The role of endothelial cell biology in endocarditis

Chorianopoulos, Emmanuel; Bea, Florian; Katus, Hugo A.; Frey, Nancy

doi:10.1007/s00441-008-0687-4

Cited by 25 publications

(25 citation statements)

References 109 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In vitro experiments show that recruited monocytes in valvular lesions contribute to the formation of vegetations by producing tissue factor and enhancing fibrin deposition [17]. Experimental models of IE using Staphylococcus epidermidis - or S. aureus -infected rabbits reveal the production of tissue factor by monocytes infiltrating vegetations [4], [18].…”

Section: Resultsmentioning

confidence: 99%

The Transcriptional Programme of Human Heart Valves Reveals the Natural History of Infective Endocarditis

Benoit¹,

Thuny

Priol

et al. 2010

PLoS ONE

View full text Add to dashboard Cite

Infective endocarditis (IE) is an infectious disease that is mainly caused by Staphylococcus aureus and Streptococcus sp. It usually leads to valvular destruction and vegetation formation. Its pathophysiology is badly understood and likely involves immune and coagulation systems with close interactions with the microorganism. Our objective was to evaluate host response by comparing transcriptional profiles of cardiac valves from IE patients with controls. Hierarchical clustering revealed a signature of IE consisting of 146 genes. Among the 89 up-regulated genes, we identified two genes strongly associated with IE: metalloproteinase 12 (MMP-12) and aquaporin-9, a member of the aquaglyceroporin membrane channel family. The up-regulation of MMP-12 gene is strengthened by the down-modulation of the gene encoding its inhibitor TIMP3. In addition, MMP-12 was expressed in macrophages infiltrating EI valves. We also found that aquaporin-9 was expressed in endothelial cells lining neo-vessel lumen, suggesting that aquaporin-9 might be associated with neovascularization of infected valves leading to tissue oedema secondary to the inflammatory process. The Gene Ontology annotation and the resulting functional classification showed that most up-regulated genes account for recruitment of inflammatory cells in vegetations, angiogenesis and remodelling of endocardium tissue. A network analysis confirmed the involvement of molecules related to the remodelling of endocardium tissue and angiogenesis in IE. It also evidenced the role of caspases, especially that of caspase-9 and intrinsic apoptotic pathway in IE. Based on this study we propose a scenario for the natural history of IE in humans. Some parameters identified in this work could become tools for measuring the disease activity and should be tested as biomarkers for diagnosis or prognosis assessment in future studies.

show abstract

Section: Resultsmentioning

confidence: 99%

The Transcriptional Programme of Human Heart Valves Reveals the Natural History of Infective Endocarditis

Benoit¹,

Thuny

Priol

et al. 2010

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Activation and invasion of the vascular endothelium is thought to underlie the main symptoms of S. aureus sepsis (Kerrigan and McDonnell, 2015). Furthermore, S. aureus has a propensity to invade the endothelial lining of heart valves leading to valve colonization and bacterial endocarditis (Chorianopoulos et al, 2009). Animal models have revealed that intravascular S. aureus preferentially attaches to the endothelium of postcapillary venules (Laschke et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Staphylococcus aureus recruits Cdc42GAP through recycling endosomes and the exocyst to invade human endothelial cells

Rauch

Hennings

Trasak

et al. 2016

Journal of Cell Science

View full text Add to dashboard Cite

Activation and invasion of the vascular endothelium by Staphylococcus aureus is a major cause of sepsis and endocarditis. For endothelial cell invasion, S. aureus triggers actin polymerization through Cdc42, N-WASp (also known as WASL) and the Arp2/3 complex to assemble a phagocytic cup-like structure. Here, we show that after stimulating actin polymerization staphylococci recruit Cdc42GAP (also known as ARHGAP1) which deactivates Cdc42 and terminates actin polymerization in the phagocytic cups. Cdc42GAP is delivered to the invading bacteria on recycling endocytic vesicles in concert with the exocyst complex. When Cdc42GAP recruitment by staphylococci was prevented by blocking recycling endocytic vesicles or the exocyst complex, or when Cdc42 was constitutively activated, phagocytic cup closure was impaired and endothelial cell invasion was inhibited. Thus, to complete invasion of the endothelium, staphylococci reorient recycling endocytic vesicles to recruit Cdc42GAP, which terminates Cdc42-induced actin polymerization in phagocytic cups. Analogous mechanisms might govern other Cdc42-dependent cell functions.

show abstract

“…Indeed, S. aureus is a leading cause of sepsis and infective endocarditis [1], [6]–[8]. Colonization of the heart and subsequent formation of vegetations involves a number of complex interactions [9]–[11]. Animal studies have shown that staphylococcal fibronectin-binding protein A (FnBPA) is able to support the colonization of heart valves by otherwise non-pathogenic Lactococcus lactis , as well as promote dissemination into the spleen [12], [13].…”

Section: Introductionmentioning

confidence: 99%

Staphylococcus aureus Host Cell Invasion and Virulence in Sepsis Is Facilitated by the Multiple Repeats within FnBPA

et al. 2010

View full text Add to dashboard Cite

Entry of Staphylococcus aureus into the bloodstream can lead to metastatic abscess formation and infective endocarditis. Crucial to the development of both these conditions is the interaction of S. aureus with endothelial cells. In vivo and in vitro studies have shown that the staphylococcal invasin FnBPA triggers bacterial invasion of endothelial cells via a process that involves fibronectin (Fn) bridging to α5β1 integrins. The Fn-binding region of FnBPA usually contains 11 non-identical repeats (FnBRs) with differing affinities for Fn, which facilitate the binding of multiple Fn molecules and may promote integrin clustering. We thus hypothesized that multiple repeats are necessary to trigger the invasion of endothelial cells by S. aureus. To test this we constructed variants of fnbA containing various combinations of FnBRs. In vitro assays revealed that endothelial cell invasion can be facilitated by a single high-affinity, but not low-affinity FnBR. Studies using a nisin-inducible system that controlled surface expression of FnBPA revealed that variants encoding fewer FnBRs required higher levels of surface expression to mediate invasion. High expression levels of FnBPA bearing a single low affinity FnBR bound Fn but did not invade, suggesting that FnBPA affinity for Fn is crucial for triggering internalization. In addition, multiple FnBRs increased the speed of internalization, as did higher expression levels of FnBPA, without altering the uptake mechanism. The relevance of these findings to pathogenesis was demonstrated using a murine sepsis model, which showed that multiple FnBRs were required for virulence. In conclusion, multiple FnBRs within FnBPA facilitate efficient Fn adhesion, trigger rapid bacterial uptake and are required for pathogenesis.

show abstract

The role of endothelial cell biology in endocarditis

Cited by 25 publications

References 109 publications

The Transcriptional Programme of Human Heart Valves Reveals the Natural History of Infective Endocarditis

The Transcriptional Programme of Human Heart Valves Reveals the Natural History of Infective Endocarditis

Staphylococcus aureus recruits Cdc42GAP through recycling endosomes and the exocyst to invade human endothelial cells

Staphylococcus aureus Host Cell Invasion and Virulence in Sepsis Is Facilitated by the Multiple Repeats within FnBPA

Contact Info

Product

Resources

About