C3H apoE(-/-) mice have less atherosclerosis than C57BL apoE(-/-) mice despite having a more atherogenic serum lipid profile

Wild-type C57BL mice are known to be susceptible to diet-induced atherosclerosis, whilst C3H mice are resistant. We investigated the effect of these background strains on the hyperlipidaemia and atherosclerosis that develops in mice deficient in apolipoprotein E (apoE(-/-)). Male and female apoE(-/-) mice on C3H/HeNHsd (C3H) and C57BL/6J (C57) backgrounds were fed atherogenic Western diet for 12 weeks. Serum cholesterol and triglyceride concentrations were measured and atherosclerosis quantified in the aortic sinus. C3H apoE(-/-) mice fed normal diet had 1.5 2 fold higher serum cholesterol levels than C57 apoE(-/-) mice and 4-5 fold higher serum triglyceride concentrations. Feeding Western diet caused a 4-5 fold increase in serum cholesterol in all mice, but levels of triglyceride were either attenuated or were unaffected in C3H apoE(-/-) and C57 apoE(-/-) mice, respectively. C3H apoE(-/-) mice had approximately 2 fold higher serum cholesterol and 4 fold higher triglyceride concentrations than the C57 apoE(-/-) mice throughout the study. Serum triglyceride concentrations were 35-108% higher in male C3H apoE(-/-) than female C3H apoE(-/-) mice. Most of the lipids were present in the very low density lipoprotein (VLDL)/chylomicron fraction in both strains of mice whether they were fed normal or Western diet. Notwithstanding the lower plasma lipid concentrations, atherosclerotic lesion areas were more than 2-fold larger in C57 apoE(-/-) than in C3H apoE(-/-) mice (males 68 +/- 11 x 10(3) vs 30 +/- 6 x 10(3) females 102 +/- 12 x 10(3) vs 41 +/- 8 x 10(3) microm2. mean +/- SEM).     

Compensatory enlargement and stenosis develop in apoE(-/-) and apoE*3-Leiden transgenic mice

Atherosclerotic mouse models develop little ischemic organ damage and no infarctions, despite the presence of large atherosclerotic lesions. Therefore, we hypothesize that luminal changes do not follow atherosclerotic lesion development. Because a phenomenon that may explain the discrepancy between luminal changes and lesion size is vascular remodeling, we measured parameters of vascular remodeling in the carotid arteries (CAs), thoracic aorta (TA), and abdominal aorta (AA) of apolipoprotein E (apoE)-deficient (apoE(-/-)) and apoE*3-Leiden mice, 2 well-known mouse models of atherosclerosis. Atherosclerotic lesions were classified (American Heart Association [AHA] types II through V), and plaque thickness, compensatory enlargement versus constrictive remodeling, lumen diameter, stenosis, and media thickness were measured relative to the nondiseased arterial wall. In CAs, plaque thickness increased during atherogenesis. CAs showed compensatory enlargement (apoE(-/-) 55%, apoE*3-Leiden 38%). Regression analysis revealed a positive correlation between plaque and lumen area (for apoE(-/-), R=0.95; for apoE*3-Leiden, R=0.90). Medial thinning and elastolysis were also observed. During atherogenesis, lumen diameter decreased (apoE(-/-) -69%, apoE*3-Leiden -40%), and stenosis >70% developed. TA and AA showed similar features, but neither developed a progressive decrease in lumen diameter or stenosis >70%. In CAs, TA, and AA of apoE(-/-) and apoE*3-Leiden mice, atherogenesis is associated with compensatory enlargement, medial thinning, and elastolysis. A progressive decrease in lumen diameter and stenoses >70% occur only in CAs. Vascular remodeling is more prominent in apoE(-/-) mice.     

Pancreatic exocrine insufficiency in LXRbeta-/- mice is associated with a reduction in aquaporin-1 expression

Liver X receptors (LXRs) α and β are nuclear oxysterol receptors with a key role in cholesterol, triglyceride, and glucose metabolism. In LXRβ^−/− mice on a normal diet, there is a reduction in size of perigonadal fat pad and, on high-fat diet there is resistance to obesity. In the present study, we investigated the reason for the resistance of LXRβ^−/− mice to weight gain. In LXRβ^−/− mice we found pancreatic exocrine insufficiency with reduced serum levels of amylase and lipase, reduced proteolytic activity in feces, chronic inflammatory infiltration, and, in the ductal epithelium, an increased apoptosis without compensatory proliferation. Electron microscopy revealed ductal dilatation with intraductal laminar structures characteristic of cystic fibrosis. To investigate the relationship between LXRβ and pancreatic secretion, we studied the expression of LXRβ and the water channel, aquaporin-1 (AQP1), in the ductal epithelium of the pancreas. In WT mice, ductal epithelial cells expressed LXRβ in the nuclei and AQP1 on the plasma membrane. In LXRβ^−/− mice neither LXRβ nor AQP1 was detectable. Moreover, in WT mice the LXR agonist (T2320) increased AQP1 gene expression. These data demonstrate that in LXRβ^−/− mice dietary resistance to weight gain is caused by pancreatic insufficiency and that LXRβ regulates pancreatic exocrine secretion through the control of AQP1 expression. Pancreatic exocrine insufficiency is the main cause of malabsorption syndrome responsible for weight loss in adults and growth failure in children. Several genes are known to be involved in the pathogenesis and susceptibility to pancreatic insufficiency. LXRβ should be included in that list.     

Low carbohydrate, high protein diet promotes atherosclerosis in apolipoprotein E/low-density lipoprotein receptor double knockout mice (apoE/LDLR(-/-))

Although in apoE/LDLR(-/-) mice atherosclerotic plaques develop spontaneously, various atherogenic diets (e.g. Western diet) are frequently used to accelerate the disease in this model. The objective of this study was to compare the effects on atherosclerosis of Western diet and other types of high-fat, high cholesterol, hypertriglyceridemic diets with the effects of the low carbohydrate, high protein (LCHP) diet. 16-18 week old mice with pre-established atherosclerosis were assigned to experimental groups and fed for the next 10 weeks with control diet, margarine diet (margarine 7%), hypertrigliceridemic diet (fructose 62%), high-fat diet (Western diet), high cholesterol diet (egg yolk diet) or with LCHP diet. No differences in body weight were observed among experimental groups. Plasma cholesterol concentration was significantly increased in egg yolk diet- and LCHP diet-fed apoE/LDLR(-/-) mice as compared to other types of diets. Plasma concentration of triacylglycerols was significantly elevated in egg yolk diet- and LCHP diet-fed apoE/LDLR(-/-) mice. The area of atherosclerotic plaques in the aortic root was substantially increased in LCHP diet-fed mice as compared to other types of diets. Furthermore, in brachiocephalic arteries of LCHP diet-fed mice there was evidence of plaque rupture. In conclusion, the LCHP diet promoted atherosclerosis in apoE/LDLR(-/-) mice more intensively than classical Western diet and favored the development of unstable lesions.     

Down-regulation of endothelial adhesion molecules and leukocyte adhesion by treatment with superoxide dismutase is beneficial in chronic immune experimental colitis

Modulation of adhesion molecule expression that govern trafficking of leukocytes into the inflamed intestine is envisioned as a new strategy for treatment of inflammatory bowel disease (IBD). This study was designed to determine the impact of reducing oxidative stress on adhesion molecules expression and leukocyte recruitment in experimental chronic colitis. For that purpose, colitic interleukin-10 knockout and wild-type mice were studied. Groups of animals were treated with Cu/Zn superoxide dismutase (SOD1) 13 mg/kg/d or vehicle for either 7 or 14 days. Expression of vascular cell adhesion molecule-1 and mucosal addressin cell adhesion molecule-1 were determined; leukocyte-endothelial cell interactions in colonic venules were studied with intravital microscopy; and changes in colon pathology and biomarkers of colitis severity were determined. Development of colitis was associated with a marked increase in endothelial vascular cell adhesion molecule-1 and mucosal addressin cell adhesion molecule-1 expression, which were significantly reduced by treatment with SOD1. The increase in leukocyte rolling and adhesion in colonic venules of colitic mice were significantly reduced by administration of SOD1. This treatment markedly reduced colonic lipid hydroperoxidation, myeoloperoxidase activity, and plasma levels of serum amyloid A protein and resulted in significant, although modest, reductions in histologic damage score. The therapeutic value of SOD1 when administered prophylactically was assessed in the dextran sulfate sodium model of colitis with similar positive results. These results indicate that SOD1 affords significant amelioration of colonic inflammatory changes in experimental colitis. Down-regulation of adhesion molecule expression, reduction of lipid hydroperoxidation, and recruitment of leukocytes into the inflamed intestine contribute to this beneficial effect.     

Lipoprotein (a) is associated with endothelial function in healthy postmenopausal women

BACKGROUND: Lipoprotein (a) (Lp(a)) is an independent risk factor for atherosclerotic cardiovascular disease. The atherogenic potential of Lp(a) may be by impairment of endothelial function. Objectives. We investigated the relation of Lp(a) plasma levels to endothelium dependent and independent dilatation of the brachial artery in healthy postmenopausal women. METHODS: One hundred and five healthy postmenopausal women aged 52-67 years were included in the study. Endothelial function was assessed non-invasively by measuring percent lumen diameter change in the brachial artery after reactive hyperemia and sublingual nitroglycerine spray. RESULTS: Flow mediated dilatation was inversely related to the plasma logLp(a) level. Mean change per unit logLp(a) increase:-2.83% (95% CI: -5.22--0.43). Elevated Lp(a) (>239 mg/l) (upper quartile) was associated with an impaired flow mediated vasodilatation (2.4%+/-1. 2) compared to Lp(a) < or =239 mg/l (5.2%+/-0.7). Adjustment for other cardiovascular risk factors did not change the magnitude of the association. Nitroglycerine-induced vasodilatation was not significantly lower in the high Lp(a) level group, compared to the group with normal levels of Lp(a) (< or =239 mg/l) (8.0+/-1.2 vs. 11.4%+/-0.8). CONCLUSION: Elevated lipoprotein (a) levels are associated with an impaired endothelial function in healthy postmenopausal women, independent of conventional risk factors for cardiovascular disease. Since Lp(a) may be pathogenetically important for early vascular damage, elevated Lp(a) levels might contribute to the increased cardiovascular risk seen in postmenopausal women.     

Low expression of lymphocyte function-associated antigen (LFA)-1 and LFA-3 adhesion molecules is a common trait in Burkitt's lymphoma associated with and not associated with Epstein-Barr virus.

Lymphocyte function-associated antigens 1 and 3 (LFA-1, LFA-3) and intercellular adhesion molecule 1 (ICAM-1) are cell surface adhesion molecules necessary for immune processes requiring intercellular contact. It was recently proposed that malignant Burkitt's lymphoma cells (BL) may escape from immunosurveillance through the downregulation of LFA-1 (CD11a/CD18) or LFA-3 (CD58) and ICAM-1 (CD54) molecules. Expression of these three adhesion antigens was investigated in 19 BL lines. LFA-1 or LFA-3 expression was found to be absent or low in 8 of 11 Epstein-Barr virus (EBV) genome positive BL, but strongly expressed on all nonmalignant EBV genome positive lymphoblastoid cell lines (LCL). Negative or weak expression of LFA-1 and LFA-3 was also observed in 7 of 8 EBV genome negative BL. ICAM-1 was found to be expressed on the cell surface of the majority of BL lines. BL lines growing as individual cells did not express LFA-1, whereas clump-forming BL lines expressed this marker involved in B-cell homotypic aggregation. Expression of LFA-1 and LFA-3 was induced on in vitro infection of EBV-negative BL cells with the immortalizing EBV strain B95-8, and weakly with the nonimmortalizing EBV strain P3HR1. EBNA2 and LMP, two EBV encoded proteins expressed in LCL and in BL infected with B95-8 (BL/B95-8), are not expressed in P3HR1 infected BL cells (BL/P3HR1). Stable expression of EBNA2 after gene transfer in a BL/P3HR1 cell line did not restore the level of LFA-1 and LFA-3 found on BL/B95-8 cells. In EBV-positive BL cells expressing LFA-1 and LFA-3, LMP was found coexpressed, supporting the recent finding of the role of LMP in B-cell adhesion receptor activation. Consequently, diminished LFA-1 and LFA-3 expression appears to be a common characteristic of numerous EBV-positive BL as well as EBV-negative BL. These findings are discussed in the framework of BL pathogenesis.     

Pancreatic acinar cell dysfunction in CFTR(-/-) mice is associated with impairments in luminal pH and endocytosis

BACKGROUND & AIMS: We have previously shown that endocytosis at the apical plasma membrane in pancreatic acinar cells is coupled to ductal bicarbonate secretion into the lumen. We hypothesized that decreased bicarbonate secretion in cystic fibrosis (CF) inhibits apical endocytosis. The aim of this study was to determine in cftr(-/-) mice (1) if the pH of the pancreatic juice is acidic compared with wild-type (WT) controls, (2) if there is a selective block in endocytosis, and (3) if alkalinization of the luminal fluid reverses this defect. METHODS: Fluid secretion and pH of pancreatic juice were measured. Exocytosis, endocytosis, and morphology were compared in pancreatic lobules from cftr(-/-) and WT mice. RESULTS: Pancreatic juice pH was 8.12 +/- 0.06 in WT mice compared with 6.60 +/- 0.04 in cftr(-/-) mice. Although cholecystokinin-stimulated amylase secretion was not significantly different, endocytosis was markedly inhibited in cftr(-/-) compared with WT mice. Cleavage of GP2, a GPI-anchored protein tightly associated with activation of endocytosis, was also decreased. Incubation of lobules from cftr(-/-) mice at pH 8.3 reversed the luminal dilatation. CONCLUSIONS: These data indicate that apical endocytosis is selectively impaired in cftr(-/-) mice, which explains, in part, the luminal dilatation observed at the apical plasma membrane. In vitro alkalinization of luminal fluid led to reversal of defects in membrane dynamics, restored coupled exocytosis and endocytosis, and abolished the luminal dilatation in this animal model of CF. Acidic pH changes in luminal secretions may play a role in the pancreatic membrane dysfunction observed in CF.     

CD34 expression is regulated reciprocally with adhesion molecules in vascular endothelial cells in vitro

Freshly cultured vascular endothelial cells express the CD34 antigen in a diffuse cell surface pattern with some concentration on microvilli. Expression is downregulated with proliferation in continuous culture and undetectable after nine population doublings but can be maintained by restraining cell proliferation and promoting cell contact. Expression of CD34 at the antigen and mRNA levels on early passage cells is rapidly downregulated by interleukin-1 beta (IL-1 beta), interferon-gamma (INF-gamma), and tumor necrosis factor-alpha (TNF- alpha) under conditions in which these ligands upregulate the adhesion molecules: endothelial leukocyte adhesion molecule 1 (ELAM-1) and intracellular adhesion molecule 1 (ICAM-1). This reciprocal pattern of expression and the topographic distribution of CD34 molecules on the lumenal interdigitated microprocesses of adjacent endothelial cells in vivo suggest that CD34 might have a negative modulating role on adhesion functions of endothelia.     

In vivo assessment of intraplaque and endothelial fibrin in ApoE(-/-) mice by molecular MRI

ObjectiveMolecular magnetic resonance imaging (MRI) has emerged as a promising non-invasive modality to characterize atherosclerotic vessel wall changes on a morphological and molecular level. Intraplaque and endothelial fibrin has recently been recognized to play an important role in the progression of atherosclerosis. This study aimed to investigate the feasibility of intraplaque and endothelial fibrin detection using a fibrin-targeted contrast-agent, FTCA (EPIX Pharmaceuticals, Lexington, MA), in a mouse model of atherosclerosis.MethodsMale apolipoproteinE-knockout mice (ApoE^?/?) were fed a high fat diet (HFD) for one to three months. MRI of the brachiocephalic artery was performed prior to and 90 min after the administration of FTCA (n = 8 per group). Contrast to noise ratios (CNR) and longitudinal relaxation rates (R1) of plaques were determined and compared to ex vivo fibrin density measurements on immunohistological sections stained with a fibrin-specific antibody and gadolinium concentrations measured by inductively coupled mass spectroscopy (ICP-MS).ResultsMolecular MRI after FTCA administration demonstrated a significant increase (p < 0.05) in contrast agent uptake in brachiocephalic artery plaques. In vivo CNR measurements were in good agreement with ex vivo fibrin density measurements on immunohistochemistry (y = 2.4x + 11.3, R² = 0.82) and ICP-MS (y = 0.95x + 7.1, R² = 0.70). Late stage atherosclerotic plaques displayed the strongest increase in CNR, R1, ex vivo fibrin staining and gadolinium concentration (p < 0.05).ConclusionThis study demonstrated the feasibility of intraplaque and endothelial fibrin imaging using FTCA. Direct in vivo fibrin detection and quantification could be useful for characterization and staging of coronary and carotid atherosclerotic lesions, which may aid diagnosis and intervention.     

5-脂氧合酶激活蛋白在介导细胞因子诱导血管内皮细胞黏附分子表达中的作用

目的研究5-脂氧合酶激活蛋白（FLAP）在细胞因子诱导血管内皮细胞表达黏附分子中的介导作用,以及MK886对血管内皮细胞表达黏附分子的抑制作用。方法分离并原代培养人脐静脉血管内皮细胞,用FLAP微小强有力RNA（small interfering RNA,siRNA）抑制FLAP的表达,或用MK886抑制FLAP的活性,采用肿瘤坏死因子α（TNF-α）和白细胞介素1β（IL-1β）刺激血管内皮细胞,通过Western杂交和酶联免疫吸附检测血管细胞黏附分子-1（VCAM-1）、细胞间黏附分子- 1（ICAM-1）和E选择素的表达。结果人脐静脉血管内皮细胞能表达低水平的黏附分子,在细胞因子的刺激下黏附分子的表达水平提高。FLAP表达抑制后,细胞因子诱导黏附分子表达的作用降低。细胞因子刺激12 h后,同未处理细胞表达的黏附分子比较,不同黏附分子表达分别增加了6～51倍;用不同浓度MK886处理后,细胞表达的黏附分子水平明显下降,并呈MK886剂量依赖性。结论FLAP介导了细胞因子诱导血管内皮细胞表达黏附分子的作用,MK886具有抑制血管内皮细胞表达黏附分子的作用。     

Accelerated arteriosclerosis of vein grafts in inducible NO synthase(-/-) mice is related to decreased endothelial progenitor cell repair

Inducible NO synthase (iNOS) is expressed by macrophages and smooth muscle cells in atherosclerotic lesions. Previously, we have established a mouse model for vein graft arteriosclerosis by grafting autologous jugular veins or vena cava to carotid arteries. Using this model, we studied the role of iNOS in the development of vein graft arteriosclerosis in iNOS(-/-) mice. Four weeks after grafting, neointimal hyperplasia of vein grafts in iNOS(-/-) mice was increased 2-fold compared with that of wild-type controls. Neointimal lesions contained mainly MAC-1+ macrophages and alpha-actin+ smooth muscle cells (SMCs) in both vein grafts of iNOS(-/-) and iNOS(+/+) mice. Immunofluorescence analysis revealed that increased iNOS expression in neointimal macrophages and SMCs of wild-type, but not iNOS(-/-), mice coincided with increased vascular endothelial growth factor (VEGF) expression in vein grafts. When vein grafts were performed in iNOS(-/-)/TIE2-LacZ transgenic mice expressing LacZ gene only in endothelial cells, the number of beta-galactosidase+ cells in iNOS(-/-) vein grafts were significantly decreased. Furthermore, treatment with the NOS inhibitor NG-nitro-L-arginine methyl ester resulted in delayed endothelial progenitor cell attachment, whereas L-arginine intake through drinking water enhanced endothelial repair. Interestingly, local application of VEGF to iNOS(-/-) vein grafts restored endothelial progenitor homing and reduced neointimal lesions, whereas the VEGF receptor inhibitor SU1498 increased the lesion formation. Additionally, iNOS-deficient SMCs showed a low level of VEGF production in response to interleukin 1beta stimulation. Thus, iNOS deficiency accelerates neointima formation by abrogating VEGF production and endothelial progenitor cell attachment and differentiation.     

Reduced plaque formation induced by rosiglitazone in an STZ-diabetes mouse model of atherosclerosis is associated with downregulation of adhesion molecules

Adhesion molecules have been implicated in the development and progression of cardiovascular disease, which is highly prevalent in people with diabetes. Adhesion molecules can mediate adhesion of leukocytes to the endothelium. Furthermore, P-selectin expressed on platelets is able to mediate the adhesion of leukocytes to platelets. In this study, we examine the in-vivo and in-vitro effects of rosiglitazone with particular emphasis on three important adhesion molecules (VCAM-1, ICAM-1 and P-selectin). In the aorta of STZ-diabetic apolipoprotein E-deficient (apoE KO) mice, rosiglitazone significantly reduced both total and arch plaque area. The mechanism for this appeared to be reduced macrophage infiltration into the atherosclerotic plaque which was also associated with reduced mRNA levels for VCAM-1, ICAM-1, MCP-1 and P-selectin in the aorta. In-vitro studies revealed reduced cell adhesion of monocytic cells (THP-1) to fibrinogen and endothelial cells (HUVEC) after incubation with rosiglitazone. Furthermore, the reduction in leukocyte adhesion also correlated with significant reductions in mRNA levels for VCAM-1, ICAM-1 and P-selectin indicating that reduced macrophage infiltration in atherosclerotic plaques may occur as a result of a direct effect of rosiglitazone on adhesion molecules in both monocytes and endothelial cells. Thus, we have shown that rosiglitazone appears to have direct anti-atherosclerotic effects in an animal model of diabetes-associated atherosclerosis which are at least partly due to effects on VCAM-1, ICAM-1, MCP-1 and P-selectin expression which leads to decreased leukocyte adhesion and macrophage infiltration.     

Serum phosphate is associated with aortic valve calcification in the Multi-ethnic Study of Atherosclerosis (MESA)

Objectives

This study sought to investigate associations of phosphate metabolism biomarkers with aortic valve calcification (AVC).

Background

Calcific aortic valve disease (CAVD) is a common progressive condition that involves inflammatory and calcification mediators. Currently there are no effective medical treatments, but mineral metabolism pathways may be important in the development and progression of disease.

Methods

We examined associations of phosphate metabolism biomarkers, including serum phosphate, urine phosphate, parathyroid hormone (PTH) and serum fibroblast growth factor (FGF)-23, with CT-assessed AVC at study baseline and in short-term follow-up in 6814 participants of the Multi-Ethnic Study of Atherosclerosis (MESA).

Results

At baseline, AVC prevalence was 13.2%. Higher serum phosphate levels were associated with significantly greater AVC prevalence (relative risk 1.3 per 1 mg/dL increment, 95% confidence incidence: 1.1 to 1.5, p < 0.001). Serum FGF-23, serum PTH, and urine phosphate were not associated with prevalent AVC. Average follow-up CT evaluation was 2.4 years (range 0.9–4.9 years) with an AVC incidence of 4.1%. Overall, phosphate metabolism biomarkers were not associated with incident AVC except in the top FGF-23 quartile.

Conclusions

Serum phosphate levels are significantly associated with AVC prevalence. Further study of phosphate metabolism as a modifiable risk factor for AVC is warranted.     

Poor coronary collateral circulation is associated with higher concentrations of soluble adhesion molecules in patients with single-vessel disease

OBJECTIVE: As the endothelium and inflammatory cells play a crucial role in the development of collaterals after a sudden or slowly progressing stenosis of coronary arteries, the levels of soluble endothelial adhesion molecules (CAMs) including vascular cell adhesion molecule (VCAM-1) intercellular adhesion molecule-1 (ICAM-1) and E-selectin were compared between patients with poor coronary collaterals and patients with well-developed collaterals. METHODS: In the study, 97 non-diabetic subjects with single-vessel disease were included. Collateral supply to the stenotic coronary artery was determined by angiographic grading system of 0-3 (Rentrop et al. J Am Coll Cardiol 1985; 5:587-592). Serum levels of adhesion molecules were measured by enzyme-linked immunosorbent assay. RESULTS: Patients were divided into two groups according to the collateral degree (group A: 50 patients with grade 0 and 1; group B: 47 patients with grade 2 and 3 collaterals). The groups were well matched with respect to baseline clinical and angiographic characteristics. Levels of soluble VCAM-1 (mean+/-SEM; 875+/-26.6 versus 742.7+/-35.1 ng/ml; P=0.004), ICAM-1 (322.4+/-12.4 versus 269.4+/-13.3 ng/ml; P=0.005), and E-selectin (43.6+/-2.6 versus 33+/-2.4 ng/ml; P=0.004) were found to be significantly higher in group A in comparison with group B. In addition, when patients were divided into four groups according to the collateral degree, patients with grade 0 collaterals had the highest values and those with grade 3 collaterals had the lowest values for all these molecules. CONCLUSIONS: We concluded that poor collateral circulation is associated with increased levels of soluble CAMs in patients with obstructive coronary artery disease. However, further studies are needed to elucidate the exact role of these inflammatory markers in the setting of poor collateral circulation.