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

Brighton and Sussex University Hospitals National Health Service Trust, Brighton, United Kingdom.
Hypertension (Impact Factor: 7.63). 03/2012; 59(5):973-8. DOI: 10.1161/HYPERTENSIONAHA.111.187807
Source: PubMed

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 increase=1.78; P=0.021). In predialysis chronic kidney disease, elastin degradation is an important determinant of arterial stiffness and is associated with all-cause mortality.

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Available from: Edward R Smith, Feb 15, 2015
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    • "This degradation of elastin may occur slowly over decades, but inflammatory diseases affecting elastic tissue degradation may accelerate this process. Therefore, DES and IDS have been proposed as biomarkers useful to selectively monitor the degradation of elastin in diseases such as chronic obstructive pulmonary disease (COPD), abdominal aortic aneurism (AAA), and chronic kidney disease (CKD) [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13]. "
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    • "CatK deficiency has been shown to reduce diet-induced atherosclerotic lesion formation [11]. Recent studies have shown that the levels of serum CatS or CatL were increased in patients with diabetes and chronic kidney disease [12] [13]. These data suggested that Cats levels are associated with atherosclerosis-based cardiovascular disease. "
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