HealthDay News – The amplitude of therapeutic revascularization associated with recombinant adeno-associated virus (rAAV) (5 × 1012 viral particles encoding thymosin beta 4 [Tβ4]) is reduced with diabetes mellitus, according to an experimental study published in the Journal of the American College of Cardiology.
Rabea Hinkel, DVM, from the Technical University of Munich, and colleagues obtained myocardial samples from patients with end-stage heart failure, and used diabetic and wild-type (wt) pigs to analyze myocardial vascularization and function. The authors introduced chronic ischemia percutaneously in the circumflex artery on day 0. At day 28, they applied rAAV (5 × 1012 viral particles encoding vascular endothelial growth factor-A or rAAV.Tβ4) regionally.
The researchers found that, compared with nondiabetic explants, diabetic human myocardial explants revealed capillary rarefaction and pericyte loss. In diabetic pigs, hyperglycemia induced capillary rarefaction in the myocardium, even without ischemia, concomitant with a distinct loss of ejection fraction (EF). In chronic ischemic hearts, capillary density further decreased, as did EF. Capillary density and maturity were enhanced in diabetic hearts less efficiently than in wt hearts following treatment with rAAV.Tβ4, similar to collateral growth. rAAV.Tβ4 improved EF in diabetic hearts, but to a lesser extent than in wt hearts.
“Diabetes mellitus destabilized microvascular vessels of the heart, affecting the amplitude of therapeutic neovascularization via rAAV.Tβ4 in a translational large animal model of hibernating myocardium,” the authors wrote.
Disclosures: One author filed and licensed patent applications on microRNA biomarkers.
- Hinkel R, Hoewe A, Renner S, et al. Diabetes mellitus-induced microvascular destabilization in the myocardium. J Am Coll Cardiol. 2017;69(2):131-143. doi:10.1016/j.jacc.2016.10.058
- Ishikawa K. The transgenic diabetic pig heart. A “sweet heart” for translational cardiovascular research. J Am Coll Cardiol. 2017;69(2):144-146. doi:10.1016/j.jacc.2016.11.018