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Platelet calcium homeostasis is abnormal in patients with severe arteriosclerosis
A M Vicari1, M L Monzani, F Pellegatta
1Department of Medicine, IRCCS H. San Raffaele, Milan, Italy.
Insights
Platelets in patients with severe arteriosclerosis show abnormal calcium homeostasis, with higher resting intracellular calcium and altered responses to thrombin. This suggests chronic platelet activation in this thrombosis-prone condition.
Area of Science:
- Cardiovascular Research
- Hematology
- Biochemistry
Background:
- Platelet calcium homeostasis is crucial for normal function.
- Severe arteriosclerosis is a thrombosis-prone condition associated with platelet activation.
Purpose of the Study:
- To investigate platelet calcium homeostasis in patients with severe arteriosclerosis.
- To compare intracellular calcium levels and responses to thrombin between patients and healthy controls.
Main Methods:
- Evaluated platelet intracellular free calcium concentration ([Ca2+]i) using the fluorescent probe fura 2.
- Studied 14 patients with severe arteriosclerosis and 11 healthy controls.
- Assessed calcium levels under resting conditions and after thrombin stimulation at varying extracellular calcium concentrations ([Ca2+]e).
Main Results:
- Patients exhibited significantly higher resting platelet [Ca2+]i compared to controls (P < .001).
- The relative increase in [Ca2+]i upon thrombin stimulation was generally lower in patients across different extracellular calcium levels.
- This blunted response was statistically significant at lower thrombin concentrations and specific extracellular calcium conditions.
Conclusions:
- Platelets from patients with severe arteriosclerosis display abnormal calcium homeostasis.
- These findings suggest a state of chronic activation in platelets of patients with this condition.
- Altered calcium handling may contribute to the prothrombotic state in arteriosclerosis.
Abstract:
To evaluate platelet calcium homeostasis in a typical thrombosis-prone clinical condition, 14 patients with severe arteriosclerosis and 11 healthy control subjects were studied. Platelet intracellular free calcium concentration ([Ca2+]i) was evaluated by means of the fluorescent probe fura 2 under resting conditions and after challenge with 0.05, 0.1, and 0.5 U/mL thrombin (final concentrations). Three different concentrations of extracellular ionized calcium ([Ca2+]e) were used: 1 mmol/L, 1 mumol/L, and < 1 nmol/L. Resting platelet [Ca2+]i was significantly higher (P < .001) in patients than in control subjects. After addition of 0.05 U/mL thrombin, the relative increase of [Ca2+]i was lower in patients than in control subjects in each of the three [Ca2+]e conditions (P = .05 at 1 mmol/L, P = .02 at 1 mumol/L, and P = .04 at < 1 nmol/L). After addition of 0.1 U/mL thrombin, the relative increase of [Ca2+]i was lower in patients than in control subjects under two [Ca2+]e conditions, 1 mumol/L and < 1 nmol/L (P = .04 and P = .03 respectively). With 0.5 U/mL thrombin, a trend toward lower values in patients than in control subjects was observed, reaching statistical significance (P = .03) only at < 1 nmol/L [Ca2+]e. These results suggest that calcium homeostasis is abnormal in platelets from patients with severe arteriosclerosis and probably reflects a chronic activation.