Endothelial Microparticles and Platelet and Leukocyte Activation in Patients with the metabolic Syndrome

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1 Endothelial Microparticles and Platelet and Leukocyte Activation in Patients with the metabolic Syndrome Arteaga RB, Chirinos JA, Soriano A, et al. Am J Cardiol 2006;98:70-4. Presented by Paisal Mongkolwongroj Cardiovascular Research Group Journal Club at Department of Pathology, Faculty of medicine, KKU 3 July

2 Abstract

3 The Metabolic Syndrome: Historical Perspective 1988: Syndrome X Insulin Resistance Glucose Intolerance Hyperinsulinemia TG TG HDL-C Hypertension Coronary Heart Disease Reaven G. Diabetes 1988;37:

4 Metabolic Syndrome Increases Risk for CHD and Type 2 Diabetes High LDL-C Metabolic Syndrome Type 2 Diabetes Coronary Heart Disease Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:

5 Conceptual Framework for the Metabolic Syndrome Environmental causes are responsible for the epidemic of the metabolic syndrome (NCEP, IDF, AHA/NHLBI ) Treatment: reduce obesity and increase activity Insulin resistance is the underlying cause of the metabolic syndrome (WHO) Treatment a. reduce obesity and increase activity b. insulin sensitizers Inflammation is the underlying cause of the metabolic syndrome Treatment a. reduce obesity and increase activity b. insulin sensitizers c. statins, ACE inhibitors, ARBs

6 Metabolic Syndrome: Operational Definition Many definitions WHO (1998/1999) NCEP (2001) AACE (2002) IDF (2005) AHA/NHLBI (2005)

7 Risk Factor Abdominal obesity (Waist circumference) Men Women TG HDL-C Men Women Blood pressure Fasting glucose ATP III: The Metabolic Syndrome Diagnosis is established when 3 risk factors are present: Defining Level >102 cm (>40 in) >88 cm (>35 in) 150 mg/dl <40 mg/dl <50 mg/dl 130/ 85 mm Hg 110 mg/dl Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:

8 The Metabolic Syndrome: Current Perspective Body Size BMI Central Adiposity Insulin Resistance + Hyperinsulinemia Glucose Metabolism ± Glucose intolerance Uric Acid Metabolism Uric acid Urinary uric acid clearance Dyslipidemia Hemodynamic Novel Risk Factors TG SNS activity CRP PP lipemia Na retention PAI-1 HDL-C Hypertension Fibrinogen PHLA Small, dense LDL Coronary Heart Disease Adapted from Reaven G. Drugs 1999;58(suppl):19-20 with permission from WolthersKluwer Health.

9 What is microparticle? Circulating, phospholipid-rich, Small particles (<0.1 um diameter) released from the membranes of endothelial cells, platelets, leukocytes and red blood cells

10 Microparticles formation

11 Br J Haematol 2007;137;41

12

13 Thromb Haemost 2005;94:490

14 Br J Haematol 2007;137;41

15 Br J Haematol 2007;137;42

16 Objective To mesure circulating endothelial (EMP)and platelet microparticles (PMP) and platelet-leukocyte (PLT-LEU) conjugates and endothelial-leukocytes conjugates in metabolic syndrome patients and compare with controls

17 Materials and Methods

18 Study population Patients Total 33, 18 male &19 female Obtained informed consent Controls 25 healthy volunteers Meet no MS criteria Obtained informed consent

19 Inclusion Criteria for MS patients Meet 3 or more of the criteria: BMI >29.9 kg/m 2 BP >130/85 mmhg Fasting glucose equal or >110 mg/dl HDL-cholesterol <40 mg/dl in men <50 mg/dl in men Triglyceride equal or > 150mg/dl

20 Exclusion Criteria for MS patients Familial history of CVD History of thyroid, adrenal, pituitary diseases Evidence of coronary artery disease, athero-thrombotic disease DM Cigarette smoking Arterial hypertension On hormone, aspirin and non-steroid anti-inflammatory drugs Pregnancy or on oral contraceptives

21 Blood sampling and handling Fasting blood Glucose Total cholesterol HDL-cholesterol Triglyceride etc Whole blood Expression of Leukocyte Activation marker CD11b Platelet poor plasma Flowcytometer with 2 dyes labeled

22 Anthropology and Blood pressure Height and weight were obtained BP was measured 2-brachial cuff, in sitting position with 5 min rest and taked the mean of 2 measures.

23 Measurement of microparticles CD11b P-selectin :platelet and leukocyte activation marker CD45+CD41 :platelet leukocyte conjugates CD54:adhesion molecule -endothelial marker CD31:endothelial marker CD62E: E-selectin -endothelial marker CD51:vitronectrin receptor -endothelial marker

24 Statistic analysis Man-Whitney U test or t-test Linear regression analysis Pearson correlation coefficient

25 Results

26

27

28 Discussion

29

30

31

32

33 Prothrombotic

34 J Thromb Haemost 2003;1:2566

35

36 This study found no correlation of fasting triglyceride and EMP 31.

37 Thank you for your attention

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