title: Role for staphylococci in misguided thrombus resolution of chronic thromboembolic pulmonary hypertension.
abstract: OBJECTIVE
  Acute pulmonary emboli usually resolve within 6 months. However, in 0.1% to 3.8% of cases thrombus transforms into fibrous masses. If vascular obstruction is severe, the resulting condition is chronic thromboembolic pulmonary hypertension (CTEPH). Patients who carry ventriculo-atrial (VA-) shunts for the treatment of hydrocephalus and report a history of shunt infection are at an increased risk for CTEPH. Because CTEPH lacks traditional plasmatic risk factors for venous thromboembolism, we hypothesized that delayed thrombus resolution rather than abnormal coagulation is important, and that bacterial infection would be important for this misguidance.
  
  
  RESULTS
  Human CTEPH thromboemboli were harvested during pulmonary endarterectomy. The effects of Staphylococcal infection on thrombus organization were examined in a murine model of stagnant-flow venous thrombosis. Staphylococcal DNA, but not RNA, was detected in 6 of 7 thrombi from VA shunt carriers. In the mouse model, staphylococcal infection delayed thrombus resolution in parallel with upregulation of transforming growth factor (TGF) beta and connective tissue growth factor.
  
  
  CONCLUSIONS
  In the present work, we propose a mechanism of disease demonstrating that infection with Staphylococci enhances fibrotic vascular remodeling after thrombosis, resulting in misguided thrombus resolution. Thrombus infection appears to be a trigger in the evolution of CTEPH.
authors.affiliation: Department of Cardiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Diana
authors.initials: D
authors.lastname: Bonderman
authors.forename: Johannes
authors.initials: J
authors.lastname: Jakowitsch
authors.forename: Bassam
authors.initials: B
authors.lastname: Redwan
authors.forename: Helga
authors.initials: H
authors.lastname: Bergmeister
authors.forename: Maria-Klara
authors.initials: MK
authors.lastname: Renner
authors.forename: Heidi
authors.initials: H
authors.lastname: Panzenböck
authors.forename: Christopher
authors.initials: C
authors.lastname: Adlbrecht
authors.forename: Apostolos
authors.initials: A
authors.lastname: Georgopoulos
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.forename: Meinhard
authors.initials: M
authors.lastname: Kneussl
authors.forename: Irene M
authors.initials: IM
authors.lastname: Lang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001483:Base Sequence; D002557:Cerebrospinal Fluid Shunts / Q000009:adverse effects; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D017931:DNA Primers / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D006325:Heart Atria; D006801:Humans; D006849:Hydrocephalus / Q000601:surgery; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D017874:Immediate-Early Proteins / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010138:Pacemaker, Artificial / Q000009:adverse effects; D011655:Pulmonary Embolism / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D013203:Staphylococcal Infections / Q000150:complications*; D013210:Staphylococcus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D013211:Staphylococcus aureus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D014682:Vena Cava, Inferior; D020246:Venous Thrombosis / Q000209:etiology / Q000382:microbiology / Q000473:pathology
chemical_list: C526317:CCN2 protein, human; C526318:CCN2 protein, mouse; D017931:DNA Primers; D004269:DNA, Bacterial; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055513:Connective Tissue Growth Factor; D003094:Collagen