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.

Substantial evidence supports a role of chronic subclinical inflammation and activation of the innate immune system in the pathogenesis of insulin resistance and endothelial dysfunction and the development of type 2 diabetes (T2D) and atherosclerosis. Several proinflammatory cytokines, acute phase-reactants and cell adhesion molecules play a pivotal role in this chronic subclinical inflammation but a comprehensive understanding of the interrelations of these molecules is still needed. YKL-40 is a new inflammatory marker with relation to acute and chronic inflammation as well as cancer. It is secreted in vitro from a variety of human cells, including vascular smooth muscle cells (VSMCs), activated macrophages and macrophages during late stages of differentiation and is found in vivo in subpopulations of macrophages in tissues with inflammation and extracellular tissue remodelling, such as macrophages in atherosclerotic plaques. YKL-40 promotes chemotaxis, cell attachment and migration of VSMCs and the formation of branching tubules suggesting that YKL-40 plays a role in angiogenesis. Latest studies reveal that YKL-40 is elevated in patients with T2D and is related to insulin resistance. This article reviews the studies of YKL-40 with focus on a possible role of YKL-40 in insulin resistance, endothelial dysfunction and atherosclerosis.

Objective and design. YKL-40 participates in infl ammatory states and vascular processes, which implies that comparison can be made with other infl ammatory markers associated with insulin resistance and type 2 diabetes (T2D). In the present study levels of plasma YKL-40 and serum hsCRP were evaluated in patients with T2D. Materials and methods. Patients with T2D and age-matched healthy controls participated in the study. Insulin resistance was estimated using HOMA-IR model. Biochemical parameters were measured in venous blood after a 10 h fast. Results. Patients with T2D were insulin resistant (p < 0.001) and had raised levels of plasma YKL-40 (p < 0.001) and serum hsCRP (p < 0.001). YKL-40 was correlated with HOMA-IR (r = 0.23, p < 0.01), NEFA (r = 0.32, p < 0.001) and triglycerides (r = 0.24, p < 0.05). YKL-40 and hsCRP were not correlated (r = 0.17, p = NS). All participants with hsCRP < 1 mg/l had higher insulin sensitivity (p < 0.05 and p < 0.01, respectively). HsCRP were predicted by HOMA-IR and BMI (r 2 = 0.48, p < 0.01). Plasma YKL-40 was predicted by HOMA-IR and triglycerides (r 2 = 0.27, p < 0.01). Conclusions. YKL-40 and hsCRP are elevated in patients with T2D and are related to insulin resistance. No correlation was found between YKL-40 and hsCRP indicating that increased levels of YKL-40 occur independently from elevated plasma hsCRP.