Therapeutic Angiogenesis: Protein and Gene Therapies offer Hope to Patients with Myocardial Ischemia Ryan McAuley Dept. of Biology Furman University Greenville, SC Palo Alto Veterans Affairs Healthcare System Stanford University School of Medicine Department of Cardiology Outline
Dept. of Biology
-Stenosis of coronary arteries
-CABG and PCI
-Targets: endothelial cells, smooth muscle cells, fibroblasts, myocytes, and some tumor cells
-Targets endothelial cells exclusively
-stabilization of mRNA coding
-increased transcription due to activation of Hypoxia-Inducible Factor-1 (HIF-1) in the promoter region of VEGF
Endothelial Cell Response
-size and number of vessels
-measurement of coronary blood flow
-quantitation of endothelial cell markers
ST segment depression
-Protein Therapy Vs. Gene Therapy
-Phase I to determine safety/feasibility
-All subsequent phases must include placebo group to determine efficacy
-recombinant form of FGF or VEGF
-VEGF or FGF inserted into a viral vector
-Naked DNA plasmid encoding for transcription of VEGF or FGF
Characteristic Hope to Patients with Myocardial Ischemia
More likely Less likely
Easier Potential risk for inflammatory response if viral vector used
but high level but low level
Exposure to GF
Need for repeat dose
Exposure to foreign genetic material
-number of viral particles
-DNA plasmids in units of µg
-No significant improvement in exercise time or stress nuclear perfusion imaging at 90 days
-Less angina in treatment group (P=0.057)
-Trend toward greater improvement in older and more symptomatic pts.
Special thanks to Dr. Thompson for her support and guidance through this entire project.
To Victor Froelicher, MD and Jonathan Myers, PhD for allowing me the opportunity to work with them and for their help with my paper.
To my uncle Paul McAuley, PhD for the “referral” to the aforementioned Docs.
To Soon-to-be-Dr. Schammel for her encouragement and technological assistance.
To Dr. Turgeon for her help and enthusiasm.
And finally, to Dean Charles Brock, PhD for allowing Furman students the opportunity to participate in internships such as these through Furman Advantage funding.