhibited cell growth in conditioned media from stretched PAECs, we used proteomic techniques and found that thrombospondin (TSP)-1, a natural antiangiogenic factor, was up-regulated by stretch. In vitro, exogenous TSP-1 inhibited PASMC growth. TSP-1-blocking antibodies reversed conditioned media-induced inhibition of PASMC growth. Cyclic stretched PAECs secrete protein(s) that inhibit PASMC proliferation. TSP-1 may be, at least in part, responsible for this inhibition. The complete identification and understanding of the secreted proteome of stretched PAECs may lead to new insights into the pathophysiology of pulmonary vascular remodeling.

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“…Inhibits adhesion of G361 melanoma cells (Prater et al and Roberts et al [13,42]). Inhibits TSP-induced chemotaxis of VSMC (Yabkowitz et al and Nesselroth et al [43,44]). Inhibits monocyte haptotaxis (Mansfield and Suchard [45]).…”

Section: E1e2mentioning

confidence: 99%

Function‐blocking antithrombospondin‐1 monoclonal antibodies

Annis

Murphy-Ullrich

Mosher

2006

Journal of Thrombosis and Haemostasis

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Summary. Background: Thrombospondin‐1 (TSP‐1) has been implicated in many different processes based in part on inhibitory activities of anti‐TSP‐1 monoclonal antibodies (mAbs). Objective: To map epitopes of 13 anti‐TSP‐1 mAbs to individual modules or groups of modules spanning TSP‐1 and the closely related TSP‐2 homolog. Results: The mapping has led to assignment or reassignment of the epitopes of four mAbs, refinement of the epitopes of six mAbs, and confirmation of the epitopes of the remaining three mAbs. ESTs10, P12, and MA‐II map to the N‐terminal domain; 5G11, TSP127.6, and ESTs12 to the third properdin module; C6.7, HB8432, and P10 to epidermal growth factor (EGF)‐like modules 1 and/or 2; and A6.1, mAb133, MA‐I, and D4.6 to the calcium‐binding wire module. A6.1, which recognizes a region of the wire that is identical in mouse and human TSP‐1, reacts with TSP‐1 from both species, and also reacts weakly with human TSP‐2. Two other mouse antihuman TSP‐1 mAbs, A4.1 and D4.6, also react with mouse TSP‐1. Conclusions: Consideration of previous literature and mapping of epitopes of inhibitory mAbs suggest that biological activities are present throughout TSP‐1, including the EGF‐like modules that have not been implicated in the past. Because the epitopes for 10 of the antibodies likely are within 18 nm of one another in calcium‐replete TSP‐1, some of the inhibitory effects may result from steric hindrance. Such seems to be the case for mAb133, which binds the calcium‐binding wire but is still able to interfere with the activation of latent TGF‐β by the properdin modules.

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The C-terminal domain of thrombospondin-1 induces vascular smooth muscle cell chemotaxis

Cited by 30 publications

References 32 publications

Inflammation and metabolic dysfunction: links to cardiovascular diseases

Inflammation and metabolic dysfunction: links to cardiovascular diseases

Cyclic Stretch Affects Pulmonary Endothelial Cell Control of Pulmonary Smooth Muscle Cell Growth

Function‐blocking antithrombospondin‐1 monoclonal antibodies

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