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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 mRNA is significantly lower in iVSD hearts compared to control hearts.Quantitative RT-PCR was used to analyze message levels of YAP1 in iVSD and control hearts. Our results indicate that YAP1 is significantly decreased in iVSD samples compared to normal controls. GAPDH served as a control. Bars indicate means ± SD. The Student’s t _test was performed to evaluate statistical significance, iVSD group: n = 20; control group: n = 6, ***p<0.001.
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pone.0139712.g003: YAP1 mRNA is significantly lower in iVSD hearts compared to control hearts.Quantitative RT-PCR was used to analyze message levels of YAP1 in iVSD and control hearts. Our results indicate that YAP1 is significantly decreased in iVSD samples compared to normal controls. GAPDH served as a control. Bars indicate means ± SD. The Student’s t _test was performed to evaluate statistical significance, iVSD group: n = 20; control group: n = 6, ***p<0.001.

Mentions: To assess whether there was a decrease in YAP1 mRNA expression, total RNA from both iVSD and normal hearts was extracted and measured using qRT-PCR analysis. The results showed that YAP1 relative mRNA levels (Fig 3) in iVSD hearts were decreased compared to normal hearts (1.03±0.0674 in iVSD hearts compared to 3.274±0.4951 in normal hearts, p<0.001; normal heart/iVSD heart ratio = 3.074). The results from the qRT-PCR analysis indicated that YAP1 gene expression was significantly reduced in iVSD patients resulting in lower protein levels and suggested that the decrease in YAP1 was associated with the incidence of iVSDs in patients.


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 mRNA is significantly lower in iVSD hearts compared to control hearts.Quantitative RT-PCR was used to analyze message levels of YAP1 in iVSD and control hearts. Our results indicate that YAP1 is significantly decreased in iVSD samples compared to normal controls. GAPDH served as a control. Bars indicate means ± SD. The Student’s t _test was performed to evaluate statistical significance, iVSD group: n = 20; control group: n = 6, ***p<0.001.
© Copyright Policy
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4591351&req=5

pone.0139712.g003: YAP1 mRNA is significantly lower in iVSD hearts compared to control hearts.Quantitative RT-PCR was used to analyze message levels of YAP1 in iVSD and control hearts. Our results indicate that YAP1 is significantly decreased in iVSD samples compared to normal controls. GAPDH served as a control. Bars indicate means ± SD. The Student’s t _test was performed to evaluate statistical significance, iVSD group: n = 20; control group: n = 6, ***p<0.001.
Mentions: To assess whether there was a decrease in YAP1 mRNA expression, total RNA from both iVSD and normal hearts was extracted and measured using qRT-PCR analysis. The results showed that YAP1 relative mRNA levels (Fig 3) in iVSD hearts were decreased compared to normal hearts (1.03±0.0674 in iVSD hearts compared to 3.274±0.4951 in normal hearts, p<0.001; normal heart/iVSD heart ratio = 3.074). The results from the qRT-PCR analysis indicated that YAP1 gene expression was significantly reduced in iVSD patients resulting in lower protein levels and suggested that the decrease in YAP1 was associated with the incidence of iVSDs in patients.

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