Abstract
Ceramides represent a class of biologically active lipids that are involved in orchestrating vital signal transduction pathways responsible for regulating cellular differentiation and proliferation. However, accumulating clinical evidence have shown that ceramides are playing a detrimental role in the pathogenesis of several diseases including cardiovascular disease, type II diabetes and obesity, collectively referred to as cardiometabolic disease. Therefore, it has become necessary to study in depth the role of ceramides in the pathophysiology of such diseases, aiming to tailor more efficient treatment regimens. Furthermore, understanding the contribution of ceramides to the pathological molecular mechanisms of those interrelated conditions may improve not only the therapeutic but also the diagnostic and preventive approaches of the preceding hazardous events. Hence, the purpose of this article is to review currently available evidence on the role of ceramides as a common factor in the pathological mechanisms of cardiometabolic diseases as well as the mechanism of action of the latest ceramides-targeted therapies.
Highlights
Cardiometabolic disorders is an umbrella term for a group of interrelated diseases and risk factors including cardiovascular diseases (CVDs), type II diabetes, hypercholesterolemia, and their underlying risk events such as insulin resistance, endothelial dysfunction, and atherosclerosis (Zhang et al, 2018; Miranda et al, 2019; Yang et al, 2021)
High plasma levels of specific ceramides has been linked with several conditions, including CVDs, type II diabetes, obesity, hypercholesteremia, insulin resistance, and hypertension
The pathogenesis of ceramides in cardiometabolic diseases may be partially explicated through mutual pathological mechanisms based on their inflammatory, and oxidative stress effects in addition to being the main players in the dysregulation of the PI3k/Akt pathway
Summary
Cardiometabolic disorders is an umbrella term for a group of interrelated diseases and risk factors including cardiovascular diseases (CVDs), type II diabetes, hypercholesterolemia, and their underlying risk events such as insulin resistance, endothelial dysfunction, and atherosclerosis (Zhang et al, 2018; Miranda et al, 2019; Yang et al, 2021). Researchers are constantly searching for new biomarkers to help in the early diagnosis of such diseases and ways for addressing the increasing levels of their prevalence across the world (Roberts and Gerszten, 2013). Out of these diseases, CVDs remain one of the world’s biggest killers to mankind, despite the significant advancements in related therapies (Goradel et al, 2018). Numerous limitations of using LC-MS/MS to measure ceramides still exist regarding its specificity in detecting the broad spectrum of ceramides species and derivatives, in addition to the substantial variation of these lipids among individuals depending on many factors such as age, sex, and diet (Gaggini et al, 2021)
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