Introduction
References | Possible mechanism of ↓ pMV concentration | |
---|---|---|
ASA | COX-1 inhibition | |
ADP receptor inhibitors | P2Y12 receptor inhibition, increase intraplatelet concentration of cAMP | |
PDE inhibitors | PDE3/PDE5 inhibition, increase cAMP concentration | |
GP IIb/IIIa antagonists | GP IIb/IIIa inhibition | |
Heparin | [29] | Mediation of an attractive interaction between phospholipid membranes |
Statins | Rho-kinase pathway, activation of PPARs, reduction of NF-κB activity | |
Fibrates | Activation of PPAR-α, increase cAMP and cGMP concentration, COX-1 inhibition, inhibition of Ca2+ concentration | |
PUFAs | Substrates for COX and competition with AA, incorporation into the phospholid cell membrane | |
Hypoglycemic agents | Adiponectin-dependent and NO-dependent pathway | |
Calcium channel blockers | Calcium influx inhibition and decrease intracellular calcium concentration, PPAR activation | |
Low-calorie diet | Decrease level of leptin |
Platelet-Derived Microvesicles
Release of Platelet-Derived Microparticles
Properties of Platelet-Derived Microvesicles
Methods of pMV Measurement
The Impact of Pharmacological Modulation on Platelet-Derived Microvesicles
Antiplatelet Therapy
Irreversible Cyclooxygenase Inhibitors
Adenosine Diphosphate Receptor Inhibitors
Phosphodiesterase Inhibitors
GP IIb/IIIa Antagonists
Other Antiplatelet Agents
Anticoagulants
Heparins
Vitamin K Antagonist
Others
Hypolipemic Therapy
HMG-CoA Reductase Inhibitors (Statins)
Fibrates
Inhibitors of Cholesterol Intestinal Absorption
Other Hypolipidemic Treatment
Hypoglycemic Therapy
Antihypertensive Therapy
Non-Pharmacological Interventions
Summary
Population/disease | Treatment strategy/dose and duration | Effect on pMV concentration | Reference | Supplementary information | |
---|---|---|---|---|---|
COX inhibitors: ASA | Healthy subjects | 100 mg/day for 3 or 7 days | ↓ | [18] | ↓ ADP-induced pMV formation |
Healthy volunteers | 100 mg/day for 7 days | No effect | [87] | ||
Hypertensive heart disease and non-significant (< 50% lumen narrowing) CAD | Chronic treatment (8 weeks) with a dose of 100 mg/day | ↓ | [9] | ||
Acute ischemic stroke | No data available | No effect | [6] | SP | |
TIA, ischemic stroke, multi-infarct dementia | No data available | No effect | [7] | SP | |
Chronic phase of ischemic stroke | 100 mg/day for 4 weeks | No effect | [8] | SP | |
AF | 150 mg/day for 4 weeks | No effect | [81] | PP | |
Diabetes | 100 mg/day for 10 or 15 days | No effect | PP | ||
Patients after ACS | 75 mg/day for 6 months | No effect | [41] | SP | |
PAOD and hypercholesterolemia | 320 mg/day for 8 weeks | No effect | [86] | PP | |
Diabetes | No data available | No effect | [13] | ||
Stable CAD | 100 mg/day for 1 week | No effect | [84] | ||
CAD patients undergoing coronary angioplasty | No data available | No effect | [85] | ||
ADP receptor inhibitors | Healthy subjects | 75 mg/day clopidogrel for 3 days | ↓ | [18] | ↓ ADP-induced pMV formation |
Healthy volunteers | Administration of a loading dose (60 mg) of prasugrel | ↓ | [86] | in vitro study | |
Stable CAD | 75 mg/day clopidogrel for 3 weeks | ↓ | [19] | Negative correlation between clopidogrel plasma concentration and pMV release | |
ACS patients | Clopidogrel (loading dose of 600 mg followed by a maintenance dose of 75 mg/day) for 30 days | ↓ | [88] | high-on clopidogrel platelet reactivity associated with higher pMV concentration SP | |
ACS patients | Clopidogrel and subcutaneous LMWH (i.e., enoxaparin 1 mg per kg body weight twice daily) | ↓ | [41] | SP | |
ACS treated with PCI | Oral loading dose of ASA (500 mg) and clopidogrel (600 mg), then DAPT (75 mg/day ASA and 75 mg/day clopidogrel) for 12 months | ↓ | [20] | pMV concentration higher in patients with high platelet reactivity (assessed by impedance aggregometry); SP | |
PDE inhibitors | Chronic phase of ischemic stroke | 200 mg/day cilostazol for 4 weeks | No effect | [8] | SP |
Arteriosclerosis obliterans | 100 mg/day cilostazol for 2 weeks or combined therapy with cilostazol (100 mg/day) and dipyridamole (150 mg/day) for 14 weeks | ↓ | [93] | ↓ pMV number (more significant on combined therapy) | |
Non-insulin-dependent diabetes | 150 mg/day cilostazol for 4 weeks | ↓ | [22] | ||
Diabetes with nephropathy | 150 mg cilostazol | ↓ | [23] | ||
Acute ischemic stroke | combined therapy with cilostazol (200 mg/day) and ASA (100 mg/day) for 4 weeks | ↓ | [24] | SP | |
ITP patient with ischemic stroke | Combined therapy with 200 mg/day cilostazol and prednisolone (30 mg/day) for 30 days | ↓ | [95] | Elevation of pMV concentration after decrease in prednisolone dose | |
Combined therapy with dexamethasone (40 mg/day for 4 days), prednisolone (30 mg/day), and cyclosporine (250 mg/day) for 1 month | ↓ | Revision of immunosupressive therapy resulted in normalization of plasma pMV SP | |||
GP IIb/IIIa inhibitors | Medication-free normal volunteers | Abciximab (10 μg/mL, approximately 0.2 μm) | ↓ | [25] | In vitro study |
Healthy donors | Abciximab | ↓ | [26] | ||
Medication-free normal volunteers | 0.5 μm tirofiban or 0.5 μm eptifibatide | No effect | [25] | In vitro study No effect as a result of eptifibatide shorter half-life and reduced affinity for the receptor | |
STEMI after PCI | Abciximab (one 250 μg/kg bolus followed by 0.125 μg/kg/min continuous infusion up to 12 h) plus standard DAPT (ASA + clopidogrel) | ↓ | [27] | SP | |
STEMI after PCI | Eptifibatide (one 180 μg/kg bolus followed by 2 μg/kg/min continuous infusion up to 18 h) plus standard DATP (ASA + clopidogrel) | No effect | [27] | No effect as a result of eptifibatide shorter half life and reduced affinity for the receptor SP | |
NSTEMI | Eptifibatide (180 μg/kg IV bolus, followed by an infusion of 2 μg/kg per min) given in addition to ASA (500 mg bolus IV followed by 75 mg/day orally), enoxaparin (1 mg/kg twice a day subcutaneously), and clopidogrel (oral loading dose 300 mg) | ↓ | [28] | SP | |
Anticoagulants | DVT | Long-term (for 3 months) anticoagulant therapy with a LMWH-tinzaparin (175 IU/kg per day) | ↓ | [105] | The decrease of procoagulant activity of MV |
DVT | Vitamin K antagonist—acenocoumarol for 3 months | ↑ | [105] | The increase of procoagulant activity of MV | |
Non-valvular AF | Oral anticoagulation with vitamin K antagonist, warfarin (with the target range for INR, 2 to 3) | No effect | [81] | PP | |
Statins | PAOD | Combined therapy with atorvastatin (80 mg/day) and ASA (320 mg/day) for 8 weeks | ↓ Exposition of TF, P-selectin, GPIIIa on pMVs | [86] | |
Hypercholesterolemic patients | Different statins: simvastatin (20 mg/day), atorvastatin (20 mg/day), or rosuvastatin (10 mg/day) | ↓ | [111] | Compare to untreated patients with the same plasma lipid level PP | |
Hypertensive and hyperlipidemic patients with type 2 diabetes | Combined therapy simvastatin (10 mg/day) and losartan (50 mg/day) for 24 weeks | ↓ | [114] | ||
Hyperlipidemic patients after ischemic stroke confirmed by CT | Simvastatin 20 mg/day for 6 months | ↓ | [30] | SP | |
CAD | Withdrawal of rosuvastatin (rosuvastatin was given at daily dose of 40 mg and clopidogrel loading dose was 300 mg, followed by 75 mg daily) | ↓ | [31] | Increase of pMV amount after rosuvastatin withdrawal | |
Hyperlipidemic, diabetic patients | Pitavastatin 2 mg/day for 6 months | No effect | [93] | ||
Hyperlipidemic, diabetic patients | Combined therapy with pitavastatin (2 mg/day) and EPA (1800 mg/day) for 6 months | ↓ | [93] | ||
Diabetes type 1 with dyslipidemia | Atorvastatin (80 mg/day) for 2 months | ↓ Exposition of surface markers | [116] | ↓ Exposition of GPIIIa, P-selectin on pMVs PP | |
Diabetic patients with or without chronic kidney disease | Simvastatin 40 mg/day for 8–10 weeks | ↓ Exposition of surface markers | [32] | ↓ P-selectin, CD40L exposition on pMVs PP | |
Type 2 diabetes | Pravastatin 40 mg/day for 8 weeks | ↓ Exposition of surface markers No effect on pMV concentration | [117] | ↓ Exposition of GPIIIa receptor for fibrinogen on pMVs | |
Fibrates | Patients with connective tissue diseases and secondary hyperlipidemia caused by long-term steroid administration | 6-month treatment with bezafibrate | ↓ | [33] | |
Patients with diabetes without obstructive CAD | 400 mg/day bezafibrate for 6 weeks | ↓ | [34] | PP | |
Intestinal cholesterol absorption inhibitors | Diabetic patients with or without chronic kidney disease | Simvastatin (40 mg/day) and ezetimibe (10 mg/day) for 8–10 weeks | No effect | [32] | No further effect on pMV formation compared to simvastatin therapy alone PP |
Patients with stable CAD | 10 mg/day ezetimibe for 1 week | No effect | [84] | ||
Subjects with CAD risk factors receiving concomitant therapy with simvastatin and ezetimibe | 10 mg/day ezetimibe for 4 weeks | No effect | [122] | PP | |
Omega-3 PUFA | Healthy males and females | Single dose of EPA-rich (providing 1 g EPA with an EPA/DHA ratio of 5:1) or DHA-rich (providing 1 g DHA with an EPA/DHA ratio of 1:5) oil | No effect | [134] | Newly released pMV have reduced procoagulant properties, no effect on pMV number |
Hyperlipidemic patients with type 2 diabetes | EPA 1800 mg daily for 6 months or combined therapy with pitavastatin (2 mg/day) and EPA (1800 mg/day) for 6 months | ↓ | [93] | Higher reduction than that observed with EPA alone | |
Patients after myocardial infarction | Long-lasting (over 12 weeks) administration of EPA and DHA | ↓ | [36] | Normalization of both elevated concentration as well as TF-dependent procoagulant activity of pMV SP | |
Hyperlipidemic patients with type 2 diabetes | EPA (1800 mg/day) for 4 weeks | ↓ | [37] | ||
Hypoglycemic therapy | Diabetes type 2 with or without hemodialysis treatment | Teneligliptin 20 mg/day for 6 months | ↓ | [39] | |
Patients with type 2 diabetes | Miglitol 150 mg/day for 4 months | ↓ | [38] | ||
Diabetic patients | Acarbose 300 mg/day for 3 months | ↓ | [40] | ||
Diabetic patients | Miglitol 30 mg/day for 3 months | ↓ | [127] | ||
Antihypertensive therapy | Patients with recurrent TIA | Nifedipine (30–60 mg) for 1–6 weeks | ↓ | [7] | SP |
Patients after ACS | Different calcium channel antagonists for 6 months | ↓ | [41] | ↓ pMV number (compared to those not receiving such treatment) SP | |
Hypertensive, diabetic patients | Losartan 50 mg/day for 24 weeks | ↓ | [114] | ||
Hypertensive, hyperlipidemic patients with or without diabetes | Losartan (50 mg/day) and simvastatin (10 mg/day) for 24 weeks | ↓ | [114] | ↓ pMV percentage (greater among those with than without type 2 diabetes) | |
Hypertensive patients with diabetes type 2 | Nifedipine 50 mg/day for 12 months | ↓ | [42] | ||
Hypertensive patients with diabetes type 2 | Long-acting nifedipine formulation 20 mg/day for 6 months | ↓ | [43] | ||
Hypertensive patients with or without diabetes | Efonidipine 40 mg/day for 8 weeks | ↓ | [44] | ||
Hypertensive patients | Eprosartan 600 mg/day | ↓ | [132] | ||
Animal model of hypertension | Spironolactone | ↓ | [133] | ||
Non-pharmacological interventions | Healthy men | Two consecutive high-fat meals (900 kcal) at time point t = 0 and 4 h (breakfast and lunch); each meal consisted of 50 g of fat, of which 60% was saturated, 55 g of carbohydrates, and 30 g of protein within 15 min | ↑ | [141] | |
Animal model (rat) | High-fat diet (providing 60% of energy as fat) for 20 weeks | ↑ | [142] | ↑ Total MV number significant ↑ pMV number | |
Obese (BMI > 25 kg/m2) | Reducing calorie intake with as well as without aerobic physical exercise [mean daily caloric intake approximately 1200 kcal/day ♀, 1680 kcal/day ♂ with or without aerobic exercise 3 days per week (60 min per session)] | ↓ | [14] | A mean weight loss of 8 kg in moderately obese subjects (mean BMI = 27.4 kg/m2) | |
Obese women (BMI > 30 kg/m2) | Short-term very-low-calorie diet (600 kcal/day for 1 month and then 1200 kcal/day during the second month) | ↓ | [45] | ↓ Procoagulant pMV percentage | |
Omega-3 PUFA | Healthy males and females | Single dose of EPA-rich (providing 1 g EPA with an EPA/DHA ratio of 5:1) or DHA-rich (providing 1 g DHA with an EPA/DHA ratio of 1:5) oil | No effect | [134] | Newly released pMVs have reduced procoagulant properties, no effect on pMV number |
Hyperlipidemic patients with type 2 diabetes | EPA 1800 mg daily for 6 months or combined therapy with pitavastatin (2 mg/day) and EPA (1800 mg/day) for 6 months | ↓ | [93] | Higher reduction than that observed with EPA alone | |
Patients after myocardial infarction | Long-lasting (over 12 weeks) administration of EPA and DHA | ↓ | [36] | Normalization of both elevated concentration as well as TF-dependent procoagulant activity of pMV SP | |
Hyperlipidemic patients with type 2 diabetes | EPA (1800 mg/day) for 4 weeks | ↓ | [37] |