Chronic Benzene Exposure Aggravates Pressure Overload-Induced Cardiac Dysfunction
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ABSTRACT:
PROVIDER: PRJNA792555 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17334641_1.fastq.gz | Fastqsanger.gz | |||
| SRR17334641_2.fastq.gz | Fastqsanger.gz | |||
| SRR17334642_1.fastq.gz | Fastqsanger.gz | |||
| SRR17334642_2.fastq.gz | Fastqsanger.gz | |||
| SRR17334643_1.fastq.gz | Fastqsanger.gz |
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Project description:Benzene is a ubiquitous environmental pollutant abundant in household products, petrochemicals and cigarette smoke. Benzene is a well-known carcinogen in humans and experimental animals; however, little is known about the cardiovascular toxicity of benzene. Recent population-based studies indicate that benzene exposure is associated with an increased risk for heart failure. Nonetheless, it is unclear whether benzene exposure is sufficient to induce and/or exacerbate heart failure. We examined the effects of benzene (50 ppm, 6 h/day, 5 days/week, 6 weeks) or HEPA-filtered air exposure on transverse aortic constriction (TAC)-induced pressure overload in male C57BL/6J mice. Our data show that benzene exposure had no effect on cardiac function in the Sham group; however, it significantly compromised cardiac function as depicted by a significant decrease in fractional shortening and ejection fraction, as compared with TAC/Air-exposed mice. RNA-seq analysis of the cardiac tissue from the TAC/benzene-exposed mice showed a significant increase in several genes associated with adhesion molecules, cell-cell adhesion, inflammation, and stress response. In particular, neutrophils were implicated in our unbiased analyzes. Indeed, immunofluorescence studies showed that TAC/benzene exposure promotes infiltration of CD11b+/S100A8+/myeloperoxidase+-positive neutrophils in the hearts by 3-fold. In vitro, the benzene metabolites, hydroquinone and catechol, induced the expression of P-selectin in cardiac microvascular endothelial cells by 5-fold and increased the adhesion of neutrophils to these endothelial cells by 1.5-2.0-fold. Benzene metabolite-induced adhesion of neutrophils to the endothelial cells was attenuated by anti-P-selectin antibody. Together, these data suggest that benzene exacerbates heart failure by promoting endothelial activation and neutrophil recruitment.
2021-12-30 | GSE192643 | GEO
Project description:Targeting cardiac remodeling is regarded as a key therapeutic strategy for heart failure. Kielin/chordin-like protein (KCP) is a secretory protein with 18 cysteine-rich domains and associated with kidney and liver fibrosis. However, the relationship between KCP and cardiac remodeling remains unclear. Here, we aimed to investigate the role of KCP in cardiac remodeling induced by pressure overload and explore its potential mechanisms. Left ventricular (LV) KCP expression was measured with real-time quantitative PCR, western blotting, and immunofluorescence staining in pressure overload-induced cardiac remodeling in mice. Cardiac function and remodeling were evaluated in wide-type (WT) mice and KCP knockout (KO) mice by echocardiography, which were further confirmed by histological analysis with hematoxylin and eosin and Masson staining. RNA sequence was performed with LV tissue from WT and KO mice to identify differentially expressed genes and related signaling pathways. Primary cardiac fibroblasts (CFs) were used to validate the regulatory role and potential mechanisms of KCP during fibrosis. KCP was down-regulated in the progression of cardiac remodeling induced by pressure overload, and was mainly expressed in fibroblasts. KCP deficiency significantly aggravated pressure overload-induced cardiac dysfunction and remodeling. RNA sequence revealed that the role of KCP deficiency in cardiac remodeling was associated with cell division, cell cycle, and P53 signaling pathway, while cyclin B1 (CCNB1) was the most significantly up-regulated gene. Further investigation in vivo and in vitro suggested that KCP deficiency promoted the proliferation of CFs via P53/P21/CCNB1 pathway. Taken together, these results suggested that KCP deficiency aggravates cardiac dysfunction and remodeling induced by pressure overload via P53/P21/CCNB1 signaling in mice.
2025-06-01 | GSE283181 | GEO
Project description:Lionheart LincRNA Alleviates Cardiac Systolic Dysfunction under Pressure Overload
| PRJNA644194 | ENA
Project description:Benzene is a ubiquitous environmental pollutant abundant in household products, petrochemicals, and cigarette smoke. Benzene is a well-known carcinogen in humans and experimental animals; however, little is known about the cardiovascular toxicity of benzene. Recent population-based studies indicate that benzene exposure is associated with an increased risk for heart failure. Nonetheless, it is unclear whether benzene exposure is sufficient to induce and/or exacerbate heart failure. We examined the effects of benzene (50 ppm, 6 h/day, 5 days/week, and 6 weeks) or high-efficiency particulate absorbing-filtered air exposure on transverse aortic constriction (TAC)-induced pressure overload in male C57BL/6J mice. Our data show that benzene exposure had no effect on cardiac function in the Sham group; however, it significantly compromised cardiac function as depicted by a significant decrease in fractional shortening and ejection fraction, as compared with TAC/Air-exposed mice. RNA-seq analysis of the cardiac tissue from the TAC/benzene-exposed mice showed a significant increase in several genes associated with adhesion molecules, cell-cell adhesion, inflammation, and stress response. In particular, neutrophils were implicated in our unbiased analyses. Indeed, immunofluorescence studies showed that TAC/benzene exposure promotes infiltration of CD11b+/S100A8+/myeloperoxidase+-positive neutrophils in the hearts by 3-fold. In vitro, the benzene metabolites, hydroquinone, and catechol, induced the expression of P-selectin in cardiac microvascular endothelial cells by 5-fold and increased the adhesion of neutrophils to these endothelial cells by 1.5- to 2.0-fold. Benzene metabolite-induced adhesion of neutrophils to the endothelial cells was attenuated by anti-P-selectin antibody. Together, these data suggest that benzene exacerbates heart failure by promoting endothelial activation and neutrophil recruitment.
| S-EPMC8714365 | biostudies-literature
Project description:Failure of molecular chaperones to direct the correct folding of newly synthesized proteins leads to the accumulation of misfolded proteins in cells. HSPA4 is a member of the heat shock protein 110 family (HSP110) that acts as a nucleotide exchange factor of HSP70 chaperones. We found that the expression of HSPA4 is upregulated in murine hearts subjected to pressure overload and in failing human hearts. To investigate the cardiac function of HSPA4, Hspa4 knockout (KO) mice were generated and exhibited cardiac hypertrophy and fibrosis. Hspa4 KO hearts were characterized by a significant increase in heart weight/body weight ratio, elevated expression of hypertrophic and fibrotic gene markers, and concentric hypertrophy with preserved contractile functions. Cardiac hypertrophy in Hspa4 KO hearts was associated with enhanced activation of gp130-STAT3, CaMKII, and calcineurin-NFAT signaling. Further analyses revealed a significant increase in cross sectional area of cardiomyocytes, and in expression levels of hypertrophic markers in cultured neonatal Hspa4 KO cardiomyocytes suggesting that the hypertrophy of mutant mice was a result of primary defects in cardiomyocytes. Gene expression profile in hearts of 3.5-week-old mice revealed a differentially expressed gene sets related to ion channels and stress response. Taken together, these results reveal that HSPA4 is implicated in protection against pressure overload-induced heart failure. Total RNA was extracted from heart ventricles of 3.5-week-old Hspa4+/+ and Hspa4-/- males (n = 3 mice for each genotype).
2012-10-10 | E-GEOD-32885 | biostudies-arrayexpress
Project description:Aim was to investigate the effect of cardiomyocyte-specific expression of the human Relaxin Family Peptide Receptor 1 (RXFP1) in a mouse model of pressure-overload induced cardiac dysfunction (TAC). Mice overexpressing the hRXFP1 receptor (or non-transgenic controls) underwent TAC (or Sham) surgery and were followed up for 8 weeks. Heart was removed and RNA isolated from left ventricle to perform bulk RNAseq.
2024-05-23 | GSE252607 | GEO
Project description:Background Chronic sustained pressure overload induces cardiac remodeling, which often leads to heart failure. Cardiac macrophages (cMacs) are heterogeneous cell populations, and their elimination has been shown to exacerbate pressure overload-induced heart failure. CD163, a macrophage-specific scavenger receptor expressed in a subset of cMacs, has been linked to cardiovascular events through its serum soluble form. This study aimed to elucidate the functional role of the CD163+ cMacs subset in pressure overload-induced heart failure. Methods Transverse aortic constriction (TAC) was performed on wild-type and CD163-deficient (Cd163-/-) mice to investigate the role of CD163 in pressure overload-induced cardiac remodeling and heart failure. Echocardiography was used to assess heart structure and function. Transcriptomic analysis and transmission electron microscopy were employed to observe mitochondrial structure in cardiomyocytes. Flow cytometry was used to quantify cMacs and cytokine-expressing cMacs in the heart. Additionally, serum samples from hypertensive patients with and without heart failure were analyzed to explore the relationship between CD163 and heart failure. Results TAC-induced left ventricular systolic dysfunction, including reduced ejection fraction and fractional shortening, was significantly aggravated in Cd163-/- mice post-surgery. Genes differentially expressed due to CD163 deficiency were enriched in pathways related to mitochondrial bioenergetics and homeostasis. Transmission electron microscopy revealed an increase in dysfunctional mitochondria in cardiomyocytes of Cd163-/- mice post-TAC. Additionally, decreased serum interleukin (IL)-10 levels and reduced IL-10 expression in cMacs were observed in Cd163-/- mice post-TAC. IL-10 supplementation significantly reversed TAC-induced reductions in left ventricular systolic function and improved mitochondrial bioenergetics and homeostasis in Cd163-/- mice. Conclusions The protective functions of CD163 in cMacs are associated with IL-10 expression during pressure overload-induced heart failure.
2025-05-08 | GSE277624 | GEO
Project description:Background: In complex congenital heart disease patients such as those with tetralogy of Fallot, the right ventricle (RV) is subject to pressure overload, leading to RV hypertrophy and eventually RV failure. The mechanisms that promote the transition from stable RV hypertrophy to RV failure are unknown. We evaluated the role of mitochondrial bioenergetics in the development of RV failure. Methods: We created a murine model of RV pressure overload by pulmonary artery banding and compared with sham-operated controls. Gene expression by RNA-sequencing, oxidative stress, mitochondrial respiration, dynamics, and structure were assessed in pressure overload-induced RV failure. Results: RV failure was characterized by decreased expression of electron transport chain genes and mitochondrial antioxidant genes (aldehyde dehydrogenase 2 and superoxide dismutase 2) and increased expression of oxidant stress markers (heme oxygenase, 4-hydroxynonenal). The activities of all electron transport chain complexes decreased with RV hypertrophy and further with RV failure (oxidative phosphorylation: sham 552.3±43.07 vs. RV hypertrophy 334.3±30.65 vs. RV failure 165.4±36.72 pmol/(sec*ml), p<0.0001). Mitochondrial fission protein DRP1 did not change, while MFF decreased and fusion protein OPA1 decreased. In contrast, transcription of electron transport chain genes increased in the left ventricle of RV failure. Conclusion: Pressure overload-induced RV failure is characterized by decreased transcription and activity of electron transport chain complexes and increased oxidative stress which are associated with decreased energy generation. An improved understanding of the complex processes of energy generation could aid in developing novel therapies to mitigate mitochondrial dysfunction and delay the onset of RV failure.
2021-03-18 | GSE152413 | GEO
Project description:Kielin/chordin-like protein deficiency aggravates pressure overload-induced cardiac dysfunction and remodeling via P53/P21/CCNB1 signaling in mice
| PRJNA1192285 | ENA
Project description:Myocardial deletion of klf4 sensitizes mouse to pressure overload. In order to gain a better understanding of molecular mechanisms of such alterations, we profiled gene expression before and after 3-day of pressure overload (induced by transverse aortic constriction -TAC) in the hearts from MHC-cre (Cre) control and MHC-cre-klf4-deficient (KO) mice. 10wk old male mice was subjected to transverse aortic constriction (TAC) to induce pressure overload or sham operation as control group. After 3 days, heart was removed and total RNA was extracted from apex and subjected for array analysis. Four animals in each group.
2015-07-01 | E-GEOD-61177 | biostudies-arrayexpress