Pregnancy Differentially Regulates the Collagens Types I and III in Left Ventricle from Rat Heart (original) (raw)
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Experimental Biology and Medicine, 2018
Pregnancy creates a condition of cardiac volume overload which leads to physiological eccentric hypertrophy of the heart that is reversed in the postpartum period. Pathological cardiac changes in non-pregnant animals are associated with extracellular matrix remodeling. Based on preliminary microarray findings in the hearts of non-pregnant, pregnant, and postpartum mice, we hypothesized that changes in the expression of extracellular matrix protein genes would accompany functional changes in the heart that occur with reproductive status. Adult left ventricle parameters were evaluated by echocardiography in C57BL/6 mice at diestrous (virgin), and at pregnancy days (eds) 10, 12, and 18/19, and at postpartum days (ppds) 1.5 and 7. Twenty-one left ventricle mRNAs were evaluated including genes for tissue inhibitor of metalloproteinases (Timps), several matrix metallopeptidases (Mmps), collagens (Cols), proteoglycans, and enzymes involved in matrix remodeling at similar days except ed10. ...
Increased collagen deposition in the heart of chronically hypoxic ovine fetuses
Journal of Developmental Origins of Health and Disease, 2013
This study determined the effect of chronic intrauterine hypoxia on collagen deposition in the fetal sheep heart. Moderate or severe hypoxia was induced by placental embolization in chronically catheterized fetal sheep for 15 days starting at gestational day 116 6 2 (term ,147 days). The fetal right and left ventricle were evaluated for collagen content using a Sirius red dye and for changes in signaling components of pathways involved in collagen synthesis and remodeling using quantitative polymerase chain reaction and Western blot. In severely hypoxic fetuses (n 5 6), there was a two-fold increase (P , 0.05) in the percentage staining for collagen in the right ventricle, compared with control (n 5 6), whereas collagen content was not altered in the moderate group (n 5 4). Procollagen I and III mRNA levels were increased in the right ventricle, two-fold (P , 0.05) and three-fold (P , 0.05), respectively, in the severe group relative to control. These changes were paralleled by a two-fold increase (P , 0.05) in mRNA levels of the pro-fibrotic cytokine, transforming growth factor b (TGF-b 1 ), in the right ventricle. In the right ventricle, the mRNA levels of matrix metalloproteinase 2 (MMP-2) and its activator, membrane-type MMP (MTI-MMP) were increased five-fold (P 5 0.06) and three-fold (P , 0.05), respectively, relative to control. Protein levels of TGF-b were increased in the left ventricle (P , 0.05). Thus, up-regulated collagen synthesis leading to increased collagen content occurs in the chronically hypoxic fetal heart and may contribute to the right ventricular diastolic and systolic dysfunction reported in human intrauterine growth restriction fetuses.
European Heart Journal, 2011
Aortic stenosis induces pressure overload and myocardial remodelling with concentric hypertrophy and alterations in extracellular matrix (ECM). Aortic valve replacement leads to reverse remodelling, a process of which knowledge is scarce. The aims of the present study were to examine alterations in myocardial gene expression and subsequently identify molecular alterations important for the early phase of reverse remodelling. After 4 weeks of ascending aortic banding, mice were subjected to a debanding operation (DB) and followed for 3, 7, or 14 days. Cardiac function was assessed by echocardiography/tissue Doppler ultrasonography. Myocardial gene expression was examined using Affymetrix microarray and the topGO software and verified by real-time polymerase chain reaction. Quantitative measurements of collagen subtypes were performed. Aortic banding increased left ventricular mass by 60%, with normalization to sham level 14 days after DB. Extracellular matrix genes were the most regulated after DB. Three days after DB, collagen I was transiently increased, whereas collagens III and VIII increased later at 7 days. The ECM genes were the most altered during reverse remodelling. There was a change in isoform constitution as collagen type I increased transiently at 3 days followed by a later increase in types III and VIII at 7 days after DB. This might be important for the biomechanical properties of the heart and recovery of cardiac function.
Molecular and Functional Signature of Heart Hypertrophy During Pregnancy
Circulation Research, 2005
During pregnancy, the heart develops a reversible physiological hypertrophic growth in response to mechanical stress and increased cardiac output; however, underlying molecular mechanisms remain unknown. Here, we investigated pregnancy-related changes in heart structure, function, and gene expression of known markers of pathological hypertrophy and cell stretching in mice hearts. In late pregnancy, hearts show eccentric hypertrophy, as expected for a response to volume overload, with normal left ventricular diastolic function and a moderate reduction in systolic function. Pregnancy-related physiological heart hypertrophy does not induce expression changes of known markers of pathological hypertrophy like: ␣and -myosin heavy chain, atrial natriuretic factor, phospholamban, and sarcoplasmic reticulum Ca 2ϩ -ATPase. Instead, it induces the remodeling of Kv4.3 channel and increased c-Src tyrosine kinase activity, a stretch-responsive kinase. Cardiac Kv4.3 channel gene expression was downregulated by Ϸ3to 5-fold, both at the mRNA and protein levels, and was paralleled by a reduction in transient outward K ϩ currents, a longer action potential and by prolongation of the QT interval. Downregulation of cardiac Kv4.3 transcripts was mimicked by estrogen treatment in ovariectomized mice, and was prevented by the estrogen receptor antagonist ICI 182,780. c-Src activity increased by Ϸ2-fold in late pregnancy and after estrogen treatment. We propose that, in addition to mechanical stress, the rise of estrogen toward the end of pregnancy contributes to pregnancy-related heart hypertrophy by increased c-Src activity and that the rise of estrogen is one factor that down regulates cardiac Kv4.3 gene expression providing a molecular correlate for a longer QT interval in pregnancy. (Circ Res. 2005;96:1208-1216.) Key Words: heart hypertrophy Ⅲ pregnancy Ⅲ estrogen Ⅲ I to Ⅲ
Medicina, 2019
Background and objectives: Cardiac remodeling in pregnancy and postpartum is poorly understood. The aim of this study was to evaluate changes in cardiac fibrosis (pericardial, perivascular, and interstitial), as well as the expression of matrix metalloproteinases (MMP-1, MMP-2, and MMP-9) and their inhibitors (Tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-4) during late pregnancy and postpartum in rat left ventricle. Materials and Methods: Female Sprague–Dawley rats were used for this study. Rats were divided three groups: non-pregnant, late pregnancy, and postpartum. The heart was weighed and cardiac fibrosis was studied by conventional histological procedures. The expression and transcript level of target proteins were evaluated using immunoblot techniques and quantitative PCR. Results: The experiments showed an increase of perivascular, pericardial, and interstitial fibrosis in heart during pregnancy and its reversion in postpartum. Moreover, in late pregnancy, MMP-1, ...
Collagen type VI expression during cardiac development and in human fetuses with trisomy 21
The Anatomical Record, 2003
The role played by specific extracellular matrix molecules in normal endocardial cushion differentiation into valves and septa remains to be established. In this respect, type collagen VI is of particular interest because genes encoding the α1 and α2 chains are located on chromosome 21, and defects involving the atrioventricular (AV) cushions are frequent in trisomy 21. Collagen VI expression was studied in normal human embryonic and fetal hearts (5–18 weeks of development) and compared by immunohistochemistry with results from fetuses (10–16 weeks of development) with trisomy 21. During normal endocardial cushion differentiation (5–8 weeks) there was marked collagen VI expression in the AV cushions, whereas only minor expression was seen in the outflow tract cushions. In the normal fetuses (10–18 weeks), collagen VI in the AV cushions had condensed into a marked zone on the atrial side of the leaflets, as well as subendocardially in other regions of high shear stress. Morphological defects involving the endocardial cushion-derived structures were present in all trisomy 21 cases. An abnormally large membranous septum was observed in three cases. An AV septal defect (AVSD) was present in two, while one had a ventricular septal defect (VSD). Two cases presented with a secondary atrial septal defect (ASDII), and one had an AVSD. Mild to moderate valve dysmorphia was found in all cases. Collagen VI staining in trisomy 21 was more intense than in the normal subjects; however, there were no differences in the spatial expression patterns. We conclude that collagen VI is expressed in the AV cushions and persists during valve differentiation. Collagen VI is more prominent in fetal trisomy 21 hearts than in normal hearts. We hypothesise that collagen VI has a role in the development of heart defects involving endocardial cushion differentiation—specifically in the AV canal, the most common site of malformations affecting children with trisomy 21. Anat Rec Part A 275A:1109–1116, 2003. © 2003 Wiley-Liss, Inc.
Expression of Type XVII Collagen .ALPHA.1 Chain mRNA in the Mouse Heart
Japanese Heart Journal, 1998
The type X\'II collagen al chain has been identified as a component of the type I hemidesmosome, and is thus thought to play a role in extracellular matrix ECM maintenance and signal transduction between the cell and the EC\I. We examined the expression of type XVII collagen al chain mRNA in the mouse heart by Northern blot analysis and determined the sequential changes of its expression in different developmental stages of the heart using the reverse transcriptase-polymerase chain reaction (RT-PCR) method..Vorthem blotting: Total RNA was extracted from 10 adult mouse hearts by the guanidine/cesium method. Hybridization was performed with mouse cDNA for a1 XVIL collagen. RT-PCP,• Total RNA was extracted from 7 embryos. 4 neonates and 8 adult mice. Reverse transcription was performed using oligo-dT primer and \I\ILV. Amplification was carried out in a1 XVIIi collagen and glyceraldehyde 3-phosphate dehvdrogenase (GAPDH). GAPDH served as an internal control. Northern blotting revealed a 5.6 kb signal that was identical to that of the a1 XVII) of skin and transformed keratinocyte reported previously. The sequences of the PCR products were also identical to those reported. The normalized expression ratios of al XVII) were 0.91 ± 0.20 in the embryonic heart, 0.36 ± 0.20 in the neonatal heart and 0.96 ± 0.21 in the adult heart. In conclusion, we identified the expression of type XVII collagen al chain mRNA in the mouse heart, suggesting that the type I hemidesmosome is located in the heart. The results of the RT-PCR at different developmental stages of the heart suggest that type XVII collagen contributes not only to cardiogenesis in the embryonic stage but also to maintenance of architecture and function in the adult heart.
New frontiers in heart hypertrophy during pregnancy
American journal of cardiovascular disease, 2012
During Pregnancy, heart develops physiological left ventricular hypertrophy as a result of the natural volume overload. Previously we have characterized the molecular and functional signature of heart hypertrophy during pregnancy. Cardiac hypertrophy during pregnancy is a complex process that involves many changes including in the signalling pathways, composition of extracellular matrix as well as the levels of sex hormones. This review summarises the recent advances and the new frontiers in the context of heart hypertrophy during pregnancy. In particular we focus on structural and extracellular matrix remodelling as well as signalling pathways in pregnancy-induced physiological heart hypertrophy. Emerging evidence shows that various microRNAs modulate key components of hypertrophy, therefore the role of microRNAs in the regulation of gene expression in pregnancy induced hypertrophy is also discussed. We also review the role of ubiquitin proteasome system, the major machinery for th...