Role of Ceramides in the Molecular Pathogenesis and Potential Therapeutic Strategies of Cardiometabolic Diseases: What we Know so Far

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.

Identification of a Specific Plasma Sphingolipid Profile in a Group of Normal-Weight and Obese Subjects: A Novel Approach for a “Biochemical” Diagnosis of Metabolic Syndrome?

“…Thus, the vascular tone is maintained by a balance between Cer and S1P, without ruling out other sphingolipids or different species of the same sphingolipid, which, so far, have not been fully investigated in terms of vaso-regulation [ 66 ]. These arguments may not only explain the results of the present study, but also open new areas of research for the treatment of blood hypertension [ 67 ].…”

Ceramides during Pregnancy and Obstetrical Adverse Outcomes

“…From a structural point of view, they consist of an 18-carbon-amino-alcohol backbone, usually sphingosine, linked via an amide bond to a fatty acid chain [2]. The latter can vary in terms of saturation and length, encompassing medium (12)(13), long (16)(17)(18), very long (20)(21)(22)(23)(24), and ultra-long (>26) carbon atoms [3]. The number of structurally unique ceramides exceeds 1500; novel molecules are discovered due to the continuous development of analytic techniques [4,5].…”

“…These responses render them relevant to many diseases. Ceramides potentially contribute to the pathogenesis of various autoimmune conditions, including rheumatic diseases and psoriasis, and cardiovascular and metabolic disorders, such as insulin resistance, diabetes, and gestational diabetes [2,6,[19][20][21][22][23][24][25][26]. Emerging evidence suggests an association with cancer through epigenetic mechanisms and psychiatric disorders [27,28].…”

Ceramides: correlation with cardiovascular risk factors

“…Первоначально клинические исследования церамидов были направлены на выявление пациентов высокого риска среди лиц с установленной ИБС в целях вторичной профилактики [7,8] Обнаружено, что соотношения церамидов (С(16:0)/(24:0), С(18:0)/(24:0) и С(24:1)/(24:0)) связаны с риском развития неблагоприятных CCC независимо от ХС-ЛПНП и традиционных факторов риска ИБС [10].…”