Platelet-neutrophil conjugate formation is increased in diabetic women with cardiovascular disease
Hillary A Tuttle1, Grace Davis-Gorman, Steven Goldman
1Cardiovascular and Thoracic Surgery and The Sarver Heart Center, University of Arizona Health Sciences Center, Tucson, AZ 85724, USA. tuttleh@comcast.net
Insights
Diabetic women show increased platelet-neutrophil activation, a marker linked to cardiovascular disease (CVD). This heightened response in diabetic women may explain their greater risk for coronary heart disease (CHD) compared to men.
Area of Science:
- Cardiovascular Science
- Diabetology
- Immunology
Background:
- Diabetes affects over 17 million Americans, increasing coronary heart disease (CHD) risk fourfold.
- Diabetic women face a 3.8 times higher risk of CHD than diabetic men, with underlying reasons unclear.
- Increased platelet-neutrophil conjugates, associated with cardiovascular disease (CVD), are hypothesized to be higher in diabetic women with CVD.
Purpose of the Study:
- To test if platelet-neutrophil conjugates are elevated in diabetic women with CVD compared to diabetic men with CVD and non-diabetic women with CVD.
- To investigate the inflammatory response and platelet-neutrophil interactions in diabetic women with cardiovascular disease.
Main Methods:
- Quantification of platelet-neutrophil conjugates using flow cytometry.
- Assessment of direct binding between neutrophil PSGL-1 receptor and platelet P-selectin.
- Stimulation of blood samples with platelet-activating factor (PAF).
Main Results:
- Diabetic women without CVD showed increased platelet-neutrophil conjugates (63.3%) upon PAF stimulation compared to diabetic women with CVD (46.8%) and non-diabetic women with CVD (48.6%).
- The stimulation ratio of platelet-neutrophil conjugates was significantly higher in diabetic and non-diabetic women with CVD (3.3) versus diabetic men with CVD (2.1).
Conclusions:
- Platelets and neutrophils in diabetic women exhibit a greater activation potential than in diabetic men.
- This enhanced activation may contribute to increased thrombosis and inflammation.
- Findings suggest a potential mechanism for the higher severity of coronary heart disease observed in diabetic women.
Background:
More than seventeen million Americans are afflicted with diabetes and these people have four times the rate of coronary heart disease (CHD) as non-diabetics. Furthermore, diabetic women have a 3.8 fold greater risk for CHD compared to diabetic men. Little is known why diabetic women are at an increased risk for CHD. It is possible that diabetic women with cardiovascular disease (CVD) have a greater inflammatory response resulting in an increased platelet neutrophil conjugate formation than diabetic men with CVD or non-diabetic women with CVD. This study tested the hypothesis that platelet-neutrophil conjugates, which are associated with several cardiovascular diseases, are increased in diabetic women with CVD compared to diabetic men with CVD and non-diabetic women with CVD.
Methods:
Platelet-neutrophil conjugates were quantified by flow cytometry. The primary method is through direct binding of the neutrophil PSGL-1 receptor with P-selectin expressed on the platelet.
Results:
In this study, we found when the blood was stimulated with PAF (platelet activating factor), diabetic women without CVD demonstrated an increase in platelet-neutrophil conjugates compared to diabetic women with CVD and non-diabetic women with CVD (% conjugates: 63.3 +/- 5.2 vs 46.8 +/- 4.3 vs 48.6 +/- 3.4, p < 0.05). The stimulation ratio was significantly increased in diabetic and non-diabetic women with CVD in comparison to diabetic men with CVD (ratio: 3.3 +/- 0.4 vs 3.3 +/- 0.3 vs 2.1 +/- 0.3, p < 0.05).
Conclusion:
These results suggest that platelets and neutrophils in diabetic women have a greater potential for activation compared to diabetic men and may contribute to thrombosis/inflammation and the greater severity of coronary heart disease observed in diabetic women as compared to diabetic men.
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