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Platelet sialic acid as a potential pathogenic factor in coronary heart disease
Robert Mandic1, Claus Opper, Jürgen Krappe
1Department of Otorhinolaryngology, Head and Neck Surgery, Philipps University Marburg, Deutschhausstrasse 3, D-35037 Marburg, Germany. mandic@mailer.uni-marburg.de
Insights
Patients with coronary heart disease (CHD) have fewer negatively charged sialic acids on their platelets, leading to increased platelet aggregation and a higher risk of heart disease.
Area of Science:
- Biochemistry
- Hematology
- Cardiovascular Science
Background:
- Patients with coronary heart disease (CHD) show increased platelet aggregation.
- The underlying reasons for this heightened aggregation in CHD patients were previously unknown.
- Platelet surface charge, influenced by sialic acid, may play a role in cell interactions.
Purpose of the Study:
- To investigate if reduced platelet sialic acid content is a pathogenic factor in coronary heart disease (CHD).
- To determine the relationship between sialic acid levels and platelet aggregation in CHD patients.
Main Methods:
- Platelets were isolated from patients with CHD and healthy controls.
- The proportion of low-density platelets was quantified.
- Sialic acid content on platelet surfaces was measured.
- Neuraminidase susceptibility was assessed to determine sialic acid localization.
Main Results:
- A higher proportion of low-density platelets was observed in CHD patients compared to controls.
- Platelets from CHD patients exhibited significantly lower sialic acid content.
- Sialic acid was predominantly located on the outer surface of platelets, as indicated by neuraminidase sensitivity.
Conclusions:
- Lower sialic acid content on platelets may contribute to increased platelet aggregation in CHD patients.
- Reduced negative surface charge due to lower sialic acid levels could diminish platelet repulsion, facilitating aggregation.
- This finding suggests a potential mechanism linking platelet surface chemistry to cardiovascular disease pathogenesis.
Abstract:
It was previously reported that, compared to healthy individuals, patients with coronary heart disease (CHD) exhibit a higher proportion of platelets with lower densities and higher propensity to aggregate. Reasons for this increased tendency to aggregate were unknown but appeared to be independent of the patient's age, gender, or smoking habits. Sialic acid (N-acetyl-neuraminic acid), a negatively charged sugar and constituent of many glycoproteins and gangliosides, is known to confer the bulk of negative charges to mammalian cell surfaces. These negatively charged surfaces can help cells of the bloodstream to maintain a relative distance from each other due to repulsion of the same (negative) charges. In this study, we examined whether differences in platelet sialic acid are a potential pathogenic factor in patients with coronary heart disease. Upon isolating platelets, we found a significantly higher (p < 0.05) proportion of low density platelets in patients compared to healthy controls, which is in accordance with previously published data. We found significantly less (p < 0.05) sialic acid in platelets from patients compared to the control. Most of the platelet total sialic acid was susceptible to cleavage by neuraminidase, demonstrating sialic acid to be preferably localized at the outer platelet surface. We conclude that the lower sialic acid content found in platelets from CHD patients could represent a contributing factor for the observed higher aggregability of platelets from these patients. Due to the lower sialic acid content and resulting lower negative surface charge, less repulsion between the platelets could facilitate aggregation.