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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

Downstream targets of YAP1 are significantly lower in iVSD hearts compared to control hearts.GAPDH served as a control. (A) CTGF and AXL relative mRNA levels were significantly lower in iVSD compared to control subjects. GAPDH served as a control. Data presented as means ± SD. The Student’s t-test was performed to evaluate statistical significance, iVSD group: n = 20, control group: n = 6, **p<0.01.
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pone.0139712.g004: Downstream targets of YAP1 are significantly lower in iVSD hearts compared to control hearts.GAPDH served as a control. (A) CTGF and AXL relative mRNA levels were significantly lower in iVSD compared to control subjects. GAPDH served as a control. Data presented as means ± SD. The Student’s t-test was performed to evaluate statistical significance, iVSD group: n = 20, control group: n = 6, **p<0.01.

Mentions: Since YAP1 was significantly reduced in iVSD hearts, we analyzed the expression of its downstream targets. Here we measured gene expression levels of two frequently used markers of YAP1 activity: CTGF and AXL [10–12]. As expected, the expression of both CTGF and AXL were downregulated (Fig 4). These results showed that both YAP1 and its downstream targets were reduced in iVSD hearts compared to normal hearts.


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)

Downstream targets of YAP1 are significantly lower in iVSD hearts compared to control hearts.GAPDH served as a control. (A) CTGF and AXL relative mRNA levels were significantly lower in iVSD compared to control subjects. GAPDH served as a control. Data presented as means ± SD. The Student’s t-test was 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.g004: Downstream targets of YAP1 are significantly lower in iVSD hearts compared to control hearts.GAPDH served as a control. (A) CTGF and AXL relative mRNA levels were significantly lower in iVSD compared to control subjects. GAPDH served as a control. Data presented as means ± SD. The Student’s t-test was performed to evaluate statistical significance, iVSD group: n = 20, control group: n = 6, **p<0.01.
Mentions: Since YAP1 was significantly reduced in iVSD hearts, we analyzed the expression of its downstream targets. Here we measured gene expression levels of two frequently used markers of YAP1 activity: CTGF and AXL [10–12]. As expected, the expression of both CTGF and AXL were downregulated (Fig 4). These results showed that both YAP1 and its downstream targets were reduced in iVSD hearts compared to normal hearts.

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