Removal of an Inhibitor of Marker Enzyme Activity in Artery Extracts by Chelating Agents

Oswald, H; Heinemann, Frank; Nikol, Sigrid; Salmons, Brian; Günzburg, Walter H.

doi:10.2144/97221bm16

Cited by 8 publications

(2 citation statements)

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“…In the pCMVb -treated pigs the b -galactosidase activity in the myocardial tissue was evaluated with a chem iluminescence assay (Tropix, Bedford, MA). Before measuring b -galactosidase activity, tissue homogenates were pretreated with Chelex 100 to inactivate a natural inhibitor of the enzyme (Oswald et al, 1997).…”

Section: Evaluation Of Gene Expressionmentioning

confidence: 99%

Intramyocardial Gene Therapy with Naked DNA Encoding Vascular Endothelial Growth Factor Improves Collateral Flow to Ischemic Myocardium

Tio¹,

Tkebuchava²,

Scheuermann³

et al. 1999

Human Gene Therapy

129

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Both VEGF protein and VEGF DNA in combination with an adenoviral vector have been shown to enhance collateral formation in a porcine model of chronic myocardial ischemia. We sought to determine whether direct intramyocardial injection of naked DNA encoding for VEGF could similarly improve myocardial perfusion. Initially, 23 nonischemic pigs received either 200 microg of plasmid DNA encoding beta-galactosidase (pCMVbeta, n = 11) or 500 microg of phVEGF165 (n = 12) into four separate sites in the myocardium via a small anterolateral thoracotomy incision in the fourth intercostal space. Two additional groups of pigs received an intramyocardial injection of either phVEGF165 (n = 6) or pCMVbeta (n = 7) 3 to 4 weeks after implantation of an ameroid constrictor around the left circumflex coronary artery. The injections caused no change in heart rate or blood pressure, and no ventricular arrhythmias or histologic evidence of inflammation. VEGF protein was detected by Western blot in VEGF-treated animals, with the strongest bands closest to the injection site. Plasma VEGF concentration (ELISA) increased from 3+/-2 to 27+/-13 pg/ml (p = 0.035) by day 4 after treatment. No increase in VEGF protein was noted in pCMVbeta-treated animals whereas these did stain positive for beta-Gal. Resting myocardial blood flow (colored microspheres) was significantly reduced in the ischemic versus nonischemic territory in control animals (1.07+/-0.05 versus 1.32+/-0.05; p < 0.05) but not VEGF-treated pigs (1.32+/-0.24 versus 1.13+/-0.12; p = NS). Maximal vasodilatation with adenosine significantly increased flow to the ischemic region in VEGF-treated pigs (2.16+/-0.57 versus 1.32+/-0.24; p < 0.05) but not controls (1.31+/-0.05 versus 1.17+/-0.06;p = NS). Collateral filling of the occluded circumflex artery improved in five of six VEGF-treated pigs (mean change in Rentrop score, +1.5). We conclude that direct intramyocardial transfection phVEGF165 is safe and capable of producing sufficient VEGF protein to enhance collateral formation and myocardial perfusion. This approach may offer an alternative therapy for patients with intractable myocardial ischemia not amenable to PTCA or CABG.

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Section: Evaluation Of Gene Expressionmentioning

confidence: 99%

Intramyocardial Gene Therapy with Naked DNA Encoding Vascular Endothelial Growth Factor Improves Collateral Flow to Ischemic Myocardium

Tio¹,

Tkebuchava²,

Scheuermann³

et al. 1999

Human Gene Therapy

129

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“…1995). In addition, the inclusion of a polymer carrier (Feldman & Steg 1997, Oswald et al . 1997, Van Belle et al .…”

Section: Methods For Local Delivery Of Genetic Materialsmentioning

confidence: 99%

Local gene delivery to the vessel wall

Smith¹,

Walsh²

2001

Acta Physiologica Scandinavica

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This review will provide an overview of delivery strategies that are being evaluated for vascular gene therapy. We will limit our discussion to those studies that have been demonstrated, utilizing in vivo model systems, to limit post-interventional restenosis. We also discuss the efficacy of the vectors and methods currently being used to transfer genetic material to the vessel wall. The efficiency of these techniques is a critical issue for the successful application of gene therapy.

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