Advanced glycation end products (AGEs) are independently related to cardiovascular disease (CVD) and favor cholesterol and oxysterol accumulation in macrophage foam cells. Soluble RAGE (sRAGE) impairs cellular AGE signaling alleviating the deleterious effects of AGE in atherogenesis. The association between plasma AGEs and sRAGE with the content of cholesterol, markers of cholesterol synthesis and absorption, and oxysterols in atherosclerotic plaques was evaluated in subjects undergoing carotid endarterectomy.Plasma and carotid plaques were obtained from symptomatic ( = 23) and asymptomatic subjects ( = 40). Lipids from plaques were extracted and sterols (oxysterols, cholesterol, desmosterol, lathosterol, sitosterol, and campesterol) were determined by using gas chromatography/mass spectrometry. Plasma total AGEs and pentosidine were measured by using fluorimetry and sRAGE by using ELISA.In symptomatic subjects´ atherosclerotic plaques, an increased amount of cholesterol (3x) and oxysterols [7 α-hydroxycholesterol (1.4x); 7 β-hydroxycholesterol (1.2x); 25-hydroxycholesterol (1.3x); 24-hydroxycholesterol (2.7x), and 27-hydroxycholesterol, (1.15x)], with exception to 7 ketocholesterol, were found in comparison to asymptomatic individuals. Plasma total AGEs and pentosidine significantly and positively correlated to sterols accumulated in the atherosclerotic lesion, including cholesterol, desmosterol, campesterol, sitosterol, and oxysterols. On the other hand, sRAGE inversely correlated to total AGEs and pentosidine in plasma, and with major species of oxysterols, cholesterol, and markers of cholesterol synthesis and absorption in the atherosclerotic lesion. In multiple regression analyses, it was observed a significant inverse correlation between sRAGE and 24-hydroxycholesterol and desmosterol, and a positive significant correlation between pentosidine and 24-hydroxycholesterol, 27-hydroxycholesterol, and campesterol.In conclusion, the plasma concentration of AGEs and sRAGE is a tool to predict the accumulation of sterols in atherosclerotic lesions in symptomatic and asymptomatic individuals, helping to prevent and improve the management of acute cardiovascular complications.
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http://dx.doi.org/10.1177/14791641221085269 | DOI Listing |
Burns
December 2024
Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini, Cairo 11562, Egypt.
This study focused on the potential of Gliricidia sepium (Jacq.) Kunth. ex.
View Article and Find Full Text PDFJ Clin Med
December 2024
Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina, 34100 Trieste, Italy.
Despite notable advancements in cardiovascular medicine, morbidity and mortality rates associated with myocardial infarction (MI) remain high. The unfavourable prognosis and absence of robust post-MI protocols necessitate further intervention. In this comprehensive review, we will focus on well-established and novel biomarkers that can provide insight into the processes that occur after an ischemic event.
View Article and Find Full Text PDFCancers (Basel)
December 2024
Department of Radiation Oncology, Corewell Health William Beaumont University Hospital, Royal Oak, MI 48076, USA.
Pancreatic cancer is the third leading cause of cancer-related mortality in the United States, with rising incidence and mortality. The receptor for advanced glycation end products (RAGE) and its ligands significantly contribute to pancreatic cancer progression by enhancing cell proliferation, fostering treatment resistance, and promoting a pro-tumor microenvironment via activation of the nuclear factor-kappa B (NF-κB) signaling pathways. This study validated pathway activation in human pancreatic cancer and evaluated the therapeutic efficacy of TTP488 (Azeliragon), a small-molecule RAGE inhibitor, alone and in combination with radiation therapy (RT) in preclinical models of pancreatic cancer.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
The Receptor for Advanced Glycation End Products (RAGE), part of the immunoglobulin superfamily, plays a significant role in various essential functions under both normal and pathological conditions, especially in the progression of Alzheimer's disease (AD). RAGE engages with several damage-associated molecular patterns (DAMPs), including advanced glycation end products (AGEs), beta-amyloid peptide (Aβ), high mobility group box 1 (HMGB1), and S100 calcium-binding proteins. This interaction impairs the brain's ability to clear Aβ, resulting in increased Aβ accumulation, neuronal injury, and mitochondrial dysfunction.
View Article and Find Full Text PDFArch Biochem Biophys
January 2025
Department of Biochemistry, J.N.M.C., Faculty of Medicine, Aligarh Muslim University, Aligarh 202002, U.P., India. Electronic address:
Glycation and aggregation of proteins have garnered more interest in recent years. Glycation leads to the formation of protein aggregates and advanced glycation ends (AGEs) that play crucial roles within several pathological conditions. The objective of our study is to gain a deeper understanding of the formation of AGEs and aggregates of human serum albumin (HSA) in the presence of methylglyoxal and the protective effects of the phytochemical berberine.
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