Serum matrix metalloproteinase-2 and increased oxidative stress are associated with carotid atherosclerosis in hemodialyzed patients

Pawlak, Krystyna; Pawlak, Dariusz; Myśliwiec, M

doi:10.1016/j.atherosclerosis.2006.01.020

Cited by 50 publications

(52 citation statements)

References 26 publications

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“…Our observation of an increased incidence of neointimal formation is concordant with the current literature that suggests that MMP-2 activation is a strong independent variable linked to intima-media thickness in dialyzed patients. 11,12,19,25 The significant correlation between arterial stiffness and calcium deposition in the A dialyzed is also concordant with other investigations. It has been shown that vascular calcification in dialyzed patients was associated with increased stiffness of large-capacity, elastic-type arteries like the aorta, brachial artery, and common carotid artery.…”

Section: Chung Et Al Ckd Upregulates Mmp-2 In Artery 797supporting

confidence: 89%

“…Exposure to dialysis treatments would lead to abnormalities in metabolic, humoral, inflammatory, and hemodynamic factors (eg, chronic volume overload, oxidative stress, vitamin D deficiency, hyperphosphatemia, hyperhomocysteinemia, and upregulation of cytokines, growth factors, and C-reactive protein), which are known to be promoters of MMP-2 activation. 1,12,[25][26][27][28] Moreover, our observation suggests that MMP-2 may be more profoundly and quickly upregulated by the HD procedure. However, future studies need to measure MMP-2 activity from tissue and blood at the beginning of dialysis in different modalities (eg, HD and PD) and follow those levels over time before definite statements can be made.…”

Section: Chung Et Al Ckd Upregulates Mmp-2 In Artery 797mentioning

confidence: 97%

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Upregulation of Matrix Metalloproteinase-2 in the Arterial Vasculature Contributes to Stiffening and Vasomotor Dysfunction in Patients With Chronic Kidney Disease

et al. 2009

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Background-Cardiovascular disease is the leading cause of mortality in chronic kidney disease patients on maintenance dialysis. Given the importance of matrix metalloproteinase-2 (MMP-2) in matrix integrity, vascular cell function, and structural stability, we hypothesized that MMP-2 was elevated in the macrovasculature in dialyzed chronic kidney disease patients compared with chronic kidney disease patients not on dialysis and kidney donors.

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Section: Chung Et Al Ckd Upregulates Mmp-2 In Artery 797supporting

confidence: 89%

Section: Chung Et Al Ckd Upregulates Mmp-2 In Artery 797mentioning

confidence: 97%

Upregulation of Matrix Metalloproteinase-2 in the Arterial Vasculature Contributes to Stiffening and Vasomotor Dysfunction in Patients With Chronic Kidney Disease

et al. 2009

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“…21,22 MMP-2 levels have also previously been strongly associated with APWV in a hypertensive but otherwise healthy cohort. 23 Similarly, existing data on EDPs indicate a strong correlation with age and history of CVD.…”

Section: Discussionmentioning

confidence: 91%

Elastin Degradation Is Associated With Progressive Aortic Stiffening and All-Cause Mortality in Predialysis Chronic Kidney Disease

et al. 2012

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Abstract-In the large conduit arteries, elastin is important in maintaining vascular compliance. Studies in animal models suggest that elastin degradation may promote arteriosclerotic vascular changes. There is already a well-established link between aortic stiffening and mortality in the general population and in patients undergoing dialysis. Elastin degradation is mediated by several proteases, including matrix metalloproteinase 2 and cathepsin S. Elastin turnover may be inferred by measuring serum levels of elastin-derived peptides. We analyzed the serum concentration of these biomarkers, their endogenous inhibitors, and aortic pulse wave velocity in 200 patients with stages 3 and 4 chronic kidney disease and then serially in a subgroup of 65 patients over 36 months. Serum matrix metalloproteinase 2, cathepsin S, and elastin-derived peptide levels were independently associated with baseline aortic pulse wave velocity and changes in stiffness over the follow-up period. Higher matrix metalloproteinase 2 and elastin-derived peptide levels were also independently associated with preexisting cardiovascular disease. In multivariable Cox regression, higher serum elastin-derived peptide levels were independently associated with increased all-cause mortality (hazard ratio per SD increaseϭ1.78; Pϭ0.021). In predialysis chronic kidney disease, elastin degradation is an important determinant of arterial stiffness and is associated with all-cause mortality. 1 Loss of elastin leads to an increase in the collagen:elastin ratio and augmented mechanical loading of stiffer collagen fibers. With age, vascular smooth muscle cells (VSMCs) become less contractile, and there are increased rates of cellular senescence and death.2 Together, these changes contribute to the loss of intrinsic elasticity and progressive stiffening of the arterial wall.3 In addition to promoting arteriosclerosis, elastin degradation also stimulates intimal VSMC invasion, neointima formation, and plaque destabilization and, thus, may also be an important factor in the pathogenesis of atherosclerotic disease. Age-associated arterial remodeling is accelerated in patients with chronic kidney disease (CKD), who have a vastly elevated cardiovascular risk compared with the general population. 5 Although not a universal finding, arterial stiffness, as measured by various methods, has been associated with decline in renal function in patients with CKD 6-8 and is a strong predictor of cardiovascular risk and all-cause mortality in patients with end-stage renal failure 9 and in non-CKD populations. 10Extracellular matrix turnover is mediated by a number of elastolytic proteinases, including Zn 2ϩ /Ca 2ϩ -dependent matrix metalloproteinases (MMPs; eg, MMP-2) and cathepsin cysteine proteases, such as cathepsin S. These proteases are mainly secreted by activated macrophage, resident myofibroblasts, or VSMCs but are also expressed intracellularly in a wide range of cell types. 4 The activities of MMP-2 and cathepsin S are partly regulated by the concentration of endog...

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“…The progression of atherosclerosis and PEW in such patients is accelerated by various factors, in particular oxidative stress and inflammation. Oxidative stress is closely associated with advancing atherosclerosis (2) and is a principal risk factor for cardiovascular mortality in patients on HD (3). Such patients develop uremic syndrome per se or factors associated with uremia and an excessively inflamed state with marked hypoalbuminemia (4).…”

mentioning

confidence: 99%

Assessment of Myeloperoxidase and Oxidative α1-Antitrypsin in Patients on Hemodialysis

Honda¹,

Ueda²,

Kojima³

et al. 2009

Clinical Journal of the American Society of Nephrology

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Background and objectives: The present study assesses the effects of the oxidative stress marker, myeloperoxidase (MPO), and the possible MPO-related oxidative stress marker, oxidative ␣ 1 -antitrypsin (oxAT), on carotid intima-media thickness (CIMT) and protein-energy wasting (PEW) in patients on hemodialysis (HD).Design, setting, participants, & measurements: Blood samples were obtained from 383 patients before HD to measure WBC count, serum albumin, lipids, high-sensitivity C-reactive protein (CRP), ␣ 1 -antitrypsin (AT), interleukin-6, oxidative LDL-C, MPO, and oxAT. We assessed both CIMT and the geriatric nutritional risk index (GNRI) in this cross-sectional competitive study.Results: Levels of MPO and oxAT correlated. Myeloperoxidase was associated with max-CIMT, and oxAT correlated with max-CIMT and GNRI. Multivariate linear regression models showed that MPO and oxAT were independent predictors of increasing max-CIMT, whereas oxAT, but not MPO, independently correlated with GNRI. In four combined MPO and oxAT groups classified according to median values, a multinomial logistic regression model showed that high MPO together with high oxAT was independently associated with increased max-CIMT. Moreover, the OR for max-CIMT with positive PEW and high MPO was significantly increased in the four groups with combined MPO and PEW.Conclusions: High MPO with high oxAT and high MPO with PEW seem to contribute to plaque formation in patients on HD, whereas elevated MPO or oxAT alone might not predict increasing CIMT. In contrast, a high oxAT value seems to be an independent predictor of PEW in patients on HD.

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Serum matrix metalloproteinase-2 and increased oxidative stress are associated with carotid atherosclerosis in hemodialyzed patients

Cited by 50 publications

References 26 publications

Upregulation of Matrix Metalloproteinase-2 in the Arterial Vasculature Contributes to Stiffening and Vasomotor Dysfunction in Patients With Chronic Kidney Disease

Upregulation of Matrix Metalloproteinase-2 in the Arterial Vasculature Contributes to Stiffening and Vasomotor Dysfunction in Patients With Chronic Kidney Disease

Elastin Degradation Is Associated With Progressive Aortic Stiffening and All-Cause Mortality in Predialysis Chronic Kidney Disease

Assessment of Myeloperoxidase and Oxidative α1-Antitrypsin in Patients on Hemodialysis

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