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The Dark Side of Sphingolipids: Searching for Potential Cardiovascular Biomarkers
Paola Di Pietro1, Carmine Izzo1, Angela Carmelita Abate1
1Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, 84081 Baronissi, Italy.
Insights
Bioactive sphingolipids, like ceramides and sphingosine-1-phosphate (S1P), are increasingly linked to cardiovascular diseases (CVDs). Monitoring their levels may improve disease assessment and guide new therapeutic strategies.
Area of Science:
- Biochemistry
- Cardiology
- Metabolic Diseases
Background:
- Cardiovascular diseases (CVDs) are a leading global cause of mortality.
- Bioactive sphingolipids, particularly ceramides and sphingosine-1-phosphate (S1P), are implicated as key contributors to CVDs.
- Aberrant sphingolipid expression correlates with CVD risk factors and disease progression.
Purpose of the Study:
- To comprehensively review the role of sphingolipids in cardiovascular, cerebrovascular, and metabolic diseases.
- To highlight the latest experimental and clinical findings on sphingolipids in disease.
- To explore sphingolipids as potential prognostic indicators and therapeutic targets.
Main Methods:
- Review of experimental in vivo models demonstrating the impact of inhibiting ceramide synthesis.
- Analysis of human studies correlating circulating sphingolipid levels with disease prognosis.
- Synthesis of current literature on sphingolipid metabolism and its relevance to cardiovascular health.
Main Results:
- Pharmacological inhibition of ceramide synthesis in vivo prevents conditions like diabetes, atherosclerosis, hypertension, and heart failure.
- Circulating sphingolipid levels show potential as prognostic indicators for various diseases.
- Sphingolipid alterations are linked to cardiovascular, cerebrovascular, and metabolic disease progression.
Conclusions:
- Monitoring sphingolipid levels can enhance the assessment of cardiovascular disease progression and severity.
- Sphingolipids represent a promising target for future therapeutic interventions in cardiovascular and cerebrovascular diseases.
- Manipulating the sphingolipid pathway, by inhibiting key metabolic enzymes, offers a potential treatment strategy.
Abstract:
Cardiovascular diseases (CVDs) are the leading cause of death and illness in Europe and worldwide, responsible for a staggering 47% of deaths in Europe. Over the past few years, there has been increasing evidence pointing to bioactive sphingolipids as drivers of CVDs. Among them, most studies place emphasis on the cardiovascular effect of ceramides and sphingosine-1-phosphate (S1P), reporting correlation between their aberrant expression and CVD risk factors. In experimental in vivo models, pharmacological inhibition of de novo ceramide synthesis averts the development of diabetes, atherosclerosis, hypertension and heart failure. In humans, levels of circulating sphingolipids have been suggested as prognostic indicators for a broad spectrum of diseases. This article provides a comprehensive review of sphingolipids' contribution to cardiovascular, cerebrovascular and metabolic diseases, focusing on the latest experimental and clinical findings. Cumulatively, these studies indicate that monitoring sphingolipid level alterations could allow for better assessment of cardiovascular disease progression and/or severity, and also suggest them as a potential target for future therapeutic intervention. Some approaches may include the down-regulation of specific sphingolipid species levels in the circulation, by inhibiting critical enzymes that catalyze ceramide metabolism, such as ceramidases, sphingomyelinases and sphingosine kinases. Therefore, manipulation of the sphingolipid pathway may be a promising strategy for the treatment of cardio- and cerebrovascular diseases.
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