YKL-40--an emerging biomarker in cardiovascular disease and diabetes

Abstract

Several inflammatory cytokines are involved in vascular inflammation resulting in endothelial dysfunction which is the earliest event in the atherosclerotic process leading to manifest cardiovascular disease. YKL-40 is an inflammatory glycoprotein involved in endothelial dysfunction by promoting chemotaxis, cell attachment and migration, reorganization and tissue remodelling as a response to endothelial damage. YKL-40 protein expression is seen in macrophages and smooth muscle cells in atherosclerotic plaques with the highest expression seen in macrophages in the early lesion of atherosclerosis. Several studies demonstrate, that elevated serum YKL-levels are independently associated with the presence and extent of coronary artery disease and even higher YKL-40 levels are documented in patients with myocardial infarction. Moreover, elevated serum YKL-40 levels have also been found to be associated with all-cause as well as cardiovascular mortality. Finally, YKL-40 levels are elevated both in patients with type 1 and type 2 diabetes, known to be at high risk for the development of cardiovascular diseases, when compared to non-diabetic persons. A positive association between elevated circulating YKL-40 levels and increasing levels of albuminuria have been described in patients with type 1 diabetes indicating a role of YKL-40 in the progressing vascular damage resulting in microvascular disease. This review describes the present knowledge about YKL-40 and discusses its relation to endothelial dysfunction, atherosclerosis, cardiovascular disease and diabetes and look ahead on future perspectives of YKL-40 research.

Figure 1

Kaplan-Meier-curves of the unadjusted cumulative overall survival according to increasing quartiles of YKL-40 at baseline (59.5 ng/ml). Curves presented from top: The mortality rate was 1) 7.6% for first quartile values of YKL-40 (≤ 39 ng/l); 2) 9.3% for second quartile values of YKL-40 (39.1-59.5 ng/l); 3) 18.5 % for third quartile values of YKL-40 (59.6-111 ng/l), and 4) 29.3 % for four quartile values of YK-40 (> 111 ng/l), p < 0.0001. Y-axis represents the lifetime of the participants during the 5 years follow-up period.

Figure 2

Mean (95% confidence intervals) of ln-transformed YKL-40. Equivalent YKL-40 data (median (interquartile range)), are for macroalbuminuria/diabetic nephropathy (U-albumin > 300 mg/24 h), YKL-40 = 117 (68-215) ng/ml; persistent microalbuminuria (U-albumin 30-300 mg/24 h), YKL-40 = 74 (45-160) ng/ml; normoalbuminuria (U-albumin < 30 mg/24 h), YKL-40 = 53 (32-105) ng/ml; control group, YKL-40 = 37 (29-52) ng/ml. P < 0.001 for all comparisons. Groups were matched according to gender and duration of diabetes (> 30 years).