Correlation Between Serum Markers of Unstable Plaque and Virtual Histology of Unstable Plaque Visualized by IVUS

Overview

Thirty patients scheduled to coronary angiography and IVUS in according to their treating physician decision will be enrolled in the study. The coronary angiography and IVUS will be done on according to regular clinical standards. As the study protocol, 40 cc of blood will be drawn from the patients after written informed consent. The laboratory tests will be processed for the above mentioned serum markers of unstable plaque. A multivariate correlation test will be done between the different serum markers and the plaque morphology by angiography and composition (virtual histology) by IVUS.

Serum markers of unstable plaque Myeloperoxidase is a lysosomal enzyme, requiring heme as a cofactor, released from neutrophilic granules, monocytes, and some subtypes of tissue macrophages. Myeloperoxidase is also linked to oxidation of lipids in low-density lipoproteins (LDL), dysfunctional high density lipoproteins (HDL), and consumption of nitric oxide thereby rendering the normally anti-thrombotic endothelial surface thrombogenic via the expression of various pro-thrombotic and anti-fibrinolytic factor (19). Myeloperoxidase plays a role in the degradation of the fibrous cap, making it both a marker of inflammation and one of plaque instability. Interest in MPO intensified after a report by Brennan and colleagues (20) indicated that a single initial measurement of plasma myeloperoxidase independently predicts the early risk of myocardial infraction, as well as the risk of major adverse cardiac events in the ensuring 30-day and 6-month periods. Two markers of recent interest relating to plaque vulnerability pregnancy-associated protein A(PAPP-A) and placenta growth factor (P1GF). Pregnancy -associated protein A is a metalloproteinase, initially identified in the sera of pregnant women (21). A large study has illustrated that decreases in IGF-1 appear to be cardio protective, yet some research shows that increases in PAPP-A, which should also increase the bioavailability of IGF-1, may be a relevant marker for the presence and extent of coronary atherosclerosis (22). It is believed that PAPP-A is released during plaque destabilization and appears to be a valuable indicator of unstable angina and acute MI in patients lacking other indicators of necrosis (23). Placenta growth factor, is a member of the vascular endothelial growth factor family, which stimulates vascular smooth muscle growth, recruits macrophages into atherosclerotic lesion, up-regulates production of tumor necrosis factor- and monocyte chemotactic protein 1 by macrophages, and stimulates pathological angiogenesis (24). It appears to be an initiator of the inflammatory process. In one study, elevated P1GF levels not only identified patients with acute chest pain who developed ACS, but also those patients with an increased risk of recurrent instability after hospital discharge (25). Plasma elevation of CRP have been reported fraction, and are acute ischemia and myocardial in fraction, and are predictive of the risk of recurrent ischemia among hospitalization patients with unstable angina (26). Matrix metalloproteinases. MMPs are a diverse family of powerful, zinc-containing enzymes expressed by macrophage- derived foam cells, SMCs and other vascular cells within atherosclerotic lesions (27) .It has been previously demonstrated that MMPs are responsible for remodeling of the ECM during all stages of atheromatous development and may directly contribute to fibrous cap weakening and plaque rupture within disease arteries (28). CD40 ligand (CD40L) is an immunoregulatory transmembrane protein that belongs to the tumor necrosis factor (TNF) super family. It is expressed on the surface of many cells types, including leukocytes, ECs, SMSs, macrophages, and activated platelets (29). Ligand receptor binding on these cells triggers the expression and secretion of a variety of pro-inflammatory and procoagulant mediators, including CAMs, cytokines, chemokines, growth factors, MMPs, and TF (29). Recent data suggest that CD40L plays a central role in the inflammatory process that contributes to plaque destabilization in CAD (30), and elevation in soluble, biologically active CD40L (Scd40l) have been demonstrated in the serum of ACS patients (31). Paraoxonase and atherogenic HDL The enzyme PON1 is known to be tightly bound with HDL in serum, and several studies suggest that it is this association that contributes to the protection conferred by HDL against LDL oxidation (33-36). The aim of the study is to find a correlation between serum markers of unstable plaque and virtual histology of unstable plaque visualized by IVUS. Patients and methods: Thirty patients scheduled to coronary angiography and IVUS in according to their treating physician decision will be enrolled in the study. The coronary angiography and IVUS will be done on according to regular clinical standards. As the study protocol, 40 cc of blood will be drawn from the patients after written informed consent. The laboratory tests will be processed for the above mentioned serum markers of unstable plaque. A multivariate correlation test will be done between the different serum markers and the plaque morphology by angiography and composition (virtual histology) by IVUS.