Circulating microparticles as indicators of peripartum cardiomyopathy.

AIMS Peripartum cardiomyopathy (PPCM) is associated with high mortality and morbidity. Endothelial damage involving cathepsin-D to form a 16 kDa prolactin (PRL) peptide is pathogenetically relevant. Inhibiting PRL peptide with bromocriptine has yielded promising results. We investigated whether microparticles (MPs) can be quantified in serum as markers for diagnosis and treatment effects in PPCM. METHODS AND RESULTS Patients with PPCM were compared with age-matched healthy post-partum women (PPCTR), healthy pregnant women (PCTR), healthy non-pregnant women (NPCTR), patients with ischaemic cardiomyopathy (ICM), patients with stable coronary artery disease (CAD) and healthy controls (HCTR). Peripartum cardiomyopathy treated with bromocriptine (PPCM-BR) and with PPCM without bromocriptine-treatment as control (PPCM-BRCTR) were compared. Microparticles were determined by flow cytometry. Endothelial MPs (EMPs) were elevated in PPCM compared with PPCTR, PCTR, and NPCTR, each P< 0.001. They were significantly elevated compared with ICM, CAD, and HCTR (P< 0.001). Pregnancy (PCTR) exhibited only slight increases vs. ICM, CAD, NPCTR, and HCTR. The increase in PPCM was due to an increase of activated but not apoptotic EMPs. Platelet-derived microparticles were highly increased in PPCM compared with ICM (P< 0.001) but 9.3 ± 4.4-fold compared with CAD (P< 0.001). In NPCTR (P< 0.001) compared with NPCTR, the increase was 5.9 ± 1.7-fold (P< 0.001). Microparticles generated from monocytes (MMPs) were increased 2.4 ± 1.8-fold in PPCM compared with PCTR (P< 0.001) and 4.8 ± 3.6-fold compared with CAD (P< 0.001), whereas leucocyte MPs (LMPs) were not significantly elevated. Endothelial microparticles were significantly reduced in PPCM treated additionally with bromocriptine compared with PPCM treated only with heart failure therapy (P< 0.001). CONCLUSION Microparticle profiles may in long-term distinguish PPCM from normal pregnancy, heart failure, and vascular diseases and might be a diagnostic marker related to the pathomechanism of PPCM.

[1]  N. Norton,et al.  Rare Variant Mutations in Pregnancy-Associated or Peripartum Cardiomyopathy , 2010, Circulation.

[2]  C. O'connor,et al.  Usefulness of soluble and surface-bound P-selectin in detecting heightened platelet activity in patients with congestive heart failure. , 1999, The American journal of cardiology.

[3]  Shing‐Jong Lin,et al.  The prognostic value of circulating soluble cell adhesion molecules in patients with chronic congestive heart failure , 2003, European journal of heart failure.

[4]  M. Gollob,et al.  Frequency of peripartum cardiomyopathy. , 2006, The American journal of cardiology.

[5]  R. Lang,et al.  A modified definition for peripartum cardiomyopathy and prognosis based on echocardiography. , 1999, Obstetrics and gynecology.

[6]  G. Nickenig,et al.  Circulating CD 31 1 / Annexin V 1 microparticles correlate with cardiovascular outcomes , 2011 .

[7]  B. Horne,et al.  Birthing the genetics of peripartum cardiomyopathy. , 2010, Circulation.

[8]  K. Sliwa,et al.  Peripartum cardiomyopathy: inflammatory markers as predictors of outcome in 100 prospectively studied patients. , 2006, European heart journal.

[9]  R. Andriantsitohaina,et al.  Shed membrane particles from preeclamptic women generate vascular wall inflammation and blunt vascular contractility. , 2006, The American journal of pathology.

[10]  U. Elkayam,et al.  Pregnancy-Associated Cardiomyopathy: Clinical Characteristics and a Comparison Between Early and Late Presentation , 2005, Circulation.

[11]  P. Brunet,et al.  Endothelial-derived microparticles: Biological conveyors at the crossroad of inflammation, thrombosis and angiogenesis , 2010, Thrombosis and Haemostasis.

[12]  C. Vrints,et al.  Flow cytometric detection of endothelial microparticles (EMP): effects of centrifugation and storage alter with the phenotype studied. , 2010, Thrombosis research.

[13]  K. Sliwa,et al.  Current state of knowledge on aetiology, diagnosis, management, and therapy of peripartum cardiomyopathy: a position statement from the Heart Failure Association of the European Society of Cardiology Working Group on peripartum cardiomyopathy , 2010, European journal of heart failure.

[14]  H. Ogawa,et al.  Significance of a multiple biomarkers strategy including endothelial dysfunction to improve risk stratification for cardiovascular events in patients at high risk for coronary heart disease. , 2009, Journal of the American College of Cardiology.

[15]  D. Hilfiker-Kleiner,et al.  Disease-modifying Mutations in Familial Hypertrophic Cardiomyopathy Complexity from Simplicity Article P 1820 Editorial , 2022 .

[16]  P. Rickenbacher,et al.  Incidence of myocarditis in peripartum cardiomyopathy. , 1994, The American journal of cardiology.

[17]  Françoise Dignat-George,et al.  The Many Faces of Endothelial Microparticles , 2011, Arteriosclerosis, thrombosis, and vascular biology.

[18]  U. Elkayam,et al.  Peripartum Cardiomyopathy , 2016, Lancet.

[19]  M. Alessi,et al.  Microparticles of human atherosclerotic plaques enhance the shedding of the tumor necrosis factor-alpha converting enzyme/ADAM17 substrates, tumor necrosis factor and tumor necrosis factor receptor-1. , 2007, The American journal of pathology.

[20]  K. Sliwa,et al.  A Cathepsin D-Cleaved 16 kDa Form of Prolactin Mediates Postpartum Cardiomyopathy , 2007, Cell.

[21]  K. Sliwa,et al.  Spectrum of heart disease and risk factors in a black urban population in South Africa (the Heart of Soweto Study): a cohort study , 2008, The Lancet.

[22]  J. Hsia,et al.  Peripartum Cardiomyopathy: National Heart, Lung, and Blood Institute and Office of Rare Diseases (National Institutes of Health) Workshop Recommendations and Review , 2000 .

[23]  T. Douchi,et al.  Chylous vaginal discharge in a patient with lymphangioleiomyomatosis. , 2008, American journal of obstetrics and gynecology.

[24]  M. Haubitz,et al.  Detection of circulating microparticles by flow cytometry: influence of centrifugation, filtration of buffer, and freezing , 2010, Vascular health and risk management.

[25]  R. Bertina,et al.  Pre-analytical and analytical issues in the analysis of blood microparticles , 2010, Thrombosis and Haemostasis.

[26]  L. Horstman,et al.  Platelet microparticles: a wide-angle perspective. , 1999, Critical reviews in oncology/hematology.

[27]  L. Christie,et al.  Five-year prospective study of the incidence and prognosis of peripartum cardiomyopathy at a single institution. , 2005, Mayo Clinic proceedings.

[28]  Mike Kirby,et al.  Guidelines on the management of cardiovascular diseases during pregnancy The Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology ( ESC ) , 2011 .

[29]  G. Lip,et al.  Assessment of endothelial damage and dysfunction: observations in relation to heart failure. , 2003, QJM : monthly journal of the Association of Physicians.

[30]  S. Rahimtoola,et al.  Peripartum Cardiomyopathy , 1971, Circulation.

[31]  L. Horstman,et al.  Elevation of endothelial microparticles, platelets, and leukocyte activation in patients with venous thromboembolism. , 2005, Journal of the American College of Cardiology.

[32]  W. Paulus,et al.  Peripartum Cardiomyopathy as a Part of Familial Dilated Cardiomyopathy , 2010, Circulation.

[33]  L. Horstman,et al.  Endothelial cells release phenotypically and quantitatively distinct microparticles in activation and apoptosis. , 2003, Thrombosis research.

[34]  C. Ludlam,et al.  Plasma microparticles and vascular disorders , 2007, British journal of haematology.

[35]  Circulating endothelial progenitor cells and cardiovascular outcomes. , 2005 .

[36]  K. Sliwa,et al.  Evaluation of Bromocriptine in the Treatment of Acute Severe Peripartum Cardiomyopathy: A Proof-of-Concept Pilot Study , 2010, Circulation.

[37]  P. Holme,et al.  Shear-induced platelet activation and platelet microparticle formation in native human blood. , 1998, Thrombosis research.

[38]  B. Pieske,et al.  Peripartum Cardiomyopathy—A New Treatment Option by Inhibition of Prolactin Secretion , 2009 .

[39]  S. Pfister Role of Platelet Microparticles in the Production of Thromboxane by Rabbit Pulmonary Artery , 2004, Hypertension.

[40]  Roeland M. H. Merks,et al.  Endothelial microparticles affect angiogenesis in vitro: role of oxidative stress. , 2005, American journal of physiology. Heart and circulatory physiology.

[41]  A. Simon,et al.  Endothelial microparticles in diseases , 2008, Cell and Tissue Research.

[42]  E. vanBavel,et al.  Vascular function in preeclampsia. , 2000, Cardiovascular research.

[43]  A. Tedgui,et al.  Role of microparticles in atherothrombosis , 2008, Journal of internal medicine.

[44]  J. Moodley,et al.  Peripartum Cardiomyopathy: Experiences at King Edward VIII Hospital, Durban, South Africa and a Review of the Literature , 1995, Tropical doctor.

[45]  H. Drexler,et al.  Recovery from postpartum cardiomyopathy in 2 patients by blocking prolactin release with bromocriptine. , 2007, Journal of the American College of Cardiology.