Author + information
- Hideki Miyachia,b,
- Shuhei Taraa,b,
- Tadahisa Sugiuraa,b,
- Tai Yia,b,
- Yong-Ung Leea,b,
- Avion Y. Leea,b,
- Shinka Miyamotoa,b,
- Toshihiro Shojia,b,
- Christopher K. Breuera,b and
- Toshiharu Shinokaa,b
Background: Macrophages are the primary cell types orchestrating tissue engineered vascular graft (TEVG) extracellular matrix (ECM) formation and infiltrate into the TEVG from three sources: the anastomosis, the circulating blood, and transmural migration. However, the the primary source of macrophage infiltrating into the TEVG remains to be elucidated. To fully elucidate the mechanism of TEVG ECM formation, we developed two arterial TEVGs models selectively inhibit the location of cell infiltration and investigated macrophage effects on TEVG ECM formation.
Methods: Two different TEVGs were constructed: 1) Outer electrospun (OES) TEVG to inhibit transmural cell infiltration and, 2) Inner electrospun (IES) TEVG to inhibit circulating cell infiltration. The TEVGs were implanted in mice infrarenal abdominal aortas and evaluated for 4 and 8 weeks (n=5 and n=10 per group, respectively).
Results: Immunohistochemistry revealed macrophage numbers continually increased for 8 weeks in the OES TEVG (0.44±0.38 x103/ mm2 vs. 1.09±0.70 x103/mm2, 4 vs. 8 weeks, p<0.001), but peaked at 4 weeks for the IES TEVG (1.01±0.53 x103/mm2 vs. 0.84±0.55 x103/ mm2, p=0.02). In addition, only M1 macrophages continually increased in the OES TEVG (0.35±0.39x103/mm2 vs. 0.77±0.61x103/mm2, p<0.001), whereas, they peaked at 4 weeks in the IES TEVG (0.70±0.37x103/mm2 vs. 0.52±0.41x103/mm2, p=0.015). M2 macrophages in both grafts were similar between 4 and 8 weeks. RT-PCR also reflected these results. Polarizing microscope images showed that the OES TEVG displayed less collagen content than the IES TEVG (%area: 2.9±1.6% vs. 7.3±3.9%, p=0.019). In the OES TEVG, the majority of collagen changed from type III (immature) at 4 weeks to type I (mature) at 8 weeks (type I vs III; 0.4±0.4% vs. 1.5±1.4%, p=0.29 at 4 weeks, 2.8±1.5% vs. 0.2±0.1%, p<0.001 at 8 weeks). However, the majority in the IES Graft was already type I by 4 weeks (2.5±1.5% vs. 1.0±0.5%, p=0.09 at 4 weeks, 6.5±3.9% vs. 0.8±1.1%, p<0.001 at 8 weeks).
Conclusions: IES TEVGs turned off inflammation reaction in a shorter time and promoted more ECM formation than OES TEVGs. Transmural macrophage migration is possibly the primary cell population that promotes ECM formation.
Poster Hall, Hall C
Saturday, March 18, 2017, 9:45 a.m.-10:30 a.m.
Session Title: Cutting Edge Vascular Medicine
Abstract Category: 38. Vascular Medicine: Basic
Presentation Number: 1205-356
- 2017 American College of Cardiology Foundation