Fibrosis in endstage human heart failure: Severe changes in collagen metabolism and MMP/TIMP profiles

Polyakova, V. O.; Loeffler, Ivo; Hein, Stefan; Miyagawa, Shigeru; Piotrowska, Izabela; Dammer, Sebastian; Risteli, Juha; Schaper, Jutta; Kostin, Sawa

doi:10.1016/j.ijcard.2010.04.053

Cited by 131 publications

(147 citation statements)

References 48 publications

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“…However, adequate concentrations of vitamin D can suppress the inflammatory response through inhibition of the prostaglandin and cyclooxygenase, overstimulation of anti‐inflammatory cytokines, reduction of cytokines induced by expression of adhesion molecules, reduction of extracellular matrix metalloproteinases, and inhibition of the release of the pro‐inflammatory factor NF‐kappa beta, which is associated with endothelial dysfunction 24. Calcitriol stimulates the tissue inhibitors of metalloproteinases, preventing excessive degradation of the extracellular matrix through the MMPs, particularly MMP‐2 and MMP‐9, which consequently lead to ventricular progressive remodelling, dilatation, and HF 25. Another inflammatory mechanism through which vitamin D deficiency acts, by increasing the risk of HF, is through the decrease of Treg cells and the increase of Th17,26 as well as through their polymorphisms VDR‐type BSMI receiver, which were related to left ventricular hypertrophy 27…”

Section: Discussionmentioning

confidence: 99%

Association between vitamin D deficiency and heart failure risk in the elderly

Porto

Silva

Luz³

et al. 2017

ESC Heart Failure

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AimsThe aim of this study was to evaluate the association between vitamin D deficiency and risk of heart failure in elderly patients of cardiology outpatient clinics.Methods and resultsA cross‐sectional study with an analytical approach was employed. Clinical data were collected from the elderly from August 2015 to February 2016. The dependent variable was the risk of heart failure; the independent variable was vitamin D deficiency; and intervening factors were age, gender, education, ethnicity, hypertension, diabetes mellitus, hypothyroidism, renal failure, dementia, stroke, dyslipidaemia, depression, smoking, alcoholism, obesity, andropause, and cardiac arrhythmia. To analyse the association between vitamin D deficiency and risk of heart failure, we used the bivariate logistic analysis, followed by analysis through the multivariate logistic regression model. Of the 137 elderly, the study found the following: women (75.9%); overweight (48.2%); obese (30.6%); increase in the index waist/hip (88.3%); dyslipidaemia (94.2%) and hypertension (91.2%); coronary artery disease (35.0%); and 27.7% with cardiac arrhythmia or left ventricular hypertrophy. Sixty‐five per cent of the elderly were deficient in vitamin D. The risk of heart failure was significantly associated with vitamin D deficiency [odds ratio (OR): 12.19; 95% confidence interval (CI) = 4.23–35.16; P = 0.000], male gender (OR: 15.32; 95% CI = 3.39–69.20, P = 0.000), obesity (OR: 4.17; 95% CI = 1.36–12.81; P = 0.012), and cardiac arrhythmia (OR: 3.69; 95% CI = 1.23–11.11; P = 0.020).ConclusionsThere was a high prevalence of vitamin D deficiency in the elderly, and the evidence shows a strong association between vitamin D deficiency and increased risk of heart failure in this population.

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Section: Discussionmentioning

confidence: 99%

Association between vitamin D deficiency and heart failure risk in the elderly

Porto

Silva

Luz³

et al. 2017

ESC Heart Failure

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“…Patients suffering from final stage heart failure (ejection fraction ≤23%) due to DCM (18 patients), ICM (7 patients) and myocarditis (9 patients) were examined [18]. Samples from donor hearts with normal left ventricular function which could not be used for transplantation served as controls.…”

Section: Tissue Samplesmentioning

confidence: 99%

Oncostatin M Induces FGF23 Expression in Cardiomyocytes

Richter¹,

Polyakova²,

Gajawada³

2012

J Clin Exp Cardiolog

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Background: It is well-known that elevated levels of Fibroblast Growth Factor-23 (FGF23), a bone derived hormone, in circulation are associated with renal failure. Recent studies emphasize the correlation between Heart Failure (HF) and FGF23, but the ability of cardiomyocytes themselves to express and secrete this phosphatonin is yet unknown. A further factor involved in HF is the cytokine oncostatin M (OSM). The aims of our study were: 1) to analyze the myocardium of HF patients in terms of FGF23 expression in cardiomyocytes and 2) to assess whether OSM is able to induce FGF23 production in cardiomyocytes. Methods:Cultures of adult cardiomyocytes were treated with OSM and screened for the expression of FGF23 transcripts. FGF23 secretion was determined by Western blot and ELISA of cell culture supernatants. Heart explants of HF patients with Dilated Cardiomyopathy (DCM), Ischemic Cardiomyopathy (ICM) and myocarditis (Myo) were analyzed by immunofluorescence using FGF23 antibodies and compared with healthy controls. FGF23 levels were also determined in mice with a cardiac restricted overexpression of Monocyte Chemotactic Protein-1 (MCP1), which developed an "inflammatory" Heart Failure (iHF) due to macrophage infiltration.Results: OSM massively induced the expression and secretion of FGF23 in cultured adult cardiomyocytes. Confocal microscopy revealed high amounts of FGF23 positive cardiomyocytes in the myocardium of patients with ischemic heart disease (IHD), myocarditis, dilated cardiomyopathy (DCM) and in mice with iHF. Conclusions:The presence of FGF23 in the myocardium of patients with different types of HF and in mice with "inflammatory" HF suggests that macrophages are responsible for the FGF23 expression in cardiomyocytes via OSM. Whether FGF23 acts as a regeneration promoting factor and/or potentially serves as a HF/transplantation marker has to be clarified.

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“…5,7 Increased synthesis of collagen type I with its large-diameter fibers, and/or a high degree of cross-linking may increase myocardial stiffness and alter left ventricular function. 6,8 The degradation of collagen fibers is mediated by the family of matrix metalloproteinases (MMP). 9 The product of PLAU gene, urokinase plasminogen activator (uPA) may be involved in the degradation of myocardial ECM via plasmin generation and activation of pro-MMPs.…”

Section: Ecm Proteins and Remodeling Enzymesmentioning

confidence: 99%

“…10,12,13 In humans, MMP2 and MMP14 are increased in myocardium and circulation in all types of myocardial remodeling, 6 and cardiac fibrosis with increased collagen deposition is found in endstage HF independent of etiology. 8,9,14 It was hypothesized that proteases degrade normal matrix and facilitate the deposition of a more "fibrotic" myocardial ECM. 9 All these observations suggest that enhanced COL1A2, MMP2, MMP14, and uPA expression may contribute to profibrotic properties of BMSCs isolated from non-obese HF patients.…”

Section: Ecm Proteins and Remodeling Enzymesmentioning

confidence: 99%