Related Experiment Videos
Platelet cytosolic calcium concentration, plasma lipids and hypertension
K H Le Quan Sang1, J Levenson, A Simon
1Pharmacology Section, Necker Medical School, Rene Descartes University, Paris, France.
Insights
High blood pressure and high plasma triacylglycerols are linked to increased platelet cytosolic calcium concentration. These factors may influence platelet calcium handling, potentially facilitating cell stimulation.
Area of Science:
- Cardiovascular Physiology
- Biochemistry
- Membrane Biophysics
Background:
- Platelet cytosolic calcium concentration is crucial for cellular function.
- Hypertension and hyperlipidaemia are significant cardiovascular risk factors.
- Alterations in platelet membrane dynamics may play a role in these conditions.
Purpose of the Study:
- To investigate the relationship between hypertension, hyperlipidaemia, and platelet cytosolic calcium.
- To examine the impact of altered membrane dynamics on platelet calcium handling.
- To determine if plasma factors influence platelet calcium concentrations.
Main Methods:
- Measured basal cytosolic calcium in platelets from hypertensive and normotensive subjects.
- Assessed membrane microviscosity using fluorescence depolarization.
- Loaded platelets with Quin-2 to buffer intracellular calcium and determined cytosolic calcium levels under varying extracellular calcium conditions.
Main Results:
- Cytosolic calcium concentration significantly increased with diastolic blood pressure and plasma triacylglycerols.
- Multiple regression analysis confirmed an independent relationship between cytosolic calcium, diastolic blood pressure, and triacylglycerols.
- The association between cytosolic calcium and membrane microviscosity was dependent on blood pressure and triacylglycerol levels.
Conclusions:
- Confirms a direct link between blood pressure and platelet cytosolic calcium concentration.
- Suggests plasma triacylglycerols modulate platelet calcium storage and/or extrusion mechanisms.
- These findings may explain how hypertension and hyperlipidaemia facilitate platelet activation.
Objective:
To study the relationship between high blood pressure and hyperlipidaemia and the cytosolic calcium concentration in unstimulated platelets, focusing on the effects of an alteration in membrane dynamics.
Materials And Methods:
Basal cytosolic calcium concentrations were determined in the presence and the absence of a significant calcium influx in platelets of 47 untreated hypertensive patients and 26 normotensive subjects. Membrane microviscosity was investigated by fluorescence depolarization of diphenylhexatriene and trimethylaminodiphenylhexatriene. To study the influence of plasma factors, unstimulated platelets were loaded in the presence of plasma with Quin-2, which forms a relatively strong intracellular calcium buffer. The cytosolic calcium concentration was then determined at two extracellular calcium concentrations (1 mmol/l and in the absence of a Ca2+ influx).
Results:
Irrespective of the external calcium concentration, the cytosolic calcium concentration increased significantly with diastolic blood pressure (P = 0.026 in the presence and P = 0.003 in the absence of Ca2+ influx) and with plasma triacylglycerols (P = 0.03 and 0.001, respectively). Multiple regression analysis indicated that the cytosolic Ca+ concentration was independently related to these two factors [Ca2+ = 35 + (18.6 +/- 4.6). In triacylglycerols (mmol/l) + (0.45 +/- 0.15) mmHg diastolic blood pressure; P < 0.001]. The relationship between the cytosolic calcium concentration and diphenylhexatriene or trimethylaminodiphenylhexatriene anisotropies was not independent of blood pressure and plasma triacylglycerol levels.
Conclusions:
The present results confirm the link between blood pressure and the platelet cytosolic calcium concentration and indicate that plasma triacylglycerols directly or indirectly modulate the ex vivo efficacy of platelet calcium storage and/or extrusion mechanisms. They could facilitate cell stimulation.