Cardiac Remodeling During Pregnancy With Metabolic Syndrome: Prologue of Pathological Remodeling
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PROVIDER: PRJNA993651 | ENA |
REPOSITORIES: ENA
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Project description:The heart undergoes physiological hypertrophy during pregnancy in healthy individuals. Metabolic syndrome (MetS) is now prevalent in women of child-bearing age and might add risks of adverse cardiovascular events during pregnancy. The present study asks if cardiac remodeling during pregnancy in obese individuals with MetS is abnormal and whether this predisposes them to a higher risk for cardiovascular disorders. The idea that MetS induces pathological cardiac remodeling during pregnancy was studied in a long-term (15 weeks) Western diet–feeding animal model that recapitulated features of human MetS. Pregnant female mice with Western diet (45% kcal fat)–induced MetS were compared with pregnant and nonpregnant females fed a control diet (10% kcal fat). Pregnant mice fed a Western diet had increased heart mass and exhibited key features of pathological hypertrophy, including fibrosis and upregulation of fetal genes associated with pathological hypertrophy. Hearts from pregnant animals with WD-induced MetS had a distinct gene expression profile that could underlie their pathological remodeling. Concurrently, pregnant female mice with MetS showed more severe cardiac hypertrophy and exacerbated cardiac dysfunction when challenged with angiotensin II/phenylephrine infusion after delivery. These results suggest that preexisting MetS could disrupt physiological hypertrophy during pregnancy to produce pathological cardiac remodeling that could predispose the heart to chronic disorders.
2023-07-13 | GSE237063 | GEO
Project description:BackgroundThe heart undergoes physiological hypertrophy during pregnancy in healthy individuals. Metabolic syndrome (MetS) is now prevalent in women of child-bearing age and might add risks of adverse cardiovascular events during pregnancy. The present study asks if cardiac remodeling during pregnancy in obese individuals with MetS is abnormal and whether this predisposes them to a higher risk for cardiovascular disorders.MethodsThe idea that MetS induces pathological cardiac remodeling during pregnancy was studied in a long-term (15 weeks) Western diet-feeding animal model that recapitulated features of human MetS. Pregnant female mice with Western diet (45% kcal fat)-induced MetS were compared with pregnant and nonpregnant females fed a control diet (10% kcal fat).ResultsPregnant mice fed a Western diet had increased heart mass and exhibited key features of pathological hypertrophy, including fibrosis and upregulation of fetal genes associated with pathological hypertrophy. Hearts from pregnant animals with WD-induced MetS had a distinct gene expression profile that could underlie their pathological remodeling. Concurrently, pregnant female mice with MetS showed more severe cardiac hypertrophy and exacerbated cardiac dysfunction when challenged with angiotensin II/phenylephrine infusion after delivery.ConclusionsThese results suggest that preexisting MetS could disrupt physiological hypertrophy during pregnancy to produce pathological cardiac remodeling that could predispose the heart to chronic disorders.
| S-EPMC7888689 | biostudies-literature
Project description:Impaired extracellular matrix (ECM) remodeling is a hallmark of many chronic inflammatory disorders that can lead to cellular dysfunction, aging, and disease progression. The ECM of the aged heart and its effects on cardiac cells during chronological and pathological aging are poorly understood across species. Here, we used mass spectrometry-based proteomics to quantitatively characterize age-related remodeling of the left ventricle (LV) of mice and humans during chronological and pathological (Hutchinson-Gilford progeria syndrome (HGPS)) aging. Of the approximately 300 ECM proteins quantified, we identified 13 proteins that were increased, including lactadherin (MFGE8), collagen VI 6 (COL6A6), vitronectin (VTN) and immunoglobulin heavy constant mu (IGHM), whereas fibulin-5 (FBLN5) was decreased in most of the data sets analyzed. We show that lactadherin accumulates with age in large cardiac blood vessels and when immobilized, triggers phosphorylation of several phosphosites of GSK3B, MAPK isoforms 1, 3, and 14, and MTOR kinases in aortic endothelial cells (ECs). In addition, immobilized lactadherin increased the expression of pro-inflammatory markers associated with an aging phenotype. These results extend our knowledge of the LV proteome remodeling induced by chronological and pathological aging in different species (mouse and human). The lactadherin-triggered changes in the proteome and phosphoproteome of ECs suggest a straight link between ECM component remodeling and the aging process of ECs.
2024-01-08 | PXD039548 | Pride
Project description:Impaired extracellular matrix (ECM) remodeling is a hallmark of many chronic inflammatory disorders that can lead to cellular dysfunction, aging, and disease progression. The ECM of the aged heart and its effects on cardiac cells during chronological and pathological aging are relatively poorly understood in several speciesacross species. Here, we used mass spectrometry-based proteomics to quantitatively characterize age-related remodeling of the left ventricle (LV) of mice and humans during chronological and pathological (Hutchinson-Gilford progeria syndrome (HGPS)) aging. Of the approximately 300 ECM proteins quantified, we identified 13 proteins that were increased, including lactadherin (MFGE8), collagen VI 6 (COL6A6), vitronectin (VTN) and immunoglobulin heavy constant mu (IGHM), whereas fibulin-5 (FBLN5) was decreased in most of the data sets analyzed. We show that lactadherin accumulates with age in large cardiac blood vessels and when immobilized, triggers phosphorylation of several phosphosites of GSK3B, MAPK isoforms 1, 3, and 14, and MTOR kinases in aortic endothelial cells (ECs). In addition, immobilized lactadherin increased the expression of pro-inflammatory markers associated with an aging phenotype. These results extend our knowledge of the LV proteome remodeling induced by chronological and pathological aging in different species (mouse and human). The lactadherin-triggered changes in the proteome and phosphoproteome of ECs suggest a straight link between ECM component remodeling and the aging process of ECs.
2024-01-08 | PXD040234 | Pride
Project description:The mechanistic target of rapamycin (mTOR) is a key regulator of pathological remodeling in the heart by activating ribosomal biogenesis and mRNA translation. Inhibition of mTOR in cardiomyocytes is protective, however, a detailed role of mTOR in translational regulation of specific mRNA networks in the diseased heart is largely unknown. A cardiomyocyte genome-wide sequencing approach was used to define mTOR-dependent post-transcriptional gene expression control at the level of mRNA translation. This approach identified the muscle specific protein Cullin-associated NEDD8-dissociated protein 2 (Cand2) as a translationally upregulated gene dependent on the activity of mTOR. Deletion of Cand2 protects the myocardium against pathological remodeling. Mechanistically, we found that Cand2 links mTOR- signaling to pathological cell growth by increasing Grk5 protein expression. Our data suggest that cell-type specific targeting of mTOR might have therapeutic value for adverse pathological cardiac remodeling.
2021-07-30 | GSE153364 | GEO
Project description:Cand2 links pathological mTORC1 signaling to adverse cardiac remodeling by regulating Grk5 expression
| PRJNA642148 | ENA
Project description:Comparative analysis of mouse cardiac left ventricle gene expression: voluntary wheel exercise and pregnancy-induced cardiac hypertrophy We performed microarray analysis on RNA from left ventricles of mice in non-pregnant diestrus cycle, mid-pregnancy (MP), late-pregnancy (LP), and immediate post-partum (0PP). These were compared to 7days (7EX) and 21 days (21EX) of voluntary wheel running exercise.
2012-03-08 | E-GEOD-36330 | biostudies-arrayexpress
Project description:This project is the comparison of protein profiles for pathological and physiological mouse cardiac hypertrophy
2018-07-30 | PXD010165 | Pride
Project description:Purpose: The physiological cardiac hypertrophy is an adaptive condition that does not associate with myocyte cell death while pathological hypertrophy is a maladaptive condition associated with myocyte cell death. Alpha-2 macroglobulin (α-2M) an acute phase protein induces cardiac hypertrophy via the ERK1,2 and PI3K/Akt signaling. This study is aimed at exploring the miRNome of α-2M induced hypertrophied cardiomyocytes and to understand the role of miRNAs in determination of pathological and physiological hypertrophy. Methods: Hypertrophy was induced in H9c2 cardiomyoblasts using alpha-2 macroglobulin. The induction of hypertrophy is confirmed by microscopy and gene expression studies. Subsequently, the total RNA was isolated and small RNA sequencing was executed in Illumina HiSeq 2000. Results: Analysis of small RNA reads revealed the differential expression of a large set of miRNAs during hypertrophy. Among the differentially expressed candidates, miR-99 family (miR-99a, miR-99b and miR-100) showed significant downregulation upon α-2M treatment while isoproterenol treatment (pathological hypertrophy) upregulated their expression. The binding site for Egr1 transcription factor was identified in the promoter region of miR-99 family, and interestingly all miRNAs with Egr1 binding site proven by ChIP-Seq were downregulated during physiological hypertrophy Conclusions: The results proved Egr-1 mediated regulation of miR-99 family determines the uniqueness of pathological and physiological hypertrophy. Upregulated miR-99 expression during pathological hypertrophy suggests that it can be a valuable diagnostic marker and potential therapeutic target for cardiac hypertrophy and heart failure. Small RNA profiles of control and hypertrophied cardiomyocyte H9c2 cells were generated by deep sequencing using Illumina HiSeq 2000
2015-11-01 | E-GEOD-73597 | biostudies-arrayexpress
Project description:Accute stretch and tachycardia are capable of inducing pathological excitation transcription coupling - an early invent before structural cardiac remodeling which transitions to heart failure. The sodium calcium exchanger is a key player in maintaining calcium homeostasis and is implicated in pathological signaling during heart failure. Neonatal rat ventricular cardiomyocytes (NRVCM) were subjected to mechanical stress and high freqency elecrical stimulation to study genes regulated during the early phase of trigger induced cardiac remodeling. Inhibition of the sodium calcium exchanger was used in an attempt to supress the early remodeling process and gain insight into the pathological signaling pathway.
2020-08-12 | GSE135172 | GEO