Proteomic Profiling of Leukocytes Reveals Dysregulation of Adhesion and Integrin Proteins in Chronic Kidney Disease-Related Atherosclerosis

A progressive
loss of functional nephrons defines chronic kidney
disease (CKD). Complications related to cardiovascular disease (CVD)
are the principal causes of mortality in CKD; however, the acceleration
of CVD in CKD remains unresolved. Our study used a complementary proteomic
approach to assess mild and advanced CKD patients with different atherosclerosis
stages and two groups of patients with different classical CVD progression
but without renal dysfunction. We utilized a label-free approach based
on LC-MS/MS and functional bioinformatic analyses to profile CKD and
CVD leukocyte proteins. We revealed dysregulation of proteins involved
in different phases of leukocytes’ diapedesis process that
is very pronounced in CKD’s advanced stage. We also showed
an upregulation of apoptosis-related proteins in CKD as compared to
CVD. The differential abundance of selected proteins was validated
by multiple reaction monitoring, ELISA, Western blotting, and at the
mRNA level by ddPCR. An increased rate of apoptosis was then functionally
confirmed on the cellular level. Hence, we suggest that the disturbances
in leukocyte extravasation proteins may alter cell integrity and trigger
cell death, as demonstrated by flow cytometry and microscopy analyses.
Our proteomics data set has been deposited to the ProteomeXchange
Consortium via the PRIDE repository with the data set identifier PXD018596.