Atrial expression of the CCN1 and CCN2 proteins in chronic heart failure

Bonda, Tomasz A.; Kamiński, Karol; Dziemidowicz, Magdalena; Литвинович, С. Н.; Kożuch, Marcin; Hirnle, Tomasz; Dmitruk, Iwona; Chyczewski, L; Winnicka, Maria M.

doi:10.5603/fhc.2012.0014

Cited by 12 publications

(11 citation statements)

References 21 publications

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“…It has also been reported that CCN1 expression can be induced by angiotensin II and phenylephrine or ischemic stress in cardiomyocytes. Expression of CCN1 is nearly absent in the non-failing heart, whereas increased CCN1 levels have been detected in the atrial myocardium in an animal model of chronic heart failure [21]. Interestingly, Yoshida et al found that CCN1 increased the survival of myocytes by activating the integrin β1-Akt pathway under conditions of oxidative stress, whereas knockdown of CCN1 decreased the number of surviving cells under these conditions, indicating that CCN1 is a protector of ischemic myocytes [22].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of Serum Cysteine-Rich Protein 61 in Patients with Acute Heart Failure

Zhao

Zhang

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cyr61-cysteine-rich protein 61 (CCN1/CYR61) is a multifunctional matricellular protein involved in the regulation of fibrogenesis. Animal experiments have demonstrated that CCN1 can inhibit cardiac fibrosis in cardiac hypertrophy. However, no study has been conducted to assess the relation between serum CCN1 and prognosis of acute heart failure (AHF). Methods: We measured the serum CCN1 levels of 183 patients with AHF, and the patients were followed up for 6 months. The associations between CCN1 levels and some clinical covariates, especially left ventricular ejection fraction (LVEF), estimated glomerular filtration rate (eGFR), atrial fibrillation and age, were estimated. The AHF patients were followed up for 6 months. The endpoint was all-cause mortality. Kaplan-Meier curve analysis and multivariable Cox proportional hazards analysis were employed to evaluate the prognostic ability of CCN1. We used calibration, discrimination and reclassification to assess the mortality risk prediction of adding CCN1. Results: Serum CCN1 concentrations in AHF patients were significantly increased compared with those in individuals without AHF (237 pg/ml vs. 124.8 pg/ml, p< 0.001). CCN1 level was associated with the level of NT-proBNP (r=0.349, p< 0.001) and was not affected by LVEF, eGFR, age or atrial fibrillation in AHF patients. Importantly, Kaplan-Meier curve analysis illustrated that the AHF patients with serum CCN1 level > 260 pg/ ml had a lower survival rate (p< 0.001). Multivariate Cox hazard analysis suggests that CCN1 functions as an independent predictor of mortality for AHF patients (LgCCN1, hazard ratio 5.825, 95% confidence interval: 1.828-18.566, p=0.003). In addition, the inclusion of CCN1 in the model with NT-proBNP significantly improved the C-statistic for predicting death (0.758, p< 0.001). The integrated discrimination index was 0.019 (p< 0.001), and the net reclassification index increased significantly after addition of CCN1 (23.9%, p=0.0179). Conclusions: CCN1 is strongly predictive of 6-month mortality in patients with AHF, suggesting serum CCN1 as a promising candidate prognostic biomarker for AHF patients.

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Section: Discussionmentioning

confidence: 99%

Prognostic Significance of Serum Cysteine-Rich Protein 61 in Patients with Acute Heart Failure

Zhao

Zhang

Liu

et al. 2018

Cell Physiol Biochem

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“…Ccn1 (gene name in Fig. 3 is Cyr61) is a matricellular protein whose expression has been associated with heart failure 47 . Mice deficient for Col15a1 (type XV collagen) also have heart defects 48, 49 .…”

Section: Resultsmentioning

confidence: 99%

Heart Failure and MEF2 Transcriptome Dynamics in Response to β-Blockers

Tobin

Hashemi

Dadson

et al. 2017

Sci Rep

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Myocyte Enhancer Factor 2 (MEF2) mediates cardiac remodelling in heart failure (HF) and is also a target of β-adrenergic signalling, a front-line treatment for HF. We identified global gene transcription networks involved in HF with and without β-blocker treatment. Experimental HF by transverse aortic constriction (TAC) in a MEF2 “sensor” mouse model (6 weeks) was followed by four weeks of β-blockade with Atenolol (AT) or Solvent (Sol) treatment. Transcriptome analysis (RNA-seq) from left ventricular RNA samples and MEF2A depleted cardiomyocytes was performed. AT treatment resulted in an overall improvement in cardiac function of TAC mice and repression of MEF2 activity. RNA-seq identified 65 differentially expressed genes (DEGs) due to TAC treatment with enriched GO clusters including the inflammatory system, cell migration and apoptosis. These genes were mapped against DEGs in cardiomyocytes in which MEF2A expression was suppressed. Of the 65 TAC mediated DEGs, AT reversed the expression of 28 mRNAs. Rarres2 was identified as a novel MEF2 target gene that is upregulated with TAC in vivo and isoproterenol treatment in vitro which may have implications in cardiomyocyte apoptosis and hypertrophy. These studies identify a cohort of genes with vast potential for disease diagnosis and therapeutic intervention in heart failure.

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“…The stimulatory effects of S1P on an increase in the expression of CCN1 and CCN2 are substantially faster than those on the expression of COX2, indicating that CCN proteins are the upstream effectors of COX2 upregulation. Previous studies have shown that CCN1 and CCN2 are simultaneously upregulated in response to various stimulants, which, in turn, modulate multiple functions in certain mammalian cells [44,45,46]. Considering the critical roles of CCN1 and CCN2 in the regulation of follicular development and ovulation, we sought to investigate the involvement of CCN proteins in the S1P-induced upregulation of COX2.…”

Section: Discussionmentioning

confidence: 99%

CCN2 Mediates S1P-Induced Upregulation of COX2 Expression in Human Granulosa-Lutein Cells

Chang

et al. 2019

Cells

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CCN1 and CCN2 are members of the CCN family and play essential roles in the regulation of multiple female reproductive functions, including ovulation. Cyclooxygenase-2 (COX2) is a critical mediator of ovulation and can be induced by sphingosine-1-phosphate (S1P) through the S1P1/3-mediated Yes-associated protein (YAP) signaling. However, it is unclear whether CCN1 or CCN2 can mediate S1P-induced upregulation of COX2 expression and increase in prostaglandin E2 (PGE2) production in human granulosa-lutein (hGL) cells. In the present study, we investigated the effects of S1P on the expressions of CCN1 and CCN2 in hGL cells. Additionally, we used a dual inhibition approach (siRNA-mediated silencing and small molecular inhibitors) to investigate the molecular mechanisms of S1P effects. Our results showed that S1P treatment significantly upregulated the expression of CCN1 and CCN2 in a concentration-dependent manner in hGL cells. Additionally, inhibition or silencing of S1P1, but not S1P3, completely abolished the S1P-induced upregulation of CCN2 expression. Furthermore, we demonstrated that S1P-induced nuclear translocation of YAP and inhibition or silencing of YAP completely abolished the S1P-induced upregulation of CCN1 and CCN2 expression. Notably, silencing of CCN2, but not CCN1, completely reversed the S1P-induced upregulation of COX2 expression and the increase in PGE2 production. Thus, CCN2 mediates the S1P-induced upregulation of COX2 expression through the S1P1-mediated signaling pathway in hGL cells. Our findings expand our understanding of the molecular mechanism underlying the S1P-mediated cellular activities in the human ovary.

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Atrial expression of the CCN1 and CCN2 proteins in chronic heart failure

Cited by 12 publications

References 21 publications

Prognostic Significance of Serum Cysteine-Rich Protein 61 in Patients with Acute Heart Failure

Prognostic Significance of Serum Cysteine-Rich Protein 61 in Patients with Acute Heart Failure

Heart Failure and MEF2 Transcriptome Dynamics in Response to β-Blockers

CCN2 Mediates S1P-Induced Upregulation of COX2 Expression in Human Granulosa-Lutein Cells

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