Bioinformatic Analysis of the Proteome in Exosomes Derived From Plasma: Exosomes Involved in Cholesterol Metabolism Process of Patients With Spinal Cord Injury in the Acute Phase

Abstract

Spinal cord injury (SCI) is a common but severe disease caused by traffic accidents. Coronary atherosclerotic heart disease (CHD) caused by dyslipidemia is known as the leading cause of death in patients with SCI. However, the quantitative analysis showed that the cholesterol and lipoprotein concentrations in peripheral blood (PB) did not change significantly within 48 h after SCI. Due to the presence of the Blood spinal cord barrier (BSCB), there are only few studies concerning the plasma cholesterol metabolism in the acute phase of SCI. Exosomes have a smaller particle size, which enables them relatively less limitation of BSCB. This study uses exosomes derived from the plasma of 43 patients in the acute phase of SCI and 71 patients in the control group as samples. MS proteomics and bioinformatics analysis found 590 quantifiable proteins, in which 75 proteins were upregulated and 153 proteins were downregulated, and the top 10 differentially expressed proteins are those including downregulating proteins: HIST1H4A, HIST2H3A, HIST2H2BE, HCLS1, S100A9, HIST1H2BM, S100A8, CALM3, YWHAH, and SFN, and upregulating proteins: SERPIND1, C1QB, SPTLC3, IGHV4-28, C4A, IGHV4-38-2, IGHV4-30-2, SLC15A1, C4B, and ACTG2. Enrichment analysis showed that the largest part of proteins was related to cholesterol metabolism among the downregulated proteins. The main components of cholesterol [ApoB-48 and ApoB-100 increased, ApoA-I, ApoA-II, ApoA-IV, ApoC, ApoE, and Apo(a) decreased] were changed in exosomes derived from plasma of patients. ELISA analysis showed that some components were disordered in the acute phase of SCI. These results suggested that the exosomes might be involved in cholesterol metabolism regulation in the acute phase of SCI.

Mesenchymal stem cell‐exosome‐mediated matrix metalloproteinase 1 participates in oral leukoplakia and carcinogenesis by inducing angiogenesis

“…These results suggest that plasma exosomes are involved in the regulation of lipid metabolism in the acute stage of spinal cord injury, and may be involved in the regulation of metabolic reprogramming of tissue microenvironments in other diseases. 26 In our study, we knocked down MMP1 in OLK-MSCs and Ca-MSCs using siRNA, and might have changed the other content of exosomes; more convincing evidence should be provided by either direct knockout exclusion of MMP1 or via MMP1-specific immune neutralization in exosomes. Future studies should focus on identifying the key downstream molecules and pathways to better understand the significance of exosomal MMP1 in preparing the precancerous and premetastatic niche.…”

“…For instance, studies have reported that APOB does not change significantly in the peripheral blood of patients with acute spinal cord injury, however, APOB expression in peripheral plasma exosomes increases significantly. These results suggest that plasma exosomes are involved in the regulation of lipid metabolism in the acute stage of spinal cord injury, and may be involved in the regulation of metabolic reprogramming of tissue microenvironments in other diseases 26 …”

Ageing related thyroid deficiency increases brain-targeted transport of liver-derived ApoE4-laden exosomes leading to cognitive impairment

“…This transport, however, can be mediated by exosomes, which were reported to carry nucleic acid and proteins across BBB [ 13 ]. The existence of ApoE in the human plasma exosomes has been also reported recently [ 14 ]. Vacuolar ATPases (V-ATPases) are ATP-dependent proton pumps, highly expressed in the ruffled border membranes to acidify the resorption lacunae [ 15 ].…”

Identified lncRNAs functional modules and genes in prediabetes with hypertriglyceridemia by weighted gene co-expression network analysis

“…Therefore, the mRNA HIST1H2BM in the above pathways might play a role in participating in lipid metabolism. Moreover, the downregulating protein HIST1H2BM was also found that may be involved in regulating lipid metabolism or other signaling pathways in the acute phase of spinal cord injury [ 38 ].…”