Vascular Disease Prevention (Discontinued) - Volume 5, Issue 1, 2008

In cultured human macrophages, apolipoprotein(a) (apo(a)), has pro-inflammatory properties attributable to the presence of oxidized phosphatidylcholine (ox-PC) in kringle V. In the plasma, apo(a) is linked to apoB100 and contains ox-PC, whereas in the artery plaque, the status of apo(a) is unknown. To this effect we have studied the properties of blood-derived apo(a) in the human carotid plaque. Subjects having either high or low plasma Lp(a) underwent carotid artery endarterectomy. After surgery, the plaques were frozen, laser dissected into macrophage dense and poor areas identified by CD68 reactivity and the sections extracted with 6 M GdHCl. Western blots of the extracts and immunoprecipitated apo(a) used anti-apo(a) specific polyclonal antibodies and T15, a monoclonal specific for ox-PC. The relationship of apo(a) to fibronectin was also studied. Apo(a) was only detected in the plaques of high plasma Lp(a) subjects, was partially fragmented and reacted with T15 indicating linkage to ox-PC. Moreover, ox-PC / apo(a) was present in macrophage-dense and macrophage-poor areas co-localized with fibronectin. In carotid artery plaques apo(a) colocalizes with fibronectin and probably other extraxcellular matrix elements, it is fragmented and linked to ox-PCs. We speculate that these modifications contribute to the pathogenicity of Lp(a) via apo(a).

Coronary revascularization procedures (coronary artery bypass graft - CABG surgery, percutaneous coronary intervention - PCI) are widely used in patients with coronary artery disease (CAD). By assessing myocardial perfusion, single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) aids the diagnosis of CAD and patient risk stratification, providing useful information regarding the decision about revascularization and is well suited to assess patients after intervention. Saphenous vein graft occlusion rates range between 8% (early) and 45% (11.5 years after CABG surgery), while the 10- year occlusion rate for arterial conduits such as the internal mammary artery is about 20%. PCI restenosis rates without stenting range between 20%-65% during the first 6 months of follow-up, while coronary stenting has been shown to reduce restenosis rates of about 20%. Chest pain and exercise electrocardiography are largely unhelpful in identifying patients at risk after revascularization procedures. MPI is of proven value to assess patients post intervention. Information gained from post-intervention myocardial SPECT is crucial to differentiate patients with angina from those with exo-cardiac chest pain syndromes, to assess peri-intervention myocardial damage/acute vessel closure, to predict-detect restenosis after PCI and graft occlusion/ stenosis after CABG surgery, to detect CAD progression in non-revascularized vessels, to assess left ventricular function (gated-SPECT), to evaluate the effects of intervention if required for occupational reasons and to predict longterm prognosis. With respect to detecting graft patency, MPI has an 80-96% sensitivity and 61-88% specificity, while regarding restenosis after PCI, sensitivity and specificity range between 74-94% and 67-88%, respectively.Despite the large amount of published data demonstrating the value of myocardial perfusion SPECT imaging in patients after CABG surgery or PCI, there is still debate on whether or not these tests should be performed routinely.

Background: The positive correlation between body mass index (BMI) and type 2 diabetes (DM) is well established. Data on the clinical resolution of DM through diet-induced weight loss, however, are limited. Objective: Examine the relationship between BMI reduction and resolution of type 2 DM using a medically-monitored, behavior modification, weight-management program involving low-calorie, meal replacement diets in obese subjects. Methods: Through a retrospective, chart review in a suburban weight management center, case patients (n=33) that clinically resolved DM were identified in a suburban weight loss clinic and compared with age- and gender-matched control patients (n= 100), that did not clinically resolve DM following the same interventions in the same weight loss clinic. Clinical resolution of DM was defined as an initial elevated glycohemoglobin (HbA1C) ≥ 6.0% that decreased to < 6.0% with weight loss allowing discontinuation of all diabetic medications. Results: The mean ± SD age was 54.1 ± 9.7 and 58.2 ± 9.4 years for cases and controls respectively, p = 0.03. The baseline BMI was similar for cases and controls, 42.0 ± 9.0 and 42.9 ± 8.6 kg/m2, p = 0.63. The absolute and relative reduction in BMI was 7.6 ± 3.7 kg/m2 and 18.1 ± 8.2% in cases vs. 3.9 ± 3.7 kg/m2 and 8.5 ± 8.0% in controls, respectively, (p < 0.0001 for both comparisons) over a mean duration of 11.2 ± 4.9 and 14.9 ± 13.0 months for cases and controls. Multiple logistic regression found that lower baseline HbA1C (p = 0.02), younger age (p = 0.01), and greater relative BMI reduction (p< 0.0001) were independent predictors of the clinical resolution of DM. Conclusions: Positive predictive factors for clinical resolution of DM through diet-induced weight loss include younger age and better baseline glycemic control. Clinical resolution of DM likely requires a minimum BMI reduction of 10% in obese individuals.

Atherosclerosis, a major vascular complication of type 2 diabetes mellitus (DM2), is a chronic inflammatory disease with increased glycoxidative stress in response to cellular and systemic glucose overload and lipid retention in the vessel wall. Glycoxidative modification of low density lipoprotein (LDL) is considered as a major causative factor of accelerated atherosclerosis in diabetic patients. Since atherogenesis starts before DM2 is diagnosed, this review will focus on the nature and extent of glycoxidative changes of LDL in subjects with impaired glucose tolerance (IGT). We review the evidence for the enhanced atherogenicity of LDL from IGT subjects including their contribution to the conversion of macrophages into a proatherogenic phenotype.

Erythropoietin (EPO) is a pleiotropic cytokine, which plays a neuroprotective role. Immune abnormalities have a close relationship with cerebral palsy (CP) development. Our aim was to investigate the roles of EPO and inflammatory cytokines in CP development. Serum samples of 31 CP patients (mean age 5.2 years, range 0 to 10 years), 37 neonates who suffered asphyxia and/or infection (mean age 6.3 days, range 0 to 19 days) and 40 controls (mean age 4.8 years, range 0 to 10 years) were obtained and kept at -40°C until assayed. EPO, tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6) levels were measured by an enzyme-linked immunosorbent assay double sandwich method (ABC-ELISA). The EPO levels in serum of neonatal patients were higher than in the control group or CP group. There was no difference between the CP group and control group with regard to serum EPO levels. The TNF-α and IL-6 levels in serum of CP and neonatal patients were higher than in the control group. The serum TNF-α levels of the CP group were higher than in neonatal patients. There was no difference between CP group and neonatal patients with regard to serum IL-6 levels. The “waterfall” immune inflammatory responses mediated by proinflammatory cytokines gain the upper hand in brain damage against the protective effect mediated by EPO. This may lead to CP through triggering the cascading effect of the immune-neuroendocrine network.

Saphenous vein (SV) is an excellent conduit for revascularization, especially for patients with multi-vessel coronary artery disease and peripheral arterial disease. However, its patency is limited in comparison with arterial grafts. Vein graft occlusion is the result of intimal hyperplasia and accelerated development of atherosclerosis, a cellular response triggered by surgical trauma, hypoxia, and increased wall stress. Nevertheless, the cellular mechanisms of vascular disease following bypass graft implantation, especially the impact of vein preparation and surgical techniques are less known than those that occur after angioplasty. The present article reviews the molecular mechanisms of vein graft remodeling, specifically thrombosis, alteration in endothelial function, modification of signaling pathways leading to cell proliferation and migration, role of intracellular calcium and activation of matrix metalloproteinases. The procedures of vein harvesting are discussed from the point of view of its possible impact on graft remodeling. Special attention is devoted to the consequences of pressure distention of the vein during the preparation for grafting; and an alternative preparation, which allows overcoming vasospasm without distention is discussed. The effects of pharmacological treatment during the preparation procedure and during arterialization are also discussed. An external support of the graft has been suggested to reduce graft remodeling, and its effects on the vascular mechanisms during arterialization are also considered. In conclusion, adjustment of the vein harvesting and preparation procedures combined with pharmacological treatment targeting the vasoconstrictor and proliferative mechanisms could improve long term vein graft patency.

Hypertension is considered as one of the major cardiovascular risk factors for the development of atherosclerosis, a chronic inflammatory disease of the arterial vasculature. Chronic activation of the renin angiotensin system (RAS) and enhanced oxidative stress are characteristic features of both, hypertension and atherosclerosis. In fact, Angiotensin II, the effector peptide of the RAS is a central mediator of vasoconstrictor and pro-inflammatory reactions in the cardiovascular system. Many of its effects are attributed to the formation of reactive oxygen species (ROS). Thus, angiotensin II via ROS may be a central link between hypertension and atherogenesis. In this review, we will summarize the current evidence proposing angiotensin II as a critical contributor to atherosclerotic plaque vulnerability via inflammation and hemodynamic alterations.

Retinal Vein Occlusion (RVO) is the most common visually disabling disease affecting the retina after diabetic retinopathy. Although the disease entity has long been known, its management is still controversial. Macular edema is the main reason for decreased visual acuity in RVO. Recently the vitreous cavity has increasingly been used as a reservoir of drugs for the direct treatment of macular edema through intravitreal injection. The most widely injected drugs so far are triamcinolone acetonide and bevacizumab. This review evaluates new medical and surgical treatment modalities aimed at reducing macular edema due to central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO), including intraocular injections of steroids and anti-vascular endothelial growth factor agents, vitrectomy, sheathotomy. Controversies and future treatment options are also considered.