Ceramide and Regulation of Vascular Tone

Abstract

In addition to playing a role as a structural component of cellular membranes, ceramide is now clearly recognized as a bioactive lipid implicated in a variety of physiological functions. This review aims to provide updated information on the role of ceramide in the regulation of vascular tone. Ceramide may induce vasodilator or vasoconstrictor effects by interacting with several signaling pathways in endothelial and smooth muscle cells. There is a clear, albeit complex, interaction between ceramide and redox signaling. In fact, reactive oxygen species (ROS) activate different ceramide generating pathways and, conversely, ceramide is known to increase ROS production. In recent years, ceramide has emerged as a novel key player in oxygen sensing in vascular cells and mediating vascular responses of crucial physiological relevance such as hypoxic pulmonary vasoconstriction (HPV) or normoxic ductus arteriosus constriction. Likewise, a growing body of evidence over the last years suggests that exaggerated production of vascular ceramide may have detrimental effects in a number of pathological processes including cardiovascular and lung diseases.

Circulating ceramide ratios and risk of vascular brain aging and dementia

“…5,17,[31][32][33] In a murine model of ceramide synthase 2 haploinsufficiency, a reduction in levels of very long-chain (C22:0 and C24:0) ceramides and a compensatory increase in levels of longchain ceramides (C16:0) was noted, resulting in an increased susceptibility to insulin resistance and hepatocyte apoptosis. 30 Given the role of ceramides in pancreatic b-cell dysfunction, insulin resistance and vascular reactivity, 34 increased cardiometabolic risk could potentially mediate the association with dementia. Indeed, we observed that higher levels of ceramides C24:0 and C22:0 relative to C16:0 were associated with a lower burden of white matter disease on MRI brain.…”

Plasma lipidomic analysis of sphingolipids in patients with large artery atherosclerosis cerebrovascular disease and cerebral small vessel disease

“…In the present study, we found several ceramides and SM (d34:1) were increased in age-related CSVD. Ceramides may cause endothelial dysfunction and increase the permeability of the blood-brain barrier by promoting oxidative stress, inflammation and reducing the production of nitric oxide [29][30][31], thus leading to CSVD [32]. Ceramides and sphingomyelins are components of myelin sheath in white matter, playing important roles in maintaining normal function of the myelin sheath [33].…”

The Role of Ceramides in Diabetes and Cardiovascular Disease Regulation of Ceramides by Adipokines

“…In recent years, ceramides, a subgroup of sphingolipids, have received increased attention for their role in myriad pathophysiologic mechanisms, including those underlying cancer ( 23 – 25 ), inflammation ( 26 ), depression ( 27 ), and neurodegenerative disorders ( 28 ). Additionally, more recent studies have highlighted their increasingly important role in obesity and diabetes ( 9 , 29 – 31 ) as well as cardiovascular disease (CVD) ( 32 ). Preventing aberrant ceramide deposition can prevent or ameliorate a variety of cardiometabolic pathologies, including insulin resistance, CVD (atherosclerosis, heart failure), and hepatic steatosis ( 33 , 34 ), as well as mitochondrial dysfunction ( Figure 1 ).…”