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Restenosis after balloon angioplasty of coarctation: relationship with ductus arteriosus
1Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan.
Insights
Balloon angioplasty (BA) for coarctation of the aorta (CoA) can lead to restenosis due to smooth muscle cell (SMC) proliferation. This study identifies neointimal formation and SMC changes near the ductus arteriosus (DA) as key mechanisms.
Area of Science:
- Cardiovascular Research
- Pediatric Cardiology
- Vascular Biology
Background:
- Balloon angioplasty (BA) is used for coarctation of the aorta (CoA).
- High restenosis rates in infants after BA for native CoA are observed.
- Mechanisms causing restenosis, particularly in relation to ductus arteriosus (DA) tissue properties, remain unclear.
Purpose of the Study:
- To investigate the cause of restenosis following BA in a coarctation of the aorta (CoA) model.
- To examine the transformation of smooth muscle cell (SMC) phenotypes using immunohistologic studies.
Main Methods:
- A surgical CoA model was created in 15 newborn pigs.
- BA was performed one month after initial surgery.
- Immunohistologic studies using SMC myosin heavy chain (MHC) isoform antibodies (SM1, SM2, SMemb) were conducted on aortic tissue at 1 and 3 months post-BA.
Main Results:
- In the neointima, only SMemb was positive, indicating undifferentiated SMCs.
- In the SMC layer of the DA, only SM2 was positive.
- One month post-BA, SM2 was strongly positive in the external tunica media layer around the DA origin.
Conclusions:
- Obstructive neointimal formation from undifferentiated SMC proliferation, triggered by BA, is a primary cause of restenosis.
- SMC proliferation in the external layer around the DA, indicated by SM2 positivity, represents a potential second mechanism for restenosis.
Background:
Recently, balloon angioplasty (BA) has been used for the treatment of coarctation of the aorta (CoA) and the effectiveness of this treatment has been reported. However, the restenosis rate following BA in native CoA in the infant is high and the cause may be related to tissue properties at the origin of the ductus arteriosus (DA). However, the mechanisms responsible for restenosis remain uncertain.
Methods/Results:
The present study was designed to examine transformation of the smooth muscle cell (SMC) phenotypes using immunohistologic studies and to investigate the cause of restenosis of CoA following BA. A CoA model was surgically created in 15 newborn pigs (10-14-days-old; 2.4-4.1 kg). Balloon angioplasty was performed 1 month after the initial operation. One or 3 months after BA, animals were killed and immunohistologic studies on smooth muscle cell (SMC) antibodies against SM1, SM2 and SMemb of the myosin heavy chain (MHC) isoform were performed in the aorta at the CoA and DA. In the neointima, only SMemb was positive. In the SMC layer of the DA, only SM2 was positive. One month after BA, the external layer of the tunica media was strongly positive for SM2 only in the area around the origin of the DA.
Conclusions:
The first cause of restenosis is obstructive neointimal formation caused by the proliferation of undifferentiated SMC into the subendothelial tissue. This proliferation seems to be triggered by BA. The distribution of SM2 1 month after balloon angioplasty showed a similar pattern of proliferation of SMC in the external layer around the DA. This may represent a second mechanism of restenosis.
