Emerging Roles of Ceramide in Cardiovascular Diseases

Abstract

Ceramide is a core molecule of sphingolipid metabolism that causes selective insulin resistance and dyslipidemia. Research on its involvement in cardiovascular diseases has grown rapidly. In resting cells, ceramide levels are extremely low, while they rapidly accumulate upon encountering external stimuli. Recently, the regulation of ceramide levels under pathological conditions, including myocardial infarction, hypertension, and atherosclerosis, has drawn great attention. Increased ceramide levels are strongly associated with adverse cardiovascular risks and events while inhibiting the synthesis of ceramide or accelerating its degradation improves a variety of cardiovascular diseases. In this article, we summarize the role of ceramide in cardiovascular disease, investigate the possible application of ceramide as a new diagnostic biomarker and a therapeutic target for cardiovascular disorders, and highlight the remaining problems.

Role of ceramides in diabetic foot ulcers (Review)

“…The different vascular effects may result from the different types of vessels and their various diameters, as well as the cell types they act on. Notably, different lengths of ceramides have different pathological functions ( 87 ).…”

“…Furthermore, previous studies have provided clear evidence that sphingolipids, particularly ceramides, have an important role in T1DM and the complications of T2DM ( 89 , 90 ). Indeed, several metabolic diseases, including DM, cardiomyopathy, insulin resistance and atherosclerosis, can be treated by preventing ceramide production or accelerating ceramide breakdown ( 87 ).…”

Sex Differences in Cardiovascular Diseases: A Matter of Estrogens, Ceramides, and Sphingosine 1-Phosphate

“…Together with SM, Cers are essential constituents of the cell membrane, participating in cell signaling regulating the localization and activation of membrane-associated receptors [ 45 ]. Cers are involved in several biological activities that influence the pathophysiology of CVDs, with effects on apoptosis, oxidative stress, inflammation, endothelial dysfunction, insulin resistance, and lipotoxicity [ 46 , 47 ]. For this reason, Cer modulation has been correlated to various pathological conditions, particularly those affecting the CV system.…”

Circulating Biomarkers for Laboratory Diagnostics of Atherosclerosis—Literature Review

“…They are synthesized by six different ceramide synthases and represent the scaffold for complex sphingolipids, e.g., sphingomyelin and the glycosphingolipids [ 41 ]. Ceramides perform important biological roles, being implicated in the signalling pathways that are associated with various cellular processes, such as cell growth, differentiation, and apoptosis [ 42 ]. They have also been shown to be involved in the pathophysiological mechanisms of a large array of human diseases, including atherosclerosis and cardiovascular disease (CVD), insulin resistance and type 2 diabetes mellitus, neurodegenerative disorders, etc.…”

“…Ceramides are produced in higher amounts in vascular endothelial cells in patients with atherosclerosis, and they lead to decreased NO (nitric oxide) production and the impairment of endothelium-derived vasorelaxation, thus contributing to the arterial dysfunction that is associated with CVD [ 50 ]. Ceramides are also involved in the chronic inflammation that is associated with the atherosclerotic process by promoting the production of C-reactive protein (CRP) and interleukin-6 (IL-6) [ 42 ].…”