Ablation of biglycan attenuates cardiac hypertrophy and fibrosis after left ventricular pressure overload

Beetz, Nadine; Rommel, Carolin; Schnick, Tilman; Neumann, E; Lother, Achim; Monroy-Ordonez, Elsa Beatriz; Zeeb, Martin; Preißl, Sebastian; Gilsbach, Ralf; Melchior-Becker, Ariane; Rylski, Bartosz; Stoll, Monika; Schaefer, Liliana; Beyersdorf, Friedhelm; Stiller, Brigitte; Hein, Lutz

doi:10.1016/j.yjmcc.2016.10.011

Cited by 43 publications

(36 citation statements)

References 54 publications

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“…Biglycan and decorin are closely related ECM proteins belonging to the family of small leucine-rich proteoglycans (SLRP) yet having different properties with respect to cardiac remodelling and fibrosis. Although biglycan is an indispensable player in adaptive remodelling after MI [73], ablation of this protein in the setting of left ventricular pressure overload attenuates cardiac hypertrophy [74]. Extracellular decorin, however, has an antifibrotic effect and inhibits the action of TGFβ on human cardiac fibroblasts.…”

Section: Cardiac Fibrosismentioning

confidence: 99%

From Inflammation to Fibrosis—Molecular and Cellular Mechanisms of Myocardial Tissue Remodelling and Perspectives on Differential Treatment Opportunities

Suthahar

Meijers

Silljé

et al. 2017

Curr Heart Fail Rep

247

159

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Purpose of ReviewIn this review, we highlight the most important cellular and molecular mechanisms that contribute to cardiac inflammation and fibrosis. We also discuss the interplay between inflammation and fibrosis in various precursors of heart failure (HF) and how such mechanisms can contribute to myocardial tissue remodelling and development of HF.Recent FindingsRecently, many research articles attempt to elucidate different aspects of the interplay between inflammation and fibrosis. Cardiac inflammation and fibrosis are major pathophysiological mechanisms operating in the failing heart, regardless of HF aetiology. Currently, novel therapeutic options are available or are being developed to treat HF and these are discussed in this review.SummaryA progressive disease needs an aggressive management; however, existing therapies against HF are insufficient. There is a dynamic interplay between inflammation and fibrosis in various precursors of HF such as myocardial infarction (MI), myocarditis and hypertension, and also in HF itself. There is an urgent need to identify novel therapeutic targets and develop advanced therapeutic strategies to combat the syndrome of HF. Understanding and describing the elements of the inflammatory and fibrotic pathways are essential, and specific drugs that target these pathways need to be evaluated.

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Section: Cardiac Fibrosismentioning

confidence: 99%

From Inflammation to Fibrosis—Molecular and Cellular Mechanisms of Myocardial Tissue Remodelling and Perspectives on Differential Treatment Opportunities

Suthahar

Meijers

Silljé

et al. 2017

Curr Heart Fail Rep

247

159

View full text Add to dashboard Cite

show abstract

“…A pro-fibrotic proteoglycan that co-localizes with and stabilizes collagen; necessary in wound healing following MI, but is detrimental following pressure overload through increased cardiac fibrosis [39,40].…”

Section: Expression In Fibrotic Heart Disease Role In Fibrotic Heart mentioning

confidence: 99%

“…Biglycan is expressed in the healthy heart and its expression is increased following MI or pressure overload [38]. Biglycan has been found to co-localize with collagen fibers in the infarct scar [40], and its expression is increased in activated fibroblasts, but not in other cardiac cells following pressure overload [39]. In addition, biglycan knockout mice demonstrate reduced hypertrophy and cardiac fibrosis following pressure overload [39].…”

Section: Small Leucine Rich Proteoglycansmentioning

confidence: 99%

The Non-Fibrillar Side of Fibrosis: Contribution of the Basement Membrane, Proteoglycans, and Glycoproteins to Myocardial Fibrosis

Chute

Aujla

Jana

et al. 2019

JCDD

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The extracellular matrix (ECM) provides structural support and a microenvironmentfor soluble extracellular molecules. ECM is comprised of numerous proteins which can be broadly classified as fibrillar (collagen types I and III) and non-fibrillar (basement membrane, proteoglycans, and glycoproteins). The basement membrane provides an interface between the cardiomyocytes and the fibrillar ECM, while proteoglycans sequester soluble growth factors and cytokines. Myocardial fibrosis was originally only linked to accumulation of fibrillar collagens, but is now recognized as the expansion of the ECM including the non-fibrillar ECM proteins. Myocardial fibrosis can be reparative to replace the lost myocardium (e.g., ischemic injury or myocardial infarction), or can be reactive resulting from pathological activity of fibroblasts (e.g., dilated or hypertrophic cardiomyopathy). Contribution of fibrillar collagens to fibrosis is well studied, but the role of the non-fibrillar ECM proteins has remained less explored. In this article, we provide an overview of the contribution of the non-fibrillar components of the extracellular space of the heart to highlight the potential significance of these molecules in fibrosis, with direct evidence for some, although not all of these molecules in their direct contribution to fibrosis.

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“…Thus, the role of HMGB1 as TLR4 ligand and upstream inducer of NF-κB and NLRP3 may shape a key pathogenic axis in diabetic cardiomyopathy, suggesting their potential as novel anti-inflammatory approaches. In this context, other ligands for TLR (TLR2 and TLR4) such as biglycan could also play a key role in amplifying fibrotic responses after cardiac injury (Beetz et al, 2016). …”

Section: Il-1β Inhibition and Diabetic Cardiomyopathymentioning

confidence: 99%

IL-1β Inhibition in Cardiovascular Complications Associated to Diabetes Mellitus

et al. 2017

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Diabetes mellitus (DM) is a chronic disease that affects nowadays millions of people worldwide. In adults, type 2 diabetes mellitus (T2DM) accounts for the majority of all diagnosed cases of diabetes. The course of the T2DM is characterized by insulin resistance and a progressive loss of β-cell mass. DM is associated with a number of related complications, among which cardiovascular complications and atherosclerosis are the main cause of morbidity and mortality in patients suffering from the disease. DM is acknowledged as a low-grade chronic inflammatory state characterized by the over-secretion of pro-inflammatory cytokines, including interleukin (IL)-1β, which reinforce inflammatory signals thus contributing to the development of complications. In this context, the pharmacological approaches to treat diabetes should not only correct hyperglycaemia, but also attenuate inflammation and prevent the development of metabolic and cardiovascular complications. Over the last years, novel biological drugs have been developed to antagonize the pathophysiological actions of IL-1β. The drugs currently used in clinical practice are anakinra, a recombinant form of the naturally occurring IL-1 receptor antagonist, the soluble decoy receptor rilonacept and the monoclonal antibodies canakinumab and gevokizumab. This review will summarize the main experimental and clinical findings obtained with pharmacological IL-1β inhibitors in the context of the cardiovascular complications of DM, and discuss the perspectives of IL-1β inhibitors as novel therapeutic tools for treating these patients.

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Ablation of biglycan attenuates cardiac hypertrophy and fibrosis after left ventricular pressure overload

Cited by 43 publications

References 54 publications

From Inflammation to Fibrosis—Molecular and Cellular Mechanisms of Myocardial Tissue Remodelling and Perspectives on Differential Treatment Opportunities

From Inflammation to Fibrosis—Molecular and Cellular Mechanisms of Myocardial Tissue Remodelling and Perspectives on Differential Treatment Opportunities

The Non-Fibrillar Side of Fibrosis: Contribution of the Basement Membrane, Proteoglycans, and Glycoproteins to Myocardial Fibrosis

IL-1β Inhibition in Cardiovascular Complications Associated to Diabetes Mellitus

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