Macrophage-Specific Lipid-Based Nanoparticles Improve Cardiac Magnetic Resonance Detection and Characterization of Human Atherosclerosis
ObjectivesWe sought to determine whether gadolinium (Gd)-containing lipid-based nanoparticles (NPs) targeting the macrophage scavenger receptor-B (CD36) improve cardiac magnetic resonance (CMR) detection and characterization of human atherosclerosis.BackgroundGd-containing lipid-based NPs targeting macrophages have improved MR detection of murine atherosclerosis.MethodsGadolinium-containing untargeted NPs, anti-CD36 NPs, and nonspecific Fc-NPs were created. Macrophages were incubated with fluorescent targeted and nontargeted NPs to determine uptake via confocal microscopy and inductively coupled plasma mass spectroscopy (ICP-MS) quantified Gd uptake. Human aortic specimens were harvested at…
Lipidomic profiling identifies signatures of metabolic risk
Background: Metabolic syndrome (MetS), the clustering of metabolic risk factors, is associated with cardiovascular disease risk. We sought to determine if dysregulation of the lipidome may contribute to metabolic risk factors. Methods: We measured 154 circulating lipid species in 658 participants from the Framingham Heart Study (FHS) using liquid chromatography-tandem mass spectrometry and tested for associations with obesity, dysglycemia, and dyslipidemia. Independent external validation was sought in three independent cohorts. Follow-up data from the FHS were used to test for lipid metabolites associated with longitudinal changes in metabolic risk factors. Results: Thirty-nine lipids were…
Beta-3 adrenergic receptor overexpression reverses aortic stenosis-induced heart failure and restores balanced mitochondrial dynamics
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Impact of Oxidative Stress on the Heart and Vasculature
Abstract Vascular disease and heart failure impart an enormous burden in terms of global morbidity and mortality. Although there are many different causes of cardiac and vascular disease, most causes share an important pathological mechanism: oxidative stress. In the failing heart, oxidative stress occurs in the myocardium and correlates with left ventricular dysfunction. Reactive oxygen species (ROS) negatively affect myocardial calcium handling, cause arrhythmia, and contribute to cardiac remodeling by inducing hypertrophic signaling, apoptosis, and necrosis. Similarly, oxidative balance in the vasculature is tightly regulated by a wealth of pro- and antioxidant systems that orchestrate r…