Abstract 14865: Intravenous Injection of Liposome-Based Nanoparticles Containing a Novel Prostacyclin Analogue Selectively Targets Ischemia-Reperfused Myocardium to Enhance Angiogenesis and Functional Recovery in Rat
Introduction: Treatment for ischemia reperfusion (I/R) myocardial injury has not been fully established. Nanoparticles (NP) are proposed as an efficient drug delivery system for I/R organ injury. We hypothesized YS-1301, a synthetic prostacyclin analogue, incorporated liposome-based NP (YS-1301NP) may attenuate I/R myocardial injury.
Methods: Adult male Sprague-Dawley rats underwent 30 minutes’ occlusion of the left coronary artery, while YS-1301NP, NP only or PBS were intravenously injected at 5 minutes before the reperfusion (n=10 each).
Results: The 11.7-T magnetic resonance imaging displayed a selective accumulation of gadolinium (Gd)-labeled liposome in the ischemic area at 24 hours after the NP injection (Figure A), while the confocal microscopy showed a predominant presence of fluorescent-labeled liposome in the ischemic area compared to that of the non-ischemic area (615±206 /mm2 vs 56±35 /mm2, P <0.001, Figure B). The YS-1301 level was significantly higher in the heart (4.9±4.9 ng/g) than the plasma (1.6±1.2 ng/g) with a peak at 24 hours. As a result, infarct size in the area at risk of infarction at 24 hours was significantly smaller in the YS-1301NP group (11±10%) than that in the NP only (24±8%) or the PBS (30±15%) groups. Moreover, ejection fraction at 24 hours was significantly greater in the YS-1301NP group (48±8%) than that in the NP-only (39±6%) or the PBS (37±6%) groups (P <0.01). In addition, expression of hepatocyte growth factor, platelet derived growth factor β or stromal cell derived factor 1 in the ischemic area was significantly higher in the YS-1301NP group than that in the NP only or the PBS groups, while CD31-positive capillary density in the ischemic area was significantly greater in the YS-1301NP group (133±15 /mm2, P <0.01) than that in the NP (104±12 /mm2) only or the PBS group (95±13 /mm2).
Conclusion: Intravenously injected YS-1301NP was selectively delivered into the I/R myocardium, protecting from the injury via proangiogenic effects.
Author Disclosures: S. Yajima: None. S. Miyagawa: None. S. Fukushima: None. Y. Sakai: None. A. Harada: None. H. Iseoka: None. M. Shiozaki: None. Y. Mori: None. Y. Yoshioka: None. Y. Sawa: None.
- © 2016 by American Heart Association, Inc.