Antirestenotic Effects of a Locally Delivered Caspase Inhibitor in a Balloon Injury Model

Beohar, Nirat; Flaherty, James; Davidson, Charles J.; Maynard, Robert C.; Robbins, Joel D.; Shah, Atman P.; Choi, James W.; MacDonald, Lee A.; Jorgensen, Jesse P.; Pinto, Jack V.; Chandra, Sonal; Klaus, Heather M.; Wang, Norman C.; Harris, Kathleen R.; Decker, Robert S.; Bonow, Robert O.

doi:10.1161/01.cir.0000105724.30980.cd

Cited by 39 publications

(29 citation statements)

References 44 publications

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“…17,18 Moreover, the occurrence of smooth muscle cell apoptosis has been established in interventional procedures such as balloon angioplasty and stent implantation. 19,20 Unlike those previous studies, our report has shown that cells in the rabbit model undergo apoptosis within the aneurysm cavity, whereas cells in the wall of the aneurysm do not.…”

Section: Apoptosis In Endovascular Treatmentcontrasting

confidence: 88%

Molecular Indices of Apoptosis Activation in Elastase-Induced Aneurysms After Embolization With Platinum Coils

Kadirvel

Ding

Dai

et al. 2007

Stroke

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Background and Purpose-Even though endovascular coils have been widely used for the treatment of intracranial aneurysms, the cellular and molecular responses of aneurysms to the coils after embolization remain poorly understood. The aim of the present study was to understand the mechanism of apoptosis in aneurysms embolized with platinum coils in the rabbit model of elastase-induced aneurysms. Methods-Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery in 30 rabbits.Aneurysms were allowed to mature for 8 weeks, after which 20 aneurysms were embolized with platinum coils by endovascular means. After 2 (nϭ10) and 4 (nϭ10) weeks of implantation, aneurysm samples harboring coils were harvested for apoptotic studies. The remaining 10 uncoiled aneurysms were used as controls; additional controls included the left common carotid artery, which had not undergone any surgical procedure. Control samples were harvested at 12 weeks after aneurysm creation. Results-Expression of procaspases-3, -8, and -9 was elevated in coiled aneurysms embolized with platinum coils at both time points when compared with uncoiled aneurysms and the left common carotid artery. Cleaved caspases-3, -8, and -9 were found to be expressed only at 4 weeks after embolization. Cells within the aneurysm cavity were terminal dUTP nick end-labeling-positive at 4 weeks only. These apoptotic cells were identified as smooth muscle actin-positive cells. Expression of tumor necrosis-␣ was high in coiled aneurysms when compared with controls. There was no significant difference in the expression of Fas ligand among groups. Decreased expression of antiapoptotic proteins Bcl-2 and phospho-Bad, as well as increased expression of proapoptotic proteins Bax and Bid, was observed in coiled aneurysms at both time points. Conclusions-Activation of apoptosis in aneurysms after embolization with platinum coils is induced by both tumor necrosis factor-␣-mediated extrinsic and Bcl-2-mediated intrinsic pathways.

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Section: Apoptosis In Endovascular Treatmentcontrasting

confidence: 88%

Molecular Indices of Apoptosis Activation in Elastase-Induced Aneurysms After Embolization With Platinum Coils

Kadirvel

Ding

Dai

et al. 2007

Stroke

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“…More importantly, the hVSMC response to bilirubin at the tested high physiological concentration does not cause apoptosis as shown by annexin V staining. This absence of apoptosis is significant given recent reports that apoptosis of VSMCs can trigger the development of neointima formation (20).…”

Section: Discussionmentioning

confidence: 83%

Essential Roles of Raf/Extracellular Signal-regulated Kinase/Mitogen-activated Protein Kinase Pathway, YY1, and Ca2+ Influx in Growth Arrest of Human Vascular Smooth Muscle Cells by Bilirubin

Stoeckius

Erat

Fujikawa

et al. 2012

Journal of Biological Chemistry

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Background: Bilirubin circulates throughout the human cardiovascular system. Its interaction with the vascular wall is not well known. Results: Bilirubin alters Raf/ERK/MAPK pathway, cellular transcription factor YY1 location, and calcium-dependent YY1 proteolysis in human vascular cells. Conclusion: At high physiological levels bilirubin, inhibits cell growth, inhibits proliferation, and does not cause apoptosis. Significance: The observations provide opportunities for prevention and treatment of cardiovascular diseases.

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“…The lack of apoptosis in our model is likely important given recent reports that apoptosis of VSMCs can trigger the development of neointima formation. 29 Bilirubin peaks analyzed by HPLC in whole cell lysates increased significantly (AU 3.6Ϯ0.4 times versus control) measured 8 hours after biliverdin treatment. Considering the fact that the bilirubin and biliverdin effects on VSMC proliferation were independent of HO-1 expression, as tested in VSMCs from HO-1 knockout cells (data not shown), we assume the bilirubin we measured was converted from biliverdin rather than being generated by HO-1 induction.…”

Section: Discussionmentioning

confidence: 93%

Bilirubin

et al. 2005

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Background-Bilirubin, a natural product of heme catabolism by heme oxygenases, was considered a toxic waste product until 1987, when its antioxidant potential was recognized. On the basis of observations that oxidative stress is a potent trigger in vascular proliferative responses, that heme oxygenase-1 is antiatherogenic, and that several studies now show that individuals with high-normal or supranormal levels of plasma bilirubin have a lesser incidence of atherosclerosisrelated diseases, we hypothesized that bilirubin would have salutary effects on preventing intimal hyperplasia after balloon injury. Methods and Results-We found less balloon injury-induced neointima formation in hyperbilirubinemic Gunn rats and in wild-type rats treated with biliverdin, the precursor of bilirubin, than in controls. In vitro, bilirubin and biliverdin inhibited serum-driven smooth muscle cell cycle progression at the G 1 phase via inhibition of the mitogen-activated protein kinase signal transduction pathways and inhibition of phosphorylation of the retinoblastoma tumor suppressor protein. Conclusions-Bilirubin and biliverdin might be potential therapeutics in vascular proliferative disorders. (Circulation.

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Antirestenotic Effects of a Locally Delivered Caspase Inhibitor in a Balloon Injury Model

Cited by 39 publications

References 44 publications

Molecular Indices of Apoptosis Activation in Elastase-Induced Aneurysms After Embolization With Platinum Coils

Molecular Indices of Apoptosis Activation in Elastase-Induced Aneurysms After Embolization With Platinum Coils

Essential Roles of Raf/Extracellular Signal-regulated Kinase/Mitogen-activated Protein Kinase Pathway, YY1, and Ca2+ Influx in Growth Arrest of Human Vascular Smooth Muscle Cells by Bilirubin

Bilirubin

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