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Megakaryocyte DNA content is increased in patients with coronary artery atherosclerosis
P M Bath1, A M Gladwin, N Carden
1Department of Medicine, King's College School of Medicine and Dentistry, London, United Kingdom.
Insights
Megakaryocyte ploidy is elevated in patients with coronary artery atherosclerosis, correlating with disease severity and serum cholesterol. This suggests a link between hypercholesterolemia, megakaryocyte changes, and atherogenesis.
Area of Science:
- Cardiovascular Science
- Hematology
- Cell Biology
Background:
- Increased megakaryocyte size and ploidy are observed post-myocardial infarction and sudden cardiac death.
- Coronary artery atherosclerosis is a major cardiovascular disease.
Purpose of the Study:
- To compare megakaryocyte ploidy in patients with and without coronary artery atherosclerosis.
- To investigate the relationship between megakaryocyte ploidy and coronary atherosclerosis severity.
Main Methods:
- Sternal megakaryocytes were analyzed from patients undergoing cardiac surgery.
- Megakaryocytes were identified using CD41 antibody and ploidy assessed via flow cytometry.
- Coronary atherosclerosis was quantified by angiography, and serum lipid levels were measured.
Main Results:
- Megakaryocyte modal ploidy was significantly higher in patients with coronary atherosclerosis (p = 0.008).
- Ploidy correlated with the number of atherosclerotic vessels (r = 0.51, p < 0.001) and total cholesterol (r = 0.50, p = 0.006).
- Bleeding time did not differ between groups despite aspirin use in the atherosclerosis group.
Conclusions:
- Megakaryocyte ploidy is elevated in human coronary atherosclerosis.
- Hypercholesterolemia may increase megakaryocyte ploidy, potentially leading to hyperfunctional platelets and contributing to atherogenesis.
Objective:
Increased megakaryocyte size and megakaryocyte ploidy have been observed in man following myocardial infarction and sudden cardiac death. The aim of this study was to compare megakaryocyte ploidy in patients with and without coronary artery atherosclerosis.
Methods:
Sternal megakaryocytes were obtained immediately prior to cardiac surgery in 26 patients with significant coronary artery atherosclerosis requiring surgical bypass grafting and in 14 age matched control patients requiring cardiac valve replacement or repair with minimal or no coronary atherosclerosis on arteriography. Megakaryocytes were identified using a monoclonal antibody to the CD41 (GPIIb/IIIa) surface antigen and ploidy was studied using flow cytometry.
Results:
Megakaryocyte modal ploidy was significantly higher in the coronary atherosclerosis patients (modal ploidy 8N, n = 0 subjects; 16N, n = 16; 32N, n = 10) as compared with the control group (modal ploidy 8N, n = 5 subjects; 16N, n = 7; 32N, n = 2), p = 0.008. Ploidy correlated with the degree of coronary atherosclerosis defined as the number of atherosclerotic vessels observed on angiography (r = 0.51, p < 0.001, 95% confidence limits 0.25 to 0.70) and the serum total cholesterol concentration (r = 0.50, p = 0.006, 95% confidence limits 0.18 to 0.72). Bleeding time was not different [315(semiquartile range 45) s v 315(75) s] between the two groups in spite of the fact that 20 of 26 coronary atherosclerosis patients were taking aspirin versus one of 14 valve patients.
Conclusions:
Megakaryocyte ploidy is increased in human coronary atherosclerosis and correlates with serum lipids. Hypercholesterolaemia may induce increases in megakaryocyte ploidy, and hence the production of hyperfunctional platelets, which will contribute to atherogenesis.