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Decreased Yes-Associated Protein-1 (YAP1) Expression in Pediatric Hearts with Ventricular Septal Defects.

Ye L, Yin M, Xia Y, Jiang C, Hong H, Liu J - PLoS ONE (2015)

Bottom Line: Animal studies have suggested that the downregulation of Yes-associated protein 1 (YAP1) during embryonic development causes VSD-associated CHDs.However, how YAP1 contributes to isolated VSD (iVSD) is unclear.Concomitantly, mRNA levels of YAP1 downstream targets CTGF and AXL were also significantly decreased in iVSD specimens.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China; Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Pediatric Congenital Heart Disease Institute, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.

ABSTRACT

Background: Ventricular septal defects (VSDs) are the most common and simplest type of congenital heart diseases (CHDs). Animal studies have suggested that the downregulation of Yes-associated protein 1 (YAP1) during embryonic development causes VSD-associated CHDs. However, how YAP1 contributes to isolated VSD (iVSD) is unclear.

Methods and results: Twenty right atrial specimens were obtained from iVSD patients during routine congenital cardiac surgery and we assessed YAP1 expression in these specimens. For controls, six right atrial specimens were obtained from normal hearts of children without heart disease, three of whom died from cerebral palsy, and three who underwent heart transplants. YAP1 mRNA and protein levels and nuclear localization were significantly reduced in iVSD specimens compared to normal heart specimens. Concomitantly, mRNA levels of YAP1 downstream targets CTGF and AXL were also significantly decreased in iVSD specimens. Although Ki67-positive cardiomyocytes in iVSD specimens were comparable to normal heart specimens, Ki67-positive non-cardiomyocytes were significantly decreased.

Conclusions: YAP1 expression was markedly decreased in hearts of iVSD children. Given the important role of YAP1 during heart development, downregulation of YAP1 expression may contribute to iVSD and affect the proliferation of non-cardiomyocytes.

No MeSH data available.


Related in: MedlinePlus

YAP1 protein expression is decreased in atrial tissue derived from iVSD patients.(A)Western blot analysis of resolved atrial tissues from control and iVSD hearts demonstrates that YAP1 is significantly decreased in iVSD hearts. (B) Numeric data obtained by densitometry analysis using GAPDH as a loading control. Data presented as means ± SDs. Student’s t-tests were performed to evaluate statistical significance (iVSD group: n = 20; control group: n = 6); **p < 0.01.
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pone.0139712.g001: YAP1 protein expression is decreased in atrial tissue derived from iVSD patients.(A)Western blot analysis of resolved atrial tissues from control and iVSD hearts demonstrates that YAP1 is significantly decreased in iVSD hearts. (B) Numeric data obtained by densitometry analysis using GAPDH as a loading control. Data presented as means ± SDs. Student’s t-tests were performed to evaluate statistical significance (iVSD group: n = 20; control group: n = 6); **p < 0.01.

Mentions: To analyze YAP1 protein levels, tissue extracts from iVSD (n = 20) and normal atria (n = 6) were analyzed using Western blots. The results demonstrated that YAP1 protein levels in iVSD hearts were significantly decreased compared with normal hearts (Fig 1A and 1B; p < 0.01).


Decreased Yes-Associated Protein-1 (YAP1) Expression in Pediatric Hearts with Ventricular Septal Defects.

Ye L, Yin M, Xia Y, Jiang C, Hong H, Liu J - PLoS ONE (2015)

YAP1 protein expression is decreased in atrial tissue derived from iVSD patients.(A)Western blot analysis of resolved atrial tissues from control and iVSD hearts demonstrates that YAP1 is significantly decreased in iVSD hearts. (B) Numeric data obtained by densitometry analysis using GAPDH as a loading control. Data presented as means ± SDs. Student’s t-tests were performed to evaluate statistical significance (iVSD group: n = 20; control group: n = 6); **p < 0.01.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4591351&req=5

pone.0139712.g001: YAP1 protein expression is decreased in atrial tissue derived from iVSD patients.(A)Western blot analysis of resolved atrial tissues from control and iVSD hearts demonstrates that YAP1 is significantly decreased in iVSD hearts. (B) Numeric data obtained by densitometry analysis using GAPDH as a loading control. Data presented as means ± SDs. Student’s t-tests were performed to evaluate statistical significance (iVSD group: n = 20; control group: n = 6); **p < 0.01.
Mentions: To analyze YAP1 protein levels, tissue extracts from iVSD (n = 20) and normal atria (n = 6) were analyzed using Western blots. The results demonstrated that YAP1 protein levels in iVSD hearts were significantly decreased compared with normal hearts (Fig 1A and 1B; p < 0.01).

Bottom Line: Animal studies have suggested that the downregulation of Yes-associated protein 1 (YAP1) during embryonic development causes VSD-associated CHDs.However, how YAP1 contributes to isolated VSD (iVSD) is unclear.Concomitantly, mRNA levels of YAP1 downstream targets CTGF and AXL were also significantly decreased in iVSD specimens.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China; Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Pediatric Congenital Heart Disease Institute, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.

ABSTRACT

Background: Ventricular septal defects (VSDs) are the most common and simplest type of congenital heart diseases (CHDs). Animal studies have suggested that the downregulation of Yes-associated protein 1 (YAP1) during embryonic development causes VSD-associated CHDs. However, how YAP1 contributes to isolated VSD (iVSD) is unclear.

Methods and results: Twenty right atrial specimens were obtained from iVSD patients during routine congenital cardiac surgery and we assessed YAP1 expression in these specimens. For controls, six right atrial specimens were obtained from normal hearts of children without heart disease, three of whom died from cerebral palsy, and three who underwent heart transplants. YAP1 mRNA and protein levels and nuclear localization were significantly reduced in iVSD specimens compared to normal heart specimens. Concomitantly, mRNA levels of YAP1 downstream targets CTGF and AXL were also significantly decreased in iVSD specimens. Although Ki67-positive cardiomyocytes in iVSD specimens were comparable to normal heart specimens, Ki67-positive non-cardiomyocytes were significantly decreased.

Conclusions: YAP1 expression was markedly decreased in hearts of iVSD children. Given the important role of YAP1 during heart development, downregulation of YAP1 expression may contribute to iVSD and affect the proliferation of non-cardiomyocytes.

No MeSH data available.


Related in: MedlinePlus