Role of oxidative and nitrosative stress biomarkers in chronic heart failure

In this review, we present recent insights on chronic heart failure (CHF) and the potential role of tumor necrosis factor (TNF)-alpha, interleukins, myeloperoxidase (MPO), and nitrosative stress in the progression of this disease process. Reactive oxygen species (ROS) are produced as a consequence of aerobic metabolism. Under physiologic conditions, their unfavourable effect in causing oxidative damage is counteracted by antioxidants. An imbalance in favour of oxidants leads to oxidative stress, and contributes to myocyte apoptosis, direct negative inotropic effects, and reduced bioavailability of nitric oxide (NO). Together, these effects lead to impaired vasodilatation of the coronary, pu…

Aerobic training and angiogenesis activation in patients with stable chronic heart failure: a preliminary report.

The pathophysiology of chronic heart failure (CHF) involves multiple hystologic and molecular alterations. To determine the effects of physical training on circulating endothelial progenitor cells (EPCs), angiogenesis (angiogenin, angiopoietin-1 and -2, VEGF, Tie-2, SDF-1α) and inflammation (IL-6, CRP), we compared data obtained from 11 CHF pts before and after 3 months aerobic exercise training, to those from 10 non trained CHF pts (CHF-C group, age 64 + 2 years, NYHA 2). At the end of the study, EPCs count and AP-2 serum levels significantly increased in the CHF-TR group. These preliminary data suggest a significant effect of even a short program of physical training on angiogenic activat…

Increased nitrotyrosine plasma levels in relation to systemic markers of inflammation and myeloperoxidase in chronic heart failure

The presence of a reciprocal link between inflammation and oxidative/nitrosative stress has been postulated in chronic heart failure (CHF). We aimed to determine signs of nitrosative stress in serum/plasma of CHF patients. ELISA tests were used for quantification of serum/plasma levels of Nitrotyrosine (NT), H(2)O(2), total NO, nitrite (NO(2)(-)), myeloperoxidase (MPO), Tumor Necrosis Factor-alpha (TNFalpha) and pro-Brain Natriuretic Peptide (proBNP) in 66 CHF patients (9 in NYHA I, 34 NYHA II, 23 NYHA III) and in 14 age-matched healthy subjects. NT levels were higher in NYHA III CHF patients compared to NYHA II (p<0.05), NYHA I (p<0.03) and controls (p<0.02), whereas NO(2)(-) and total NO …

Oxidative stress induces myeloperoxidase expression in endocardial endothelial cells from patients with chronic heart failure.

Increased oxidative stress has been implicated in the pathogenesis of a number of cardiovascular diseases. Recent findings suggest that myeloperoxidase (MPO) may play a key role in the initiation and maintenance of chronic heart failure (CHF) by contributing to the depletion of the intracellular reservoir of nitric oxide (NO). NO consumption through MPO activity may lead to protein chlorination or nitration, leading to tissue damage. Primary cultures of human endocardial endothelial cells (EEC) obtained at heart transplantation of patients with CHF and human umbilical vein endothelial cells (HUVEC) were subjected to oxidative stress by incubation with hydrogen peroxide at non lethal (60 mic…

Fibrosis markers and CRIM1 increase in chronic heart failure of increasing severity.

AbstractBackground: Fibrosis suppressors/activators in chronic heart failure (CHF) is a topic of investigation.Aim: To quantify serum levels of fibrosis regulators in CHF.Methods: ELISA tests were used to quantify fibrosis regulators, procollagen type-(PIP)I, (PIP)III, collagen-I, III, BMP1,2,3,7, SDF1α, CXCR4, fibulin 1,2,3, BMPER, CRIM1 and BAMBI in 66 CHF (NYHA class I, n = 9; II, n = 34; III n = 23), and in 14 controls.Results: In CHF, TGFβR2, PIPIII, SDF1α and CRIM1 were increased. PIPIII correlated with CRIM1.Conclusions: The BMPs inhibitor CRIM1 is increased and correlates with higher levels of serum PIPIII showing an imbalance in favor of pro-fibrotic mechanisms in CHF.

Isolation and characterization of pluripotent cells from the subendocardial layer of human hearts from chronic heart failure patients

Role of endothelial cell stress in the pathogenesis of chronic heart failure.

Endothelial cells are key modulators of diverse physiological processes, and their impaired function is a cause of numerous cardiovascular diseases. Under physiologic condition, the reactive oxygen and nitrogen mediators in endothelia lead to the signal propagation of the initial stimulus, by forming molecules with a longer half-life like hydrogen peroxide. Hydrogen peroxide is the focus of growing attention in endothelial biology, and consequently the enzymes involved in its generation and clearance are viewed as novel mediators of great importance. In particular, among peroxidases, myeloperoxidase is recognized as a key enzyme, capable of impairing intracellular NO reservoirs as well as p…