Irreversible posttranslational modifications: potential cardiovascular risk factors. Result and insights fromthe SFB/TRR219

Despite a wide range of pharmaceuticals for the primary prevention of cardiovascular diseases (CVD), such as lipid-lowering drugs, blood pressure-lowering drugs and antidiabetics, CVD remain the most frequent cause of death worldwide. This raises the question of new/additional risk factors besides the well-known traditional ones, such as hypercholesterolemia, hypertension and diabetes mellitus. With the continuous mass-spectrometric identification and functional characterization of non-enzymatic post-translationally modified isoforms of proteins and lipoproteins, it is becoming increasingly clearer that irreversible post-translational modifications (PTM) alter the biological functions of native proteins and lipoproteins and transform them into potential cardiovascular risk factors. In particular, chronic kidney disease (CKD) leads to systemically elevated levels of reactive metabolites and thus to an increased formation of non-enzymatic PTM, which promotes the development of uremic complications, especially cardiovascular diseases; however, non-enzymatic PTMs are not only involved in the genesis and progression of CVD in uremic patients and thus represent a significant and novel cardiovascular risk marker. These findings open up potential new options for risk assessment, prevention and treatment of the patients concerned.