The modulation of the hexosamine biosynthetic pathway impacts the localization of CD36 in macrophages.

CD36 is a type 2 cell surface scavenger receptor expressed in various tissues. In macrophages, CD36 recognizes oxidized low-density lipoprotein (ox-LDL), which promotes the formation of foam cells, the first step toward an atherosclerotic arterial lesion. CD36 possesses a variety of posttranslational modifications, among them N-glycosylation and O-GlcNAc modification. Some of the roles of these modifications on CD36 are known, such as N-linked glycosylation, which provides proper folding and trafficking to the plasma membrane in the human embryonic kidney. This study aimed to determine whether variations in the availability of UDP-GlcNAc could impact Rab-5-mediated endocytic trafficking and, therefore, the cellular localization of CD36. These preliminary results suggest that the availability of the substrate UDP-GlcNAc, modulated in response to treatment with Thiamet G (TMG), OSMI-1 (O-GlcNAcylation enzymes modulators) or Azaserine (HBP modulator), influences the localization of CD36 in J774 macrophages, and the endocytic trafficking as evidenced by the regulatory protein Rab-5, between the plasma membrane and the cytoplasm.

LOX-1 in Cardiovascular Disease: A Comprehensive Molecular and Clinical Review.

LOX-1, ORL-1, or lectin-like oxidized low-density lipoprotein receptor 1 is a transmembrane glycoprotein that binds and internalizes ox-LDL in foam cells. LOX-1 is the main receptor for oxidized low-density lipoproteins (ox-LDL). The LDL comes from food intake and circulates through the bloodstream. LOX-1 belongs to scavenger receptors (SR), which are associated with various cardiovascular diseases. The most important and severe of these is the formation of atherosclerotic plaques in the intimal layer of the endothelium. These plaques can evolve into complicated thrombi with the participation of fibroblasts, activated platelets, apoptotic muscle cells, and macrophages transformed into foam cells. This process causes changes in vascular endothelial homeostasis, leading to partial or total obstruction in the lumen of blood vessels. This obstruction can result in oxygen deprivation to the heart. Recently, LOX-1 has been involved in other pathologies, such as obesity and diabetes mellitus. However, the development of atherosclerosis has been the most relevant due to its relationship with cerebrovascular accidents and heart attacks. In this review, we will summarize findings related to the physiologic and pathophysiological processes of LOX-1 to support the detection, diagnosis, and prevention of those diseases.

An Overview of Glycosylation and its Impact on Cardiovascular Health and Disease.

The cardiovascular system is a complex and well-organized system in which glycosylation plays a vital role. The heart and vascular wall cells are constituted by an array of specific receptors; most of them are N- glycosylated and mucin-type O-glycosylated. There are also intracellular signaling pathways regulated by different post-translational modifications, including O-GlcNAcylation, which promote adequate responses to extracellular stimuli and signaling transduction. Herein, we provide an overview of N-glycosylation and O-glycosylation, including O-GlcNAcylation, and their role at different levels such as reception of signal, signal transduction, and exogenous molecules or agonists, which stimulate the heart and vascular wall cells with effects in different conditions, like the physiological status, ischemia/reperfusion, exercise, or during low-grade inflammation in diabetes and aging. Furthermore, mutations of glycosyltransferases and receptors are associated with development of cardiovascular diseases. The knowledge on glycosylation and its effects could be considered biochemical markers and might be useful as a therapeutic tool to control cardiovascular diseases.