Enzyme May Indicate Predisposition to Cardiovascular Disease

Redox-related plasma proteins are candidate reporters of protein signatures associated with endothelial structure/function. Thiol-proteins from protein disulfide isomerase (PDI) family are unexplored in this context.

Measuring the blood plasma levels of an enzyme called PDIA1 could one day become a method of diagnosing a person's predisposition to cardiovascular disease even if they are healthy, that is those who are not obese, diabetic or a smoker, and with normal cholesterol.

Biochemists from the University of São Paulo (Sao Paulo, SP, Brazil) and their colleagues analyzed blood plasma samples from 35 healthy volunteers with no history of chronic or acute disease. None was a smoker or a user of recreational drugs or chronic medication. They also measured the levels of PDIA1 in 90 plasma bank samples from patients with chronic cardiovascular disease.

Soluble PDI antigen was measured using the Human P4HB Pair Set enzyme-linked immunosorbent assay (ELISA). The optical density of each well was determined immediately using the microplate reader SpectraMax-340, set to 450 nm. The team used a plethora of other methods in the study including Western-Blot analysis, immunoprecipitation, and measurement of PDI reductase activity, cell culture, and cell viability assessment. The team then then conducted several additional proteomic studies to investigate how the plasma levels of PDIA1 correlated with an individual's protein signature. The adhesion and migration of cultured vein endothelial cells treated with PDIA1-poor plasma were impaired in comparison with those of cells treated with PDIA1-rich plasma.

These results led to the hypothesis that the plasma level of PDIA1 could be a window onto individual plasma protein signatures associated with endothelial function, which could indicate a possible predisposition to cardiovascular disease. The study also showed no correlation between PDIA1 levels and well-known risk factors for cardiovascular disease, such as triglycerides and cholesterol. Platelet function was similar among individuals with PDI-rich versus PDI-poor plasma. Remarkably, such protein signatures closely correlated with endothelial function and phenotype, since cultured endothelial cells incubated with PDI-poor or PDI-rich plasma recapitulated gene expression and secretome patterns in line with their corresponding plasma signatures. Patients with cardiovascular events had lower PDI levels than healthy individuals.

The authors concluded that their results reinforce that plasma proteins including PDI are both contributors and accessible reporters of disease-associated conditions and provide evidence that these concepts also extend to healthy individuals. The study was published in the April 2019 issue of the journal Redox Biology.

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