Search results for "Cardiac fibrosis"

Differential PI3K signal transduction in obesity-associated cardiac hypertrophy and response to ischemia

2014

Objective Elevated insulin and inflammatory cytokine levels in obesity may chronically activate signaling pathways regulating cardiac growth and contractility. Our aim was to examine the effect of obesity on cardiac PI3K isoform and Akt activation during left ventricular (LV) hypertrophy and heart failure. Methods Wild-type mice were fed normal chow or high-fat diet (HFD) for 2, 4, or 6 months. A subset of mice was subjected to chronic myocardial ischemia (MI). Results Echocardiography revealed a progressive increase in LV mass, wall thickness, and diameters in obese mice. Systolic pump function was not impaired. Increased cardiac levels of PI3Kγ, phosphorylated Akt, GSK3β, and Epac were ob…

2021

Growth and differentiation factor 15 (GDF15) belongs to the transforming growth factor-β (TGF-β) superfamily of proteins. Glial-derived neurotrophic factor (GDNF) family receptor α-like (GFRAL) is an endogenous receptor for GDF15 detected selectively in the brain. GDF15 is not normally expressed in the tissue but is prominently induced by “injury”. Serum levels of GDF15 are also increased by aging and in response to cellular stress and mitochondrial dysfunction. It acts as an inflammatory marker and plays a role in the pathogenesis of cardiovascular diseases, metabolic disorders, and neurodegenerative processes. Identified as a new heart-derived endocrine hormone that regulates body growth,…

Procollagen C-Proteinase Enhancer 1 (PCPE-1) is a marker of myocardial fibrosis and impaired cardiac function in a murine model of pressure overload

2021

Abstract(1)AimsProcollagen C-proteinase enhancer 1 (PCPE-1) is an extracellular matrix protein and a major regulator of fibrillar collagen biosynthesis. Previous work has shown that its abundance is often increased in the context of tissue repair and fibrosis. The present study was designed to evaluate its potential as a biomarker of myocardial interstitial fibrosis (MIF), a well-established pathogenic pathway leading to heart failure.(2)Methods and ResultsCardiac fibrosis was induced in rats using an optimized model of chronic pressure overload triggered by angiotensin II and Nω-nitro-L-arginine methyl ester (L-NAME). All treated animals suffered from heart hypertrophy and the increase in …

Is the Macrophage Phenotype Determinant for Fibrosis Development?

2021

Fibrosis is a pathophysiological process of wound repair that leads to the deposit of connective tissue in the extracellular matrix. This complication is mainly associated with different pathologies affecting several organs such as lung, liver, heart, kidney, and intestine. In this fibrotic process, macrophages play an important role since they can modulate fibrosis due to their high plasticity, being able to adopt different phenotypes depending on the microenvironment in which they are found. In this review, we will try to discuss whether the macrophage phenotype exerts a pivotal role in the fibrosis development in the most important fibrotic scenarios.

No evidence of adverse cardiac remodeling in former elite endurance athletes

2016

Background: The impact of high exercise loads on a previously healthy heart remains controversial. We examined the consequences of decades of strenuous endurance exercise at the highest competition level on heart dimensions and volumes as well as on serum biomarkers of cardiac fibrosis/remodeling. Methods and results: We compared echocardiographic measurements and serum biomarkers of cardiac fibrosis/remodeling [troponin I, galectin-3, matrix metallopeptidase-2 and -9, N-terminal pro-brain natriuretic peptide, carboxy-terminal propeptide of type I procollagen, and soluble suppressor of tumorigenicity-2 (sST-2)/interleukin(IL)-1R4] in 53 male athletes [11 former professional ('elite') and 42…

Machine Learning Identification of Pro-arrhythmic Structures in Cardiac Fibrosis

2021

Cardiac fibrosis and other scarring of the heart, arising from conditions ranging from myocardial infarction to ageing, promotes dangerous arrhythmias by blocking the healthy propagation of cardiac excitation. Owing to the complexity of the dynamics of electrical signalling in the heart, however, the connection between different arrangements of blockage and various arrhythmic consequences remains poorly understood. Where a mechanism defies traditional understanding, machine learning can be invaluable for enabling accurate prediction of quantities of interest (measures of arrhythmic risk) in terms of predictor variables (such as the arrangement or pattern of obstructive scarring). In this st…

Decrease of CD4+ T Lymphocytes after myocardial infarction is related with extensive myocardial fibrosis

2013

Purpose: Myocardial fibrosis plays a potential role in left ventricular remodeling and patients' outcome. After myocardial infarction innate immune cells infiltrate infarcted area and replace necrotic tissue by fibrotic tissue. However the role of adaptive immunity, especially T cells, has not yet been investigated in this scenario. Methods: We studied 94 patients with a first STEMI treated with percutaneous revascularization. Leucocyte subsets and a wide variety of lymphocyte subtypes were determined in peripheral blood 24 h after reperfusion by means of flow cytometry. Infarct size and cardiac fibrosis were measured by late enhancement Cardiac Magnetic Resonance (CRM) 1 week and 6 months …

Cardiac magnetic resonance-derived fibrosis, strain and molecular biomarkers of fibrosis in hypertensive heart disease

2020

Aims Myocardial fibrosis is a relevant component of hypertensive heart disease (HHD). Novel cardiovascular magnetic resonance (CMR) imaging techniques have shown potential in quantification of diffuse cardiac fibrosis, with T1 mapping, and estimating preclinical cardiac dysfunction, with strain analysis. Molecular biomarkers of fibrosis have been related with clinical outcomes and histologically proven myocardial fibrosis. The relationship between these CMR-imaging techniques and circulating biomarkers is not fully understood. Methods and results CMR was performed on a 3T scanner in 36 individuals with HHD. Extracellular volume fraction (ECV) and the partition coefficient were assessed usin…

Inhibition of Rac1 signaling by lovastatin protects against anthracycline-induced cardiac toxicity

2011

Normal tissue damage limits the efficacy of anticancer therapy. For anthracyclines, the clinically most relevant adverse effect is cardiotoxicity. The mechanisms involved are poorly understood and putative cardioprotectants are controversially discussed. Here, we show that the lipid-lowering drug lovastatin protects rat H9c2 cardiomyoblasts from doxorubicin in vitro. Protection by lovastatin is related to inhibition of the Ras-homologous GTPase Rac1. It rests on a reduced formation of DNA double-strand breaks, resulting from the inhibition of topoisomerase II by doxorubicin. Doxorubicin transport and reactive oxygen species are not involved. Protection by lovastatin was confirmed in vivo. I…