Printable Poly(3,4-ethylenedioxythiophene)-Based Conductive Patches for Cardiac Tissue Remodeling.

Myocardial cardiopathy is one of the highest disease burdens worldwide. The damaged myocardium has little intrinsic repair ability, and as a result, the distorted muscle loses strength for contraction, producing arrhythmias and fainting, and entails a high risk of sudden death. Permanent implantable conductive hydrogels that can restore contraction strength and conductivity appear to be promising candidates for myocardium functional recovery.

Endotrophin, a Collagen VI Formation-Derived Peptide, in Heart Failure.

Background: Endotrophin, a collagen type VI-derived peptide, mediates metabolic dysregulation, inflammation, and fibrosis in animal models, but has not been studied in human heart failure (HF).

Methods: We examined the association between circulating endotrophin and outcomes in participants suffering from HF with preserved ejection fraction (HFpEF) enrolled in the TOPCAT trial (n=205). Associations were validated in a participant-level meta-analysis (n=810) that included participants with HFpEF from the PHFS study (United States; n=174), PEOPLE cohort (New Zealand; n=168), a randomized trial of vasodilator therapy (United States; n=45), a cohort from Donostia University Hospital and University of Navarra (Spain; n=171), and the TRAINING-HF trial (Spain; n=47).

Cardiorenal interaction and heart failure outcomes. A role for insulin-like growth factor binding protein 2?

Introduction And Objectives: Preliminary results suggest that high circulating insulin-like growth factor binding protein 2 (IGFBP2) levels are associated with mortality risk in heart failure (HF) patients. As IGFBP2 levels are increased in patients with chronic kidney disease (CKD), which is associated with a higher mortality risk in HF patients, we examined whether IGFBP2 is associated with CKD in HF patients, and whether CKD modifies the prognostic value of this protein in HF patients.

Methods: HF patients (n=686, mean age 66.

Combination of Circulating Type I Collagen-Related Biomarkers Is Associated With Atrial Fibrillation.

Background: A combination of circulating biomarkers associated with excessive myocardial collagen type-I cross-linking or CCL+ (i.e., decreased carboxy-terminal telopeptide of collagen type-I to matrix metalloproteinase-1 ratio) and with excessive myocardial collagen type-I deposition or CD+ (i.

Circulating Long Noncoding RNA LIPCAR Predicts Heart Failure Outcomes in Patients Without Chronic Kidney Disease.

The plasma levels of long noncoding RNA LIPCAR are elevated in heart failure (HF) patients with reduced ejection fraction and associated with left ventricular remodeling and poor outcomes. We studied whether the presence of chronic kidney disease (CKD), as defined by an estimated glomerular filtration rate value <60mL/(min·1.73m2) modified the associations of plasma LIPCAR with left ventricular remodeling and outcomes in HF patients.

CT-1 (Cardiotrophin-1)-Gal-3 (Galectin-3) Axis in Cardiac Fibrosis and Inflammation.

Myocardial fibrosis is a main contributor to the development of heart failure (HF). CT-1 (cardiotrophin-1) and Gal-3 (galectin-3) are increased in HF and associated with myocardial fibrosis. The aim of this study is to analyze whether CT-1 regulates Gal-3.

Phenotyping of myocardial fibrosis in hypertensive patients with heart failure. Influence on clinical outcome.

Objective: Myocardial fibrosis is associated with alterations in the cross-linking and deposition of collagen type I (CCL and CD, respectively). We aimed to evaluate whether the combination of circulating biomarkers of CCL [the carboxy-terminal telopeptide of collagen type I to matrix metalloproteinase-1 ratio (CITP : MMP-1)] and CD [the carboxy-terminal propeptide of procollagen type I (PICP)] identifies myocardial fibrosis phenotypes with distinct clinical outcome in hypertensive patients with heart failure.

Methods: Endomyocardial biopsies and blood samples from 38 patients (small cohort), and blood samples from 203 patients (large cohort) were analyzed.

Role of Myocardial Collagen in Severe Aortic Stenosis With Preserved Ejection Fraction and Symptoms of Heart Failure.

Introduction And Objectives: We investigated the anatomical localization, biomechanical properties, and molecular phenotype of myocardial collagen tissue in 40 patients with severe aortic stenosis with preserved ejection fraction and symptoms of heart failure.

Methods: Two transmural biopsies were taken from the left ventricular free wall. Mysial and nonmysial regions of the collagen network were analyzed.

Myocardial Collagen Cross-Linking Is Associated With Heart Failure Hospitalization in Patients With Hypertensive Heart Failure.

Background: Excessive myocardial collagen cross-linking (CCL) determines myocardial collagen's resistance to degradation by matrix metalloproteinase (MMP)-1 and interstitial accumulation of collagen fibers with impairment of cardiac function.

Objectives: This study sought to investigate whether CCL and a newly identified biomarker of this alteration are associated with hospitalization for heart failure (HHF) or cardiovascular death in patients with HF and arterial hypertension in whom other comorbidities were excluded.

Methods: Endomyocardial biopsies and blood samples from 38 patients (invasive study), and blood samples from 203 patients (noninvasive study) were analyzed.

Association of cystatin C with heart failure with preserved ejection fraction in elderly hypertensive patients: potential role of altered collagen metabolism.

Objectives: Cystatin C has been shown to be associated with heart failure with preserved ejection fraction (HFPEF). In addition, myocardial fibrosis has been involved in diastolic dysfunction in HFPEF. Therefore, we hypothesized that increased cystatin C levels may be associated with altered collagen metabolism, contributing to diastolic dysfunction in patients with HFPEF.

Circulating Biomarkers of Myocardial Fibrosis: The Need for a Reappraisal.

Myocardial fibrosis impairs cardiac function, in addition to facilitating arrhythmias and ischemia, and thus influences the evolution and outcome of cardiac diseases. Its assessment is therefore clinically relevant. Although tissue biopsy is the gold standard for the diagnosis of myocardial fibrosis, a number of circulating biomarkers have been proposed for the noninvasive assessment of this lesion.

Galectin-3 and histological, molecular and biochemical aspects of myocardial fibrosis in heart failure of hypertensive origin.

Aims: The aim of this study was to investigate whether galectin-3 (Gal-3) is associated with myocardial histological and molecular parameters related to fibrosis and with the circulating biomarkers of the extracellular generation of mature fibril-forming collagen types I (C-terminal propeptide of procollagen type I, PICP) and III (N-terminal propeptide of procollagen type III, PIIINP) in two independent studies of hypertensive patients with heart failure (HF).

Methods And Results: Endomyocardial biopsies and blood samples from 39 HF patients (invasive study), and blood samples from 220 HF patients (non-invasive study) were analysed. Necropsies (n = 7) and blood samples (n = 20) from healthy subjects were used as controls.

Association of cardiotrophin-1 with myocardial fibrosis in hypertensive patients with heart failure.

Cardiotrophin-1 has been shown to be profibrogenic in experimental models. The aim of this study was to analyze whether cardiotrophin-1 is associated with left ventricular end-diastolic stress and myocardial fibrosis in hypertensive patients with heart failure. Endomyocardial biopsies from patients (n=31) and necropsies from 7 control subjects were studied.

Osteopontin-mediated myocardial fibrosis in heart failure: a role for lysyl oxidase?

Aims: We investigated whether the pro-fibrotic matricellular protein osteopontin (OPN) is associated with the enzymes involved in the extracellular synthesis of fibril-forming collagen type I (i.e. procollagen C-proteinase, PCP) and its cross-linking to form insoluble fibrils (i.

Collagen cross-linking but not collagen amount associates with elevated filling pressures in hypertensive patients with stage C heart failure: potential role of lysyl oxidase.

We investigated whether the quality of myocardial collagen associates with elevated left-sided filling pressures in 38 hypertensive patients with stage C chronic heart failure. Filling pressures were assessed invasively measuring pulmonary capillary wedge pressure. Left ventricular chamber stiffness constant was calculated from the deceleration time of the early mitral filling wave.

Filling pressures and collagen metabolism in hypertensive patients with heart failure and normal ejection fraction.

This study was designed to evaluate the association between circulating biomarkers of collagen metabolism and elevated left-sided filling pressures (FPs), as assessed from elevated estimated pulmonary capillary wedge pressure (ePCWP), in hypertensive patients with heart failure with normal ejection fraction. Echocardiography was performed and ePCWP was calculated from the formula ePCWP=1.90+1.

Phospholipase Cbeta4 isozyme is expressed in human, rat, and murine heart left ventricles and in HL-1 cardiomyocytes.

Phospholipase C-beta (PLCbeta) isozymes (PLCbeta(1) and PLCbeta(3)) have been extensively characterized in cardiac tissue, but no data are available for the PLCbeta(4) isozyme. In this study, PLCbeta((1-4)) isozymes mRNA relative expression was studied by real-time PCR (RT-PCR) in human, rat, and murine left ventricle and the presence of PLCbeta(4) isozyme at the protein level was confirmed by Western blotting in all species studied. Confocal microscopy experiments carried out in HL-1 cardiomyocytes revealed a sarcoplasmic subcellular distribution of PLCbeta(4).

Association of plasma cardiotrophin-1 with stage C heart failure in hypertensive patients: potential diagnostic implications.

Cardiotrophin-1 is a cytokine that induces hypertrophy and dysfunction in cardiomyocytes and has been shown to be increased in hypertensive patients. The objective of this study was to evaluate the association of cardiotrophin-1 with heart failure (HF) in hypertensive patients and its usefulness as a biomarker of stage C heart failure. Hypertensive patients without cardiac abnormalities (stage A, n = 64), with left ventricular hypertrophy (LVH) (stage B, n = 58), and with left ventricular hypertrophy and clinical manifestations of chronic heart failure (stage C, n = 39) were studied.

Impact of treatment on myocardial lysyl oxidase expression and collagen cross-linking in patients with heart failure.

The aim of this study was to investigate whether torasemide modifies collagen cross-linking in the failing human heart. We analyzed the degree of cross-linking and the expression of the enzyme lysyl oxidase, which regulates cross-linking, in the myocardium of patients with chronic heart failure at baseline and after 8 months of treatment with either torasemide or furosemide in addition to their standard heart failure therapy. Whereas lysyl oxidase protein expression was very scarce in normal hearts, it was highly expressed in failing hearts.

Association of depressed cardiac gp130-mediated antiapoptotic pathways with stimulated cardiomyocyte apoptosis in hypertensive patients with heart failure.

Objective: To investigate whether the glycoprotein (gp130)-mediated survival pathway, which protects cardiomyocytes from apoptosis, is depressed in left ventricular hypertrophy hypertensive patients with chronic heart failure.

Methods: Transvenous endomyocardial biopsies were obtained in 52 hypertensive patients with left ventricular hypertrophy: 28 without heart failure and 24 with heart failure. gp130 and gp130-dependent antiapoptotic pathways p42/44 mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) as well as gp130 agonist cardiotrophin-1 were analyzed by reverse transcriptase-polymerase chain reaction and western blot.

Upregulation of myocardial Annexin A5 in hypertensive heart disease: association with systolic dysfunction.

Aims: To investigate whether Annexin A5 (AnxA5) is related to hypertensive heart disease (HHD) and whether this relation is dependent of apoptosis.

Methods And Results: Hypertensives without cardiac abnormalities (stage A), with left ventricular hypertrophy (LVH) (stage B), and with LVH and clinical manifestations of chronic HF (stage C), were studied. AnxA5 was quantified in endomyocardial biopsies by real time RT-PCR, Western blot, and immunohistochemistry, and apoptosis by DNA fragmentation, caspase-3 activation, and PARP and Bax/Bcl-2 ratios.

Identification of a potential cardiac antifibrotic mechanism of torasemide in patients with chronic heart failure.

Objectives: This study sought to investigate whether torasemide inhibits the enzyme involved in the myocardial extracellular generation of collagen type I molecules (i.e., procollagen type I carboxy-terminal proteinase [PCP]).

[Altered fibrillar collagen metabolism in hypertensive heart failure. Current understanding and future prospects].

Arterial hypertension induces numerous alterations in the composition of cardiac tissue, which, in turn, result in structural remodeling of the myocardium. This remodeling is due to a range of pathologic mechanisms associated with mechanical, neurohormonal and cytokine processes that affect both cardiomyocyte and non-cardiomyocyte compartments of the myocardium. One of these processes involves disruption of the equilibrium between the synthesis and degradation of type-I and type-III collagen molecules.

Alterations in the pattern of collagen deposition may contribute to the deterioration of systolic function in hypertensive patients with heart failure.

Objectives: We sought to assess the distribution of collagen deposits and collagen degradation in hypertensive patients with either systolic heart failure (SHF) or diastolic heart failure (DHF).

Background: Increased collagen synthesis and deposition have been described in the myocardium of heart failure (HF) hypertensive patients.

Methods: We studied 39 HF hypertensive patients subdivided into two groups: 16 with SHF and 23 with DHF.