Inflammation: a denominating factor in coronary artery disease and venous bypass graft failure

Niessen, J.W.M. [Promotor]Hinsbergh, V.W.M. van [Promotor]Stooker, W. [Copromotor]Eijsman, L. [Copromotor

C4b-Binding Protein Is Present in Affected Areas of Myocardial Infarction during the Acute Inflammatory Phase and Covers a Larger Area than C3

BACKGROUND: During myocardial infarction reduced blood flow in the heart muscle results in cell death. These dying/dead cells have been reported to bind several plasma proteins such as IgM and C-reactive protein (CRP). In the present study we investigated whether fluid-phase complement inhibitor C4b-binding protein (C4BP) would also bind to the infarcted heart tissue. METHODS AND FINDINGS: Initial studies using immunohistochemistry on tissue arrays for several cardiovascular disorders indicated that C4BP can be found in heart tissue in several cardiac diseases but that it is most abundantly found in acute myocardial infarction (AMI). This condition was studied in more detail by analyzing the time window and extent of C4BP positivity. The binding of C4BP correlates to the same locations as C3b, a marker known to correlate to the patterns of IgM and CRP staining. Based on criteria that describe the time after infarction we were able to pinpoint that C4BP binding is a relatively early marker of tissue damage in myocardial infarction with a peak of binding between 12 hours and 5 days subsequent to AMI, the phase in which infiltration of neutrophilic granulocytes in the heart is the most extensive. CONCLUSIONS: C4BP, an important fluid-phase inhibitor of the classical and lectin pathway of complement activation binds to jeopardized cardiomyocytes early after AMI and co-localizes to other well known markers such as C3b

Development of New Constructions Against Washing the Reservoirs Abrasive Shores

დამუშავებულია წყალსაცავების აბრაზიული ნაპირების წარეცხვისაგან დამცავი ახალი კონსტრუქციები – „ჰექსაბლოკი“ და „ტეტრაბლოკი“, რომლებიც გამოირჩევა ფერდზე მაღალი ტალღაჩამქრობი ეფექტით, არსებულთან შედარებით მისი დამზადება ეკონომიურია, ხასიათდება მაღალი გამჭოლიანობით, წახნაგების ხარჯზე ერთმანეთთან დიდი შეჭიდულობით, ნაკლები წონით და ნაპირის ფერდზე მდგრადობით. შემოთავაზებული უნივერსალური ფორმულის გამოყენებით, ჰექსაბლოკის და ტეტრაბლოკის ფერდებზე წონასწორობა გამოითვლება მინიმალური დასაშვები წონის გათვალისწინებით.new constructions against washing the reservoirs abrasive shores are being developed – Hexablock and Tetrablock, which are distinguished by the high ripple effect on the slope, their production are more economical compared to the existing one, they are characterized by high piercing, by great traction at the expense of facets, by less weight and stability on the shore of slope. Using the proposed universal formula, the equilibrium of Hexablock and Tetrablock on the slopes is calculated by taking into account the minimum permissible weight

Increased infiltration of Chlamydophila pneumoniae in the vessel wall of human veins after perfusion

Background: Several studies have suggested an association between Chlamydophila pneumoniae (Cp) infection and atherosclerosis. A recent study detected Cp DNA in the saphenous vein of 12% of all patients before bypass grafting and in 38% of failed grafts. We used a system in which human veins were perfused with autologous blood under arterial pressure. Materials and methods: Veins were surplus segments of saphenous veins of coronary artery bypass grafting (CABG) patients. Vein grafts were perfused with the blood of the same patient after CABG procedures. Veins were analysed for Cp-specific membrane protein using immunohistochemical and PCR analysis. Veins were analysed before and after perfusion (up to 4 h). The number of Cp positive cells was then quantified in the vein layers. Results: Cp protein was detected within macrophages only. In non-perfused veins, Cp was present in the adventitia in 91% of all patients, in the circular (64%) and longitudinal (23%) layer of the media. No positivity was found in the intima. Perfusion subsequently resulted in a significant increase of Cp positive cells within the circular layer of the media that, however, differed strongly between different patients. Cp DNA was not detected by PCR in those specimens. Conclusion: Cp protein was present in 91% of veins, but the number of positive cells differed remarkably between patients. Perfusion of veins resulted in increased infiltration of Cp into the circular layer. These results may point to a putative discriminating role of Cp with respect to graft failure between different patients. © 2008 The Authors

PX-18 Protects Human Saphenous Vein Endothelial Cells under Arterial Blood Pressure

Vascular Surger

C1-esterase inhibitor protects against early vein graft Remodelling under arterial blood pressure

Vascular Surger

Activated complement is more extensively present in diseased aortic valves than naturally occurring complement inhibitors: a sign of ongoing inflammation

Recent studies indicate a role for complement in the pathogenesis of aortic valve disease. However, the role of naturally occurring anti-complement mediators in this context is unknown. In this study, we have analysed this in three different pathological conditions of the aortic valve: degeneration, atherosclerosis and bacterial endocarditis. Human aortic valves were obtained at autopsy (n = 30): 5 control valves, 10 aortic valves with atherosclerotic changes, 10 aortic valves with degenerative changes and 5 degenerative changed aortic valves with bacterial infection. These valves were analysed immunohistochemically for the presence of activated complement (C3d and C5b9) and the complement inhibitors C1-inh and clusterin. Areas of positivity were then quantified. C3d, C5b9 and the complement inhibitors C1-inh and clusterin depositions were mainly found in the endothelium and extracellular matrix in aortic valves. All these mediators were already present in control valves, but the area of positivity increased significantly in response to the different diseases, with the highest increase in response to bacterial endocarditis. Interestingly, in all three aortic diseases, the depositions of complement were significantly more widespread than that of their inhibitors. Our study indicates that anti-complement mediators (C1-inh and clusterin) are deposited in diseased aortic valves together with activated complement, indicating an existing counter response against complement locally in the valve. However, deposition of activated complement is significantly more widespread than that of its inhibitors, which could explain ongoing inflammation in those diseased aortic valve

N(epsilon)-(carboxymethyl)lysine depositions in intramyocardial blood vessels in human and rat acute myocardial infarction: a predictor or reflection of infarction?

Advanced glycation end products (AGEs), such as N(epsilon)-(carboxymethyl)lysine (CML), are implicated in vascular disease. We previously reported increased CML accumulation in small intramyocardial blood vessels in diabetes patients. Diabetes patients have an increased risk for acute myocardial infarction (AMI). Here, we examined a putative relationship between CML and AMI. Heart tissue was stained for CML, myeloperoxidase, and E-selectin in AMI patients (n=26), myocarditis patients (n=17), and control patients (n=15). In AMI patients, CML depositions were 3-fold increased compared with controls in the small intramyocardial blood vessels and predominantly colocalized with activated endothelium (E-selectin-positive) both in infarction and noninfarction areas. A trend of increased CML positivity of the intima of epicardial coronary arteries did not reach significance in AMI patients. In the rat heart AMI model, CML depositions were undetectable after 24 hours of reperfusion, but became clearly visible after 5 days of reperfusion. In line with an inflammatory contribution, human myocarditis was also accompanied by accumulation of CML on the endothelium of intramyocardial blood vessels. CML, present predominantly on activated endothelium in small intramyocardial blood vessels in patients with AMI, might reflect an increased risk for AMI rather than being a result of AM