sphingosine-1-phosphate and Cardiomyopathies

In recent years, the role of sphingolipids in physiology and pathophysiology of the heart attracted much attention. Ceramide was found to be involved in the pathogenesis of cardiac dysfunction in animal models of ischemia/reperfusion injury, Type 2 diabetes and lipotoxic cardiomyopathy. On the other hand, another member of this lipid family, namely sphingosine-1-phosphate, has been shown to possess potent cardioprotective properties. This chapter provides a review of the role of ceramide and other bioactive sphingolipids in physiology and pathophysiology of the heart. We describe the role of PPARs and exercise in regulation of myocardial sphingolipid metabolism. We also summarize the present state of knowledge on the involvement of ceramide and sphingosine-1-phosphate in the development and prevention of ischemia/reperfusion injury of the heart. In the last section of this chapter we discuss the evidence for a role of ceramide in myocardial lipotoxicity.

Topics: Animals; Cardiomyopathies; Ceramides; Diabetes Mellitus, Type 2; Dietary Fats; Disease Models, Animal; Exercise; Heart Failure; Humans; Lysophospholipids; Mice; Myocardial Reperfusion Injury; Myocardium; Obesity; Peroxisome Proliferator-Activated Receptors; Rats; Rats, Zucker; Receptors, Lysosphingolipid; Second Messenger Systems; Sphingolipids; Sphingosine

In recent years, the role of sphingolipids in pathophysiology of the heart attracted much attention. Ceramide was found to be involved in the pathogenesis of cardiac dysfunction in animal models of ischemia/reperfusion injury, type 2 diabetes and lipotoxic cardiomyopathy. On the other hand, sphingosine-1-phosphate (S1P), has been shown to possess potent cardioprotective properties. The aim of the present study was to examine plasma concentrations of major sphingolipids in patients with chronic heart failure (HF).. The subjects were divided into two major groups: 1) with chronic systolic HF (n=47), and 2) healthy age-matched controls (n=15). Patients in the former group were further divided according to the underlying cause of HF (ischemic heart disease or idiopathic dilated cardiomyopathy, n=29 and 18, respectively).. Plasma concentrations of S1P, sphinganine-1-phosphate and ceramide observed in both groups of HF patients were very close to these noted in the healthy controls, and no statistically significant differences were found. However, the level of free sphingosine and sphinganine in the plasma of patients with HF decreased by 25 and 27%, respectively, as compared to the control subjects. This effect was independent from the underlying cause of HF as the mean concentrations of these sphingoid bases in patients with ischemic and idiopathic HF were virtually the same.. We conclude that chronic heart failure is associated with decreased concentration of free sphingoid bases in the plasma. However, despite lower availability of substrates required for synthesis of cardioprotective sphingoid base-1 phosphates, their plasma level remains stable.

Topics: Cardiomyopathies; Ceramides; Female; Heart Failure, Systolic; Humans; Lysophospholipids; Male; Middle Aged; Sphingosine