Role for staphylococci in misguided thrombus resolution of chronic thromboembolic pulmonary hypertension.
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.
Bonderman
Diana
D
Department of Cardiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Jakowitsch
Johannes
J
Redwan
Bassam
B
Bergmeister
Helga
H
Renner
Maria-Klara
MK
Panzenböck
Heidi
H
Adlbrecht
Christopher
C
Georgopoulos
Apostolos
A
Klepetko
Walter
W
Kneussl
Meinhard
M
Lang
Irene M
IM
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
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