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The study of fetal rat model of intra-amniotic isoproterenol injection induced heart dysfunction and phenotypic switch of contractile proteins.

Li Y, Fang J, Hua Y, Wang C, Mu D, Zhou K - Biomed Res Int (2014)

Bottom Line: Intra-amniotic injections of isoproterenol were supplied on E14.5 and E15.5 for fetuses and 7-day continuous intraperitoneal injections were performed for adults.Isoproterenol twice treated fetuses exhibited significant changes in histological evaluation, and mitochondrial damages were significantly severe with increased apoptotic rate.ANP and BNP increased and that of MMP-2 increased in isoproterenol twice treated group compared to control group, without CTGF.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Cardiovascular Disease, West China Second University Hospital, Sichuan University, No. 20, 3rd Section, South Renmin Road, Chengdu, Sichuan 610041, China.

ABSTRACT
To establish a reliable isoproterenol induced heart dysfunction fetal rat model and understand the switches of contractile proteins, 45 pregnant rats were divided into 15 mg/kg-once, 15 mg/kg-twice, sham-operated once, sham-operated twice, and control groups. And 18 adult rats were divided into isoproterenol-treated and control groups. H&E staining, Masson staining, and transmission electron microscope were performed. Apoptotic rate assessed by TUNEL analysis and expressions of ANP, BNP, MMP-2, and CTGF of hearts were measured. Intra-amniotic injections of isoproterenol were supplied on E14.5 and E15.5 for fetuses and 7-day continuous intraperitoneal injections were performed for adults. Then echocardiography was performed with M-mode view assessment on E18.5 and 6 weeks later, respectively. Isoproterenol twice treated fetuses exhibited significant changes in histological evaluation, and mitochondrial damages were significantly severe with increased apoptotic rate. ANP and BNP increased and that of MMP-2 increased in isoproterenol twice treated group compared to control group, without CTGF. The isoforms transition of troponin I and myosin heavy chain of fetal heart dysfunction were opposite to adult procedure. The administration of intra-amniotic isoproterenol to fetal rats could induce heart dysfunction and the regulation of contractile proteins of fetuses was different from adult procedure.

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mRNA expression of CTGF, MMP-2, ANP, and BNP in control sham-operated and ISO-treated hearts as quantified by real-time PCR. Individual gene expression was normalized to GAPDH mRNA and displayed as a percentage of control. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.0001. n = 9/group.
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fig6: mRNA expression of CTGF, MMP-2, ANP, and BNP in control sham-operated and ISO-treated hearts as quantified by real-time PCR. Individual gene expression was normalized to GAPDH mRNA and displayed as a percentage of control. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.0001. n = 9/group.

Mentions: In contrast to what is previously discussed, ISO-treated hearts did not exhibit clear cardiomyocyte borders, and interstitial connective tissue volume was markedly diminished. To explore this further, we examined myocardial gene expression of CTGF and MMP-2, which would be expected to augment collagen degradation (Figures 6(a) and 6(b)). As compared with control hearts, CTGF expression was unchanged in ISO-treated hearts, whereas MMP-2 expression was significantly (P < 0.05) upregulated. The rapid increase of MMP-2 would be expected to favor collagen turnover and loss, which was consistent with the histological findings in Figure 3.


The study of fetal rat model of intra-amniotic isoproterenol injection induced heart dysfunction and phenotypic switch of contractile proteins.

Li Y, Fang J, Hua Y, Wang C, Mu D, Zhou K - Biomed Res Int (2014)

mRNA expression of CTGF, MMP-2, ANP, and BNP in control sham-operated and ISO-treated hearts as quantified by real-time PCR. Individual gene expression was normalized to GAPDH mRNA and displayed as a percentage of control. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.0001. n = 9/group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4127273&req=5

fig6: mRNA expression of CTGF, MMP-2, ANP, and BNP in control sham-operated and ISO-treated hearts as quantified by real-time PCR. Individual gene expression was normalized to GAPDH mRNA and displayed as a percentage of control. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.0001. n = 9/group.
Mentions: In contrast to what is previously discussed, ISO-treated hearts did not exhibit clear cardiomyocyte borders, and interstitial connective tissue volume was markedly diminished. To explore this further, we examined myocardial gene expression of CTGF and MMP-2, which would be expected to augment collagen degradation (Figures 6(a) and 6(b)). As compared with control hearts, CTGF expression was unchanged in ISO-treated hearts, whereas MMP-2 expression was significantly (P < 0.05) upregulated. The rapid increase of MMP-2 would be expected to favor collagen turnover and loss, which was consistent with the histological findings in Figure 3.

Bottom Line: Intra-amniotic injections of isoproterenol were supplied on E14.5 and E15.5 for fetuses and 7-day continuous intraperitoneal injections were performed for adults.Isoproterenol twice treated fetuses exhibited significant changes in histological evaluation, and mitochondrial damages were significantly severe with increased apoptotic rate.ANP and BNP increased and that of MMP-2 increased in isoproterenol twice treated group compared to control group, without CTGF.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Cardiovascular Disease, West China Second University Hospital, Sichuan University, No. 20, 3rd Section, South Renmin Road, Chengdu, Sichuan 610041, China.

ABSTRACT
To establish a reliable isoproterenol induced heart dysfunction fetal rat model and understand the switches of contractile proteins, 45 pregnant rats were divided into 15 mg/kg-once, 15 mg/kg-twice, sham-operated once, sham-operated twice, and control groups. And 18 adult rats were divided into isoproterenol-treated and control groups. H&E staining, Masson staining, and transmission electron microscope were performed. Apoptotic rate assessed by TUNEL analysis and expressions of ANP, BNP, MMP-2, and CTGF of hearts were measured. Intra-amniotic injections of isoproterenol were supplied on E14.5 and E15.5 for fetuses and 7-day continuous intraperitoneal injections were performed for adults. Then echocardiography was performed with M-mode view assessment on E18.5 and 6 weeks later, respectively. Isoproterenol twice treated fetuses exhibited significant changes in histological evaluation, and mitochondrial damages were significantly severe with increased apoptotic rate. ANP and BNP increased and that of MMP-2 increased in isoproterenol twice treated group compared to control group, without CTGF. The isoforms transition of troponin I and myosin heavy chain of fetal heart dysfunction were opposite to adult procedure. The administration of intra-amniotic isoproterenol to fetal rats could induce heart dysfunction and the regulation of contractile proteins of fetuses was different from adult procedure.

Show MeSH
Related in: MedlinePlus