Circulating Relaxin-1 Level Is a Surrogate Marker of Myocardial Fibrosis in HFrEF

Simon, Judit; Németh, Endre; Nemes, A.; Husveth-Toth, M; Radovits, Tamás; Földes, Gábor; Kiss, Loretta; Bagyura, Zsolt; Skopál, Judit; Merkely, Béla; Gara, Edit

doi:10.3389/fphys.2019.00690

Cited by 13 publications

(10 citation statements)

References 55 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Well-characterized, de-identified human myocardial tissue samples were obtained from the Transplantation Biobank of the Heart and Vascular Center at Semmelweis University, Budapest, Hungary [31,32]. The procedure of sample procurement was reviewed and approved by the institutional and national ethics committee (ethical permission numbers: ETT TUKEB 7891/2012/EKU (119/ PI/12.)…”

Section: Methodsmentioning

confidence: 99%

Characterization of left ventricular myocardial sodium-glucose cotransporter 1 expression in patients with end-stage heart failure

Sayour

Oláh

Ruppert

et al. 2020

Cardiovasc Diabetol

View full text Add to dashboard Cite

Background Whereas selective sodium-glucose cotransporter 2 (SGLT2) inhibitors consistently showed cardiovascular protective effects in large outcome trials independent of the presence of type 2 diabetes mellitus (T2DM), the cardiovascular effects of dual SGLT1/2 inhibitors remain to be elucidated. Despite its clinical relevance, data are scarce regarding left ventricular (LV) SGLT1 expression in distinct heart failure (HF) pathologies. We aimed to characterize LV SGLT1 expression in human patients with end-stage HF, in context of the other two major glucose transporters: GLUT1 and GLUT4. Methods Control LV samples (Control, n = 9) were harvested from patients with preserved LV systolic function who went through mitral valve replacement. LV samples from HF patients undergoing heart transplantation (n = 71) were obtained according to the following etiological subgroups: hypertrophic cardiomyopathy (HCM, n = 7); idiopathic dilated cardiomyopathy (DCM, n = 12); ischemic heart disease without T2DM (IHD, n = 14), IHD with T2DM (IHD + T2DM, n = 11); and HF patients with cardiac resynchronization therapy (DCM:CRT, n = 9, IHD:CRT, n = 9 and IHD-T2DM:CRT, n = 9). We measured LV SGLT1, GLUT1 and GLUT4 gene expressions with qRT-PCR. The protein expression of SGLT1, and activating phosphorylation of AMP-activated protein kinase (AMPKα) and extracellular signal-regulated kinase 1/2 (ERK1/2) were quantified by western blotting. Immunohistochemical staining of SGLT1 was performed. Results Compared with controls, LV SGLT1 mRNA and protein expressions were significantly and comparably upregulated in HF patients with DCM, IHD and IHD + T2DM (all P < 0.05), but not in HCM. LV SGLT1 mRNA and protein expressions positively correlated with LVEDD and negatively correlated with EF (all P < 0.01). Whereas AMPKα phosphorylation was positively associated with SGLT1 protein expression, ERK1/2 phosphorylation showed a negative correlation (both P < 0.01). Immunohistochemical staining revealed that SGLT1 expression was predominantly confined to cardiomyocytes, and not fibrotic tissue. Overall, CRT was associated with reduction of LV SGLT1 expression, especially in patients with DCM. Conclusions Myocardial LV SGLT1 is upregulated in patients with HF (except in those with HCM), correlates significantly with parameters of cardiac remodeling (LVEDD) and systolic function (EF), and is downregulated in DCM patients with CRT. The possible role of SGLT1 in LV remodeling needs to be elucidated.

show abstract

Section: Methodsmentioning

confidence: 99%

Characterization of left ventricular myocardial sodium-glucose cotransporter 1 expression in patients with end-stage heart failure

Sayour

Oláh

Ruppert

et al. 2020

Cardiovasc Diabetol

View full text Add to dashboard Cite

show abstract

“…Well-characterized de-identified human myocardial tissue samples were obtained from the Transplantation Biobank of the Heart and Vascular Center at Semmelweis University, Budapest, Hungary [ 34 , 35 ]. Following institutional and national ethical committee approval (ethical permission numbers: ETT TUKEB 7891/2012/EKU (119/PI/12.)…”

Section: Methodsmentioning

confidence: 99%

Cardiomyocyte Oga haploinsufficiency increases O-GlcNAcylation but hastens ventricular dysfunction following myocardial infarction

et al. 2020

View full text Add to dashboard Cite

Rationale The beta-O-linkage of N-acetylglucosamine (i.e., O-GlcNAc) to proteins is a pro-adaptive response to cellular insults. To this end, increased protein O-GlcNAcylation improves short-term survival of cardiomyocytes subjected to acute injury. This observation has been repeated by multiple groups and in multiple models; however, whether increased protein O-GlcNAcylation plays a beneficial role in more chronic settings remains an open question. Objective Here, we queried whether increasing levels of cardiac protein O-GlcNAcylation would be beneficial during infarct-induced heart failure. Methods and results To achieve increased protein O-GlcNAcylation, we targeted Oga, the gene responsible for removing O-GlcNAc from proteins. Here, we generated mice with cardiomyocyte-restricted, tamoxifen-inducible haploinsufficient Oga gene. In the absence of infarction, we observed a slight reduction in ejection fraction in Oga deficient mice. Overall, Oga reduction had no major impact on ventricular function. In additional cohorts, mice of both sexes and both genotypes were subjected to infarct-induced heart failure and followed for up to four weeks, during which time cardiac function was assessed via echocardiography. Contrary to our prediction, the Oga deficient mice exhibited exacerbated—not improved—cardiac function at one week following infarction. When the observation was extended to 4 wk post-MI, this acute exacerbation was lost. Conclusions The present findings, coupled with our previous work, suggest that altering the ability of cardiomyocytes to either add or remove O-GlcNAc modifications to proteins exacerbates early infarct-induced heart failure. We speculate that more nuanced approaches to regulating O-GlcNAcylation are needed to understand its role—and, in particular, the possibility of cycling, in the pathophysiology of the failing heart.

show abstract

“…RLN, a polypeptide hormone, is secreted by cardiac cells [114]. In a cross-sectional study, the average circulating RLN1 levels in the HFrEF patient population were markedly higher than those in healthy control subjects (702 ± 283 pg/mL vs. 44 ± 27 pg/mL), with elevated RLN1 levels accompanied by a decrease in heart fibrosis [115]. This finding promotes the study of RLN1 as a potential anti-fibrosis target.…”

Section: Other Moleculesmentioning

confidence: 88%

Roles of Biomarkers in Myocardial Fibrosis

et al. 2020

View full text Add to dashboard Cite

Myocardial fibrosis is observed in various cardiovascular diseases and plays a key role in the impairment of cardiac function. Endomyocardial biopsy, as the gold standard for the diagnosis of myocardial fibrosis, has limitations in terms of clinical application. Therefore, biomarkers have been recommended for noninvasive assessment of myocardial fibrosis. This review discusses the role of biomarkers in myocardial fibrosis from the perspective of collagen.

show abstract

Circulating Relaxin-1 Level Is a Surrogate Marker of Myocardial Fibrosis in HFrEF

Cited by 13 publications

References 55 publications

Characterization of left ventricular myocardial sodium-glucose cotransporter 1 expression in patients with end-stage heart failure

Characterization of left ventricular myocardial sodium-glucose cotransporter 1 expression in patients with end-stage heart failure

Cardiomyocyte Oga haploinsufficiency increases O-GlcNAcylation but hastens ventricular dysfunction following myocardial infarction

Roles of Biomarkers in Myocardial Fibrosis

Contact Info

Product

Resources

About