Abstract-Oxidative stress plays an important role in the development of cardiac remodeling after myocardial infarction (MI), but the sources of oxidative stress remain unclear. We investigated the role of Nox2-containing reduced nicotinamide-adenine dinucleotide phosphate oxidase in the development of cardiac remodeling after MI. Adult Nox2 Ϫ/Ϫ mice exhibited less cardiomyocyte hypertrophy, apoptosis, and interstitial fibrosis; reduced increases in expression of connective tissue growth factor and procollagen 1 mRNA; and smaller increases in myocardial matrix metalloproteinase-2 activity than WT mice. These data suggest that the Nox2-containing reduced nicotinamide-adenine dinucleotide phosphate oxidase contributes significantly to the processes underlying adverse cardiac remodeling and contractile dysfunction post-MI. Key Words: NADPH oxidase Ⅲ cardiac remodeling Ⅲ reactive oxygen species Ⅲ fibrosis Ⅲ hypertrophy M yocardial infarction (MI) is the most common cause of heart failure in developed countries. Heart failure develops because of adverse post-MI cardiac remodeling, a process that involves progressive changes in structure and function of the extracellular matrix and cardiomyocytes in the noninfarcted myocardium and results in significant left ventricular (LV) cavity dilatation, interstitial fibrosis, myocyte hypertrophy, and depressed contractile function. 1 Reactive oxygen species (ROS) production and oxidative stress are increased after both experimental and clinical MI, and growing evidence supports an important role for this in the processes underlying cardiac remodeling post-MI. 2 ROS modulate several of the processes underlying cardiac remodeling, such as the activation and expression of matrix metalloproteinases (MMPs), interstitial fibrosis, and myocyte hypertrophy. [3][4][5] In addition, experimental reduction in ROS levels can attenuate remodeling post-MI, eg, after chronic treatment with dimethylthiourea 6 or transgenic overexpression of glutathione peroxidase. 7 The sources of ROS production and the mechanisms by which they influence cardiac remodeling post-MI remain unclear. Recent studies indicate that a major ROS source in the heart is a family of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases. 8 -13 The prototypic NADPH oxidase is composed of a membrane-bound het-
Pulmonary hypertension is defined as a mean arterial pressure of ≥25 mmHg as confirmed on right heart catheterisation. Traditionally, the pulmonary arterial systolic pressure has been estimated on echo by utilising the simplified Bernoulli equation from the peak tricuspid regurgitant velocity and adding this to an estimate of right atrial pressure. Previous studies have demonstrated a correlation between this estimate of pulmonary arterial systolic pressure and that obtained from invasive measurement across a cohort of patients. However, for an individual patient significant overestimation and underestimation can occur and the levels of agreement between the two is poor. Recent guidance has suggested that echocardiographic assessment of pulmonary hypertension should be limited to determining the probability of pulmonary hypertension being present rather than estimating the pulmonary artery pressure. In those patients in whom the presence of pulmonary hypertension requires confirmation, this should be done with right heart catheterisation when indicated. This guideline protocol from the British Society of Echocardiography aims to outline a practical approach to assessing the probability of pulmonary hypertension using echocardiography and should be used in conjunction with the previously published minimum dataset for a standard transthoracic echocardiogram.
Background-Left ventricular (LV) mechanical dyssynchrony (LVMD) has emerged as a therapeutic target using cardiac resynchronization therapy (CRT) in selected patients with chronic heart failure.
The Nox2 oxidase contributes to the development of cardiac contractile dysfunction and interstitial fibrosis during pressure overload, although it is not essential for development of morphologic hypertrophy per se. These data suggest divergent downstream effects of Nox2 on different components of the overall response to pressure overload.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.