Malondialdehyde-Acetaldehyde Modified (MAA) Proteins Differentially Effect the Inflammatory Response in Macrophage, Endothelial Cells and Animal Models of Cardiovascular Disease.

Chronic inflammation plays a critical role in the pathogenesis of atherosclerosis. Currently, the mechanism(s) by which inflammation contributes to this disease are not entirely understood. Inflammation is known to induce oxidative stress, which can lead to lipid peroxidation. Lipid peroxidation can result in the production of reactive by-products that can oxidatively modify macromolecules including DNA, proteins, and lipoproteins. A major reactive by-product of lipid peroxidation is malondialdehyde (MDA). MDA can subsequently break down to form acetaldehyde (AA). These two aldehydes can covalently interact with the epsilon (ε)-amino group of lysines within proteins and lipoproteins leading to the formation of extremely stable, highly immunogenic malondialdehyde/acetaldehyde adducts (MAA-adducts). The aim of this study was to investigate the inflammatory response to MAA-modified human serum albumin (HSA-MAA) and low-density lipoprotein (LDL-MAA). We found that animals injected with LDL-MAA generate antibodies specific to MAA-adducts. The level of anti-MAA antibodies were further increased in an animal model of atherosclerosis fed a Western diet. An animal model that combined both high fat diet and immunization of MAA-modified protein resulted in a dramatic increase in antibodies to MAA-adducts and vascular fat accumulation compared with controls. In vitro exposure of endothelial cells and macrophages to MAA-modified proteins resulted in increased fat accumulation as well as increased expression of adhesion molecules and pro-inflammatory cytokines. The expression of cytokines varied between the different cell lines and was unique to the individual modified proteins. The results of these studies demonstrate that different MAA-modified proteins elicit unique responses in different cell types. Additionally, the presence of MAA-modified proteins appears to modulate cellular metabolism leading to increased accumulation of triglycerides and further progression of the inflammatory response.

IL-1ß (Interleukin-1ß) and TNF-α (Tumor Necrosis Factor-α) Impact Abdominal Aortic Aneurysm Formation by Differential Effects on Macrophage Polarization.

OBJECTIVE: Abdominal aortic aneurysms are inflammatory in nature and are associated with some risk factors that also lead to atherosclerotic occlusive disease, most notably smoking. The purpose of our study was to identify differential cytokine expression in patients with abdominal aortic aneurysm and those with atherosclerotic occlusive disease. Based on this analysis, we further explored and compared the mechanism of action of IL (interleukin)-1ß versus TNF-α (tumor necrosis factor-α) in abdominal aortic aneurysm formation. APPROACH AND RESULTS: IL-1ß was differentially expressed in human plasma with lower levels detected in patients with abdominal aortic aneurysm compared with matched atherosclerotic controls. We further explored its mechanism of action using a murine model and cell culture. Genetic deletion of IL-1ß and IL-1R did not inhibit aneurysm formation or decrease MMP (matrix metalloproteinase) expression. The effects of IL-1ß deletion on M1 macrophage polarization were compared with another proinflammatory cytokine, TNF-α. Bone marrow-derived macrophages from IL-1ß-/- and TNF-α-/- mice were polarized to an M1 phenotype. TNF-α deletion, but not IL-1ß deletion, inhibited M1 macrophage polarization. Infusion of M1 polarized TNF-α-/- macrophages inhibited aortic diameter growth; no inhibitory effect was seen in mice infused with M1 polarized IL-1ß-/- macrophages. CONCLUSIONS: Although IL-1ß is a proinflammatory cytokine, its effects on aneurysm formation and macrophage polarization differ from TNF-α. The differential effects of IL-1ß and TNF-α inhibition are related to M1/M2 macrophage polarization and this may account for the differences in clinical efficacy of IL-1ß and TNF-α antibody therapies in management of inflammatory diseases.

Intravascular ultrasound to aid in the diagnosis and revision of an intra-aortic pedicle screw: illustrative case.

BACKGROUND: Pedicle screw impingement on vessel walls has the potential for complications due to pulsatile effects and wall erosion. Artifacts from spinal instrumentation create difficulty in accurately evaluating this interface. The authors present the first case of intravascular ultrasound (IVUS) used to characterize a pedicle screw breach into the aortic lumen. OBSERVATIONS: A 21-year-old female with surgically corrected scoliosis underwent computed tomography angiography (CTA) 3 years postoperatively, which revealed a pedicle screw within the thoracic aorta lumen. Metal artifact distorted the CTA images, which prompted the decision to use intraoperative IVUS. The IVUS confirmed the noninvasive imaging findings and guided final decisions regarding aortic endograft size and location during spine hardware revision. LESSONS: For asymptomatic patients presenting with pedicle screws malpositioned in or near the aorta, treatment decisions revolve around the extent of vessel wall penetration. Intraluminal depth can be obscured by artifact on computed tomography or magnetic resonance imaging or inadequately evaluated by a transesophageal echocardiogram. In our intraoperative experience, IVUS confirmed the depth of vessel lumen violation by a single pedicle screw and no wall penetration by two additional screws of concern. This was useful in deciding on thoracic endovascular aortic repair graft size and landing zone and facilitated safe spinal instrumentation removal and revision.

Erroneous Central Venous Catheter Placement: Multidisciplinary Primary Surgical Repair of the Vertebral Artery.

Central venous catheters are a common practice in critical care medicine. These lines are of particular importance when a patient needs large volume resuscitation or medications that cannot be infused through a peripheral line. Even though central venous catheters are frequently utilized, they are associated with potentially significant risks that one must be aware of when attempting placement. The anatomy and pertinent complications are key for any healthcare professional to be aware of during this procedure. As such, vascular injury has been described in the literature, but vertebral artery injury and common repair techniques are less common. Primary repair of the second vertebral artery segment is infrequently detailed in the literature and this report describes pertinent case details and plan of action for identification and repair of iatrogenic vertebral artery injury following catheter placement.