Label-Free Quantitative Proteomics Reveals Differences in Molecular Mechanism of Atherosclerosis Related and Non-Related to Chronic Kidney Disease

Abstract

The major cause of mortality in patients with chronic kidney disease (CKD) is atherosclerosis related to traditional and non-traditional risk factors. However, the understanding of the molecular specificity that distinguishes the risk factors for classical cardiovascular disease (CVD) and CKD-related atherosclerosis (CKD-A) is far from complete. In this study we investigated the disease-related differences in the proteomes of patients with atherosclerosis related and non-related to CKD. Plasma collected from patients in various stages of CKD, CVD patients without symptoms of kidney dysfunction, and healthy volunteers (HVs), were analyzed by a coupled label-free and mass spectrometry approach. Dysregulated proteins were confirmed by an enzyme-linked immunosorbent assay (ELISA). All proteomic data were correlated with kidney disease development and were subjected to bioinformatics analysis. One hundred sixty-two differentially expressed proteins were identified. By directly comparing the plasma proteomes from HVs, CKD, and CVD patients in one study, we demonstrated that proteins involved in inflammation, blood coagulation, oxidative stress, vascular damage, and calcification process exhibited greater alterations in patients with atherosclerosis related with CKD. These data indicate that the above nontraditional risk factors are strongly specific for CKD-A and appear to be less essential for the development of “classical” CVD.

Clinical Proteomics in Kidney Disease: From Discovery to Clinical Application

“…Using 2DE and MS, as well as direct MS for low molecular weight compounds, the authors found deregulation of blood coagulation cascade, the transport, binding and metabolism of lipoproteins and inflammatory processes in CKD and CVD. These results were later confirmed in an additional study [55].…”

Advanced Oxidation Protein Products and Carbonylated Proteins as Biomarkers of Oxidative Stress in Selected Atherosclerosis-Mediated Diseases

“…In relation to complex etiology of atherosclerosis, the studies on its pathomechanism are still essential and should be continued. Several reports have indicated that two types of atherosclerosis are defined: “classic” associated with cardiovascular disease (CVD) and “nonclassic” CKD [8, 9]. The above-mentioned classification is based on differing mechanisms underlying the formation of CVD- and CKD-related plaques [10].…”

Comparative proteomic profiling of refractory/relapsed multiple myeloma reveals biomarkers involved in resistance to bortezomib-based therapy

“…Ten micrograms of PC protein was digested and prepared for analysis as previously described [ 27 ]. Each sample was prepared for digestion in duplicate.…”

“…Each sample was prepared for digestion in duplicate. For each run, 1.5 μg of the digested protein samples was subjected to nano-LC MS/MS analysis using a Dionex UltiMate 3000 RSLC nano System and Q-Exactive Orbitrap mass spectrometer (Thermo Fisher Scientific, USA), as previously described [ 27 ]. The normalized collision energy was set to 28.…”