Atherosclerosis is characterized by the accumulation of lipids within the arterial wall. Although activation of TRPV1 cation channels by capsaicin may reduce lipid storage and the formation of atherosclerotic lesions, a clinical use for capsaicin has been limited by its chronic toxicity. Here we show that coupling of copper sulfide (CuS) nanoparticles to antibodies targeting TRPV1 act as a photothermal switch for TRPV1 signaling in vascular smooth muscle cells (VSMCs) using near-infrared light. Upon irradiation, local increases of temperature open thermo-sensitive TRPV1 channels and cause Ca2+ influx. The increase in intracellular Ca2+ activates autophagy and impedes foam cell formation in VSMCs treated with oxidized low-density lipoprotein. In vivo, CuS-TRPV1 allows photoacoustic imaging of the cardiac vasculature and reduces lipid storage and plaque formation in ApoE−/− mice fed a high-fat diet, with no obvious long-term toxicity. Together, this suggests CuS-TRPV1 may represent a therapeutic tool to locally and temporally attenuate atherosclerosis.
Age‐associated obesity and muscle atrophy (sarcopenia) are intimately connected and are reciprocally regulated by adipose tissue and skeletal muscle dysfunction. During ageing, adipose inflammation leads to the redistribution of fat to the intra‐abdominal area (visceral fat) and fatty infiltrations in skeletal muscles, resulting in decreased overall strength and functionality. Lipids and their derivatives accumulate both within and between muscle cells, inducing mitochondrial dysfunction, disturbing β‐oxidation of fatty acids, and enhancing reactive oxygen species (ROS) production, leading to lipotoxicity and insulin resistance, as well as enhanced secretion of some pro‐inflammatory cytokines. In turn, these muscle‐secreted cytokines may exacerbate adipose tissue atrophy, support chronic low‐grade inflammation, and establish a vicious cycle of local hyperlipidaemia, insulin resistance, and inflammation that spreads systemically, thus promoting the development of sarcopenic obesity (SO). We call this the metabaging cycle. Patients with SO show an increased risk of systemic insulin resistance, systemic inflammation, associated chronic diseases, and the subsequent progression to full‐blown sarcopenia and even cachexia. Meanwhile in many cardiometabolic diseases, the ostensibly protective effect of obesity in extremely elderly subjects, also known as the ‘obesity paradox’, could possibly be explained by our theory that many elderly subjects with normal body mass index might actually harbour SO to various degrees, before it progresses to full‐blown severe sarcopenia. Our review outlines current knowledge concerning the possible chain of causation between sarcopenia and obesity, proposes a solution to the obesity paradox, and the role of fat mass in ageing.
Inflammation triggered by oxidative stress is the main determinant of atherosclerotic plaque disruption, which is the leading cause of myocardial infarctions and strokes. Hence, noninvasive mapping of alterations in redox status in vivo is highly desirable for accurate assessment of plaque inflammatory activity and vulnerability. Herein, two types of near-infrared fluorescence probes, specific for glutathione (GSH)/hydrogen peroxide (H2O2) redox couple, were used to introduce the self-assembly of bovine serum albumin (BSA), forming a BSA-Cy-Mito nanoprobe for in vivo photoacoustic imaging of redox status. Such BSA-based self-assemblies on one hand processed good biocompatibility and long blood circulation for high EPR effect and plaque accumulation and on the other hand displayed strong GSH- and H2O2-dependent absorbance at 765 and 680 nm, which enabled simultaneous photoacoustic detection of GSH/H2O2 with high specificity and sensitivity. Using BSA-Cy-Mito as an in vivo GSH/H2O2 indicator, accurate detection of the redox-related inflammatory process was realized both in oxidized low-density lipoprotein (ox-LDL)-activated macrophages and high fat diet-fed apolipoprotein E-deficient (ApoE–/–) mice. Systemic administration of BSA-Cy-Mito further enabled differentiation of vulnerable plaques from stable ones based on their different redox states. Therefore, this sensitive redox-responsive PA nanoprobe may be a powerful tool for early identification of rupture-prone plaques and help in implementing successful preventative therapeutic strategies.
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.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.