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Biochemical and functional alterations associated with hypercholesterolemia in platelets from hypertensive patients
M M Mazeaud1, F Driss, K H Le Quan Sang
1Pharmacology, CNRS 1482, Necker Medical School, Paris, France.
Insights
High cholesterol in hypertensive patients alters platelet function, reducing cyclic AMP and aggregation. This impacts platelet fatty acid composition, potentially contributing to atherosclerotic vascular disease.
Area of Science:
- Cardiovascular Medicine
- Platelet Biology
- Lipid Metabolism
Background:
- Hypercholesterolemia and hypertension are key risk factors for atherosclerotic vascular disease.
- Abnormal platelet function is implicated in atherogenesis.
Purpose of the Study:
- To investigate the effects of hypercholesterolemia on platelet lipid composition and reactivity in hypertensive patients.
- To determine if elevated cholesterol levels alter platelet function in the context of hypertension.
Main Methods:
- Twenty-nine untreated hypertensive patients were grouped by plasma cholesterol levels (normal, borderline, elevated).
- Platelet lipid composition, cytosolic Ca2+ concentration, cyclic AMP content, and aggregation responses to ADP and collagen were analyzed.
- Platelet fatty acid composition, including polyunsaturated to saturated fatty acid ratio, was assessed.
Main Results:
- Elevated cholesterol patients showed reduced platelet cyclic AMP and aggregation responses to ADP and collagen.
- Significant alterations in platelet fatty acid composition were observed, including increased palmitic acid and decreased polyunsaturated fatty acids.
- The polyunsaturated to saturated fatty acid ratio was significantly lowered in hypercholesterolemic hypertensive patients.
Conclusions:
- Hypercholesterolemia in hypertensive patients is associated with significant changes in platelet fatty acid composition, cyclic AMP levels, and aggregation.
- These platelet alterations differ from those seen with in vitro cholesterol loading.
- The observed changes may reflect adaptations to hemodynamic stress and lipid metabolism imbalances, potentially influencing atherogenesis.
Abstract:
Hypercholesterolemia and hypertension are two of the major risk factors associated with increased atherosclerotic vascular disease. An abnormal platelet function is one of the mechanisms proposed to participate in atherogenesis. This study was undertaken to find out whether hypercholesterolemia in hypertensive patients can change platelet lipid composition and reactivity. Twenty-nine untreated hypertensive patients were distributed into 3 age, body mass index and blood pressure-matched groups according to their plasma cholesterol levels (normal, borderline or elevated, group NC, BC and HC respectively). Their platelet lipid composition, cytosolic Ca2+ concentration, cyclic AMP content and aggregating response to ADP and collagen were determined. Platelet from group HC patients were characterized by reduced cyclic AMP content (evaluated in the presence and absence of a platelet phosphodiesterase inhibitor) and aggregating responses to ADP and collagen, increased palmitic acid content and decreased arachidonic, eicosapentaenoic and docosatetraenoic and pentaenoic acid content, resulting in a lowered polyunsaturated to saturated fatty acid ratio (P less than 0.001). In contrast, platelet cytosolic Ca2+ concentration, DPH steady-state anisotropy and cholesterol to phospholipid molar ratio were not significantly changed. This indicates that hypercholesterolemia is accompanied in hypertensive patients by marked changes in platelet fatty acid composition, cyclic AMP content and response to aggregating agents. These changes, which clearly differ from those induced by in vitro cholesterol loading, could reflect not only the balance between LDL and HDL stimulation but also an adaptation to hemodynamic perturbations.