β2-Microglobulin as a Biomarker in Peripheral Arterial Disease

Wilson, Andrew; Kimura, Eiichiro; Harada, Randall K; Nair, Nandini; Narasimhan, Balasubramanian; Meng, Xiao; Zhang, Fujun; Beck, Kendall; Olin, Jeffrey W.; Fung, Eric T.; Cooke, John P.

doi:10.1161/circulationaha.106.683722

Cited by 168 publications

(102 citation statements)

References 38 publications

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“…18 In patients on HD, serum b 2 M is markedly increased and predicts all-cause mortality, 19,20 but studies on the relationship between serum b 2 M and cardiovascular disease are limited. It has been reported that serum b 2 M correlates with carotid IMT 21 and the number of calcified valves.…”

Section: Discussionmentioning

confidence: 99%

Differences in associated factors between aortic and mitral valve calcification in hemodialysis

et al. 2010

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Increased prevalence of aortic and mitral valve calcification has been reported in patients on hemodialysis, but it remains unknown whether aortic and mitral valve calcification arise from similar pathogenesis. We detected heart valve calcification using two-dimensional echocardiography, and we related valve calcification to various clinical parameters in patients treated with hemodialysis three times a week for more than 1 year. In 112 patients (77 men and 35 women, age 67±10 years, duration on hemodialysis 95 ± 67 months), aortic and mitral valve calcification were observed in 84 (75.0%) and 58 (51.7%) patients, respectively. Aortic valve calcification was associated with increased age, higher serum calcium, lower serum albumin, lower total cholesterol and higher high-sensitivity C-reactive protein. Multivariate analysis showed that increased age and higher serum calcium were independently associated with aortic valve calcification. Conversely, mitral valve calcification was associated with increased age, higher high-sensitivity C-reactive protein and higher serum b 2 -microglobulin, but not with higher serum calcium. In multivariate analysis, increased age and higher serum b 2 -microglobulin were independently associated with mitral valve calcification. Serum b 2 -microglobulin was associated with longer duration on hemodialysis, malnutrition inflammation (lower serum albumin and higher high-sensitivity C-reactive protein) and dyslipidemia. Considering the results in previous studies showing that the distribution of b 2 -microglobulin amyloid deposition was consistent with that of tissue calcification in patients on hemodialysis, b 2 -microglobulin may have pathogenic roles in valve calcification.

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Section: Discussionmentioning

confidence: 99%

Differences in associated factors between aortic and mitral valve calcification in hemodialysis

et al. 2010

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“…29,[34][35][36][37][38][39][40][41] A full discussion of these nontraditional risk factors is beyond the scope of this review.…”

Section: Nontraditional Risk Factorsmentioning

confidence: 99%

Peripheral Artery Disease: Current Insight Into the Disease and Its Diagnosis and Management

Olin

Sealove

2010

Mayo Clinic Proceedings

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“…6 The importance of a healthy endothelium is seen in cardiovascular and metabolic diseases, where endothelial dysfunction is associated with atherosclerosis, hypertension, and the metabolic syndrome. [7][8][9] Important in the development of such endothelial dysfunction are oxidative stress 10,11 and inflammation, 12,13 both of which are common in the pathogenesis of cardiovascular diseases.…”

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confidence: 99%

Atorvastatin Restores Endothelial Function in Offspring of Protein-Restricted Rats in a Cholesterol-Independent Manner

et al. 2009

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Abstract-Maternal protein restriction in rats leads to endothelial dysfunction and decreased NO bioavailability in the offspring. Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) are recognized to have pleiotropic actions including increasing NO bioavailability and reducing inflammation and oxidative damage. This study assessed statin treatment on vascular function in a model of endothelial dysfunction, which is independent of dyslipidemia. Wistar rats were fed a control (18% casein) or protein-restricted (9% casein) diet throughout pregnancy. At weaning, a subset of the protein-restricted group was given atorvastatin (10 mg/kg per day) in the drinking water. At 145 days of age, offspring were euthanized by CO 2 inhalation. Plasma samples were collected for markers of inflammation, vascular reactivity of the thoracic aorta, and small mesenteric arteries were assessed on the wire myograph, and tissues were snap frozen for molecular biology analysis. Thoracic aorta endothelial-dependent vasodilatation was attenuated in the male offspring from both protein-restricted groups compared with controls (PϽ0.05) but was similar in females (P value not significant). Endothelial-dependent dilatation of mesenteric arteries was attenuated in male and female protein-restricted offspring (PϽ0.05) and was corrected by atorvastatin. Maternal protein restriction increased plasma inflammatory markers granulocyte chemotactic protein, lipocalin-2, and ␤ 2 -microglobulin in male and C-reactive protein in female offspring (PϽ0.05). Atorvastatin had no effect on inflammatory markers in the males but restored C-reactive protein to control levels in the females (PϽ0.05). Aortic and mesenteric artery mRNA levels of endothelial NO synthase, superoxide dismutase 1, and tumor necrosis factor-␣ were unchanged. These data suggest that atorvastatin can restore endothelial function in this model, but its effects are gender specific and dependent on the vascular bed. Key Words: statins (atorvastatin) Ⅲ experimental models Ⅲ fetal programming Ⅲ vascular biology Ⅲ endothelium Ⅲ nitric oxide Ⅲ inflammation T here is considerable evidence that the etiology of cardiovascular and metabolic diseases has origins partly in the developmental environment. 1 A widely used animal model to study this phenomenon is the rat, in which the restriction of dietary protein during pregnancy leads to raised blood pressure and endothelial dysfunction in the offspring. [2][3][4] Increasingly, evidence from this model points to a disruption to the NO pathway as a key component of the underlying pathophysiology. 4,5 The healthy vascular endothelium plays an important role in maintaining vascular tone through the release of factors including NO, prostacyclin, and endothelial-derived hyperpolarizing factor. 6 The importance of a healthy endothelium is seen in cardiovascular and metabolic diseases, where endothelial dysfunction is associated with atherosclerosis, hypertension, and the metabolic syndrome. 7-9 Important in the development of such endothelial ...

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β2-Microglobulin as a Biomarker in Peripheral Arterial Disease

Cited by 168 publications

References 38 publications

Differences in associated factors between aortic and mitral valve calcification in hemodialysis

Differences in associated factors between aortic and mitral valve calcification in hemodialysis

Peripheral Artery Disease: Current Insight Into the Disease and Its Diagnosis and Management

Atorvastatin Restores Endothelial Function in Offspring of Protein-Restricted Rats in a Cholesterol-Independent Manner

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