Role of inflammatory marker YKL-40 in the diagnosis, prognosis and cause of cardiovascular and liver diseases.

This review summarizes present evidence for the role of YKL-40 in the diagnosis, prognosis and cause of cardiovascular and alcoholic liver disease. The question of whether YKL-40 is merely a marker or a causal factor in the development of cardiovascular and liver disease is addressed, with emphasis...

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Publicado en:Critical Reviews in Clinical Laboratory Sciences Vol. 53; no. 6; pp. 396 - 409
Autores principales: Kjaergaard, A. D., Johansen, J. S., Bojesen, S. E., Nordestgaard, B. G.
Formato: review tables/charts Journal Article
Publicado: Taylor & Francis Ltd Dec2016
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Dec2016
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      pub: Taylor & Francis Ltd
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        atl: Role of inflammatory marker YKL-40 in the diagnosis, prognosis and cause of cardiovascular and liver diseases.
      aug:
        au:
          Kjaergaard, A. D.
          Johansen, J. S.
          Bojesen, S. E.
          Nordestgaard, B. G.
        affil: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
      sug:
        subj:
          Liver Diseases, Alcoholic Etiology
          Inflammation
          Cardiovascular Diseases Etiology
          Acute-Phase Proteins
          Cardiovascular Diseases Diagnosis
          Cardiovascular Diseases Prognosis
          Biological Markers
          Liver Diseases, Alcoholic Diagnosis
          Liver Diseases, Alcoholic Prognosis
          Molecular Biology
          Disease Progression
      ab: This review summarizes present evidence for the role of YKL-40 in the diagnosis, prognosis and cause of cardiovascular and alcoholic liver disease. The question of whether YKL-40 is merely a marker or a causal factor in the development of cardiovascular and liver disease is addressed, with emphasis on the Mendelian randomization design. The Mendelian randomization approach uses genetic variants associated with lifelong high plasma YKL-40 levels that are largely unconfounded and not prone to reverse causation. Thus, the approach mimics a controlled double-blind randomized trial, but it uses genetic variants rather than a drug and placebo, and like a blinded trial, it allows inference about causality. Moreover, the review also covers background on the molecular biology and functions of YKL-40, YKL-40 levels in healthy individuals and reference range, and the role of YKL-40 as a biomarker of cardiovascular and alcoholic liver disease. YKL-40 is a plasma protein named after its three N-terminal amino acids, Y (tyrosine), K (lysine) and L (leucine), and its molecular weight of 40 kDa. It is produced by local inflammatory cells in inflamed tissues, such as lipid-laden macrophages inside the vessel wall and perhaps also hepatic stellate cells. Observational studies show that plasma YKL-40 levels are elevated in patients with cardiovascular and liver disease and are associated with disease severity and prognosis. Furthermore, elevated plasma YKL-40 levels in apparently healthy individuals are associated with a 2-fold increased risk of future ischemic stroke and venous thromboembolism, but not with myocardial infarction, suggesting that YKL-40 could play a role in the formation of embolisms rather than atherosclerosisper se. Further, elevated YKL-40 levels combined with excessive alcohol consumption are associated with 10-years risk of alcoholic liver cirrhosis of up to 7%, suggesting that YKL-40 can be used as a strong noninvasive marker of predicting alcoholic liver cirrhosis. Importantly, in Mendelian randomization studies, genetically elevated plasma YKL-40 levels were not associated with risk of cardiovascular and alcoholic liver disease, thus suggesting that plasma YKL-40 does not play a causal role in the development of these diseases. Despite this, plasma YKL-40 levels may play a role in disease progression after diagnosis, and inhibition of YKL-40 activity might be a novel therapy in some cardiovascular and liver diseases.
      pubtype: Academic Journal
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        review
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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