Differential proteomic distribution of TTR (pre-albumin) forms in serum and HDL of patients with high cardiovascular risk

摘要

Inflammation is a common condition contributing to cardiovascular disease progression which leads to clinical manifestations such as acute myocardial infarction (AMI). By applying a proteomic expression profiling approach we have investigated changes in transthyretin (TTR) in AMI-patients and its distribution patterns in HDL samples of patients with high cardiovascular risk, such as those with familiar hypercholesterolemia (FH). Methods and results: The characterization by bidimensional electrophoresis (2-DE), followed by mass-spectrometry (MALDI-TOF) of serum samples revealed changes in the intensity of the TTR spot with a p. I of 5.6 and a Mw of 42. kDa (tTTR) between AMI-patients in association to diabetic dyslipemia. Serum TTR levels, determined by commercial ELISA, were significantly lower (p< 0.0001) in AMI-patients (n= 39) and FH-patients (n= 100) than in healthy controls (n= 60). Western blot and 2-DE analysis showed a differential distribution profile of TTR forms between serum, where 3 TTR forms of 42 (tTTR), 28 (dTTR), and 14. kDa (mTTR) were detected, and HDL samples, where only mTTR was present. Conclusions: Our results demonstrate alterations in TTR proteomic profile in relation to the clustering of risk factors which seems to highlight the implication of TTR in cardiovascular risk. The significant differences in TTR between serum (tTTR) and HDL (mTTR) underscore the importance of TTR-forms in the circulation and deserve further investigation to understand their function.