thymosin-beta(4) and Atherosclerosis

Malnutrition-inflammation-atherosclerosis (MIA) syndrome may worsen the prognosis of peritoneal dialysis (PD) patients. Serum thymosin β4 (sTβ4) protects against inflammation, fibrosis and cardiac dysfunction.. The present study aimed to characterize the association between sTβ4 and MIA syndrome as well as to investigate the potential of regulating sTβ4 to improve the prognosis of PD patients.. We performed a cross-sectional, single-center pilot study involving 76 PD patients. Demographic characteristics, clinical characteristics, nutritional profiles, inflammatory mediators, atherosclerosis-related factors and sTβ4 levels were collected and subjected to association analysis for sTβ4 and MIA syndrome.. sTβ4 levels did not significantly vary with sex or primary disease in PD patients. Ages and PD features did not vary between patients with different levels of sTβ4. PD patients with higher levels of sTβ4 had significantly higher levels of nutritional indicators, including subjective global nutritional assessment (SGA) (. The sTβ4 level decreases in PD patients with MIA syndrome. The prevalence of MIA syndrome decreases significantly as the level of sTβ4 increases in PD patients.

Topics: Atherosclerosis; Biomarkers; C-Reactive Protein; Cross-Sectional Studies; Humans; Inflammation; Kidney Failure, Chronic; Malnutrition; Peritoneal Dialysis; Pilot Projects; Serum Albumin

Atherosclerosis is a progressive, degenerative vascular disease and a leading cause of morbidity and mortality. In response to endothelial damage, platelet derived growth factor (PDGF)-BB induced phenotypic modulation of medial smooth muscle cells (VSMCs) promotes atherosclerotic lesion formation and destabilisation of the vessel wall. VSMC sensitivity to PDGF-BB is determined by endocytosis of Low density lipoprotein receptor related protein 1 (LRP1)-PDGFR β complexes to balance receptor recycling with lysosomal degradation. Consequently, LRP1 is implicated in various arterial diseases. Having identified Tβ4 as a regulator of LRP1-mediated endocytosis to protect against aortic aneurysm, we sought to determine whether Tβ4 may additionally function to protect against atherosclerosis, by regulating LRP1-mediated growth factor signalling. By single cell transcriptomic analysis, Tmsb4x, encoding Tβ4, strongly correlated with contractile gene expression and was significantly down-regulated in cells that adopted a modulated phenotype in atherosclerosis. We assessed susceptibility to atherosclerosis of global Tβ4 knockout mice using the ApoE

Topics: Animals; Apolipoproteins E; Atherosclerosis; Becaplermin; LDL-Receptor Related Proteins; Lipoproteins, LDL; Mice; Muscle, Smooth, Vascular

The molecular anatomy of healthy and atherosclerotic tissue is pursued here to identify ongoing molecular changes in atherosclerosis development. Subclinical atherosclerosis cannot be predicted and novel therapeutic targets are needed. Mass spectrometry imaging (MSI) is a novel unexplored ex vivo imaging approach in CVD able to provide in-tissue molecular maps. A rabbit model of early atherosclerosis was developed and high-spatial-resolution MALDI-MSI was applied to comparatively analyze histologically-based arterial regions of interest from control and early atherosclerotic aortas. Specific protocols were applied to identify lipids and proteins significantly altered in response to atherosclerosis. Observed protein alterations were confirmed by immunohistochemistry in rabbit tissue, and additionally in human aortas. Molecular features specifically defining different arterial regions were identified. Localized in the intima, increased expression of SFA and lysolipids and intimal spatial organization showing accumulation of PI, PG and SM point to endothelial dysfunction and triggered inflammatory response. TG, PA, SM and PE-Cer were identified specifically located in calcified regions. Thymosin β4 (TMSB4X) protein was upregulated in intima versus media layer and also in response to atherosclerosis. This overexpression and localization was confirmed in human aortas. In conclusion, molecular histology by MS Imaging identifies spatial organization of arterial tissue in response to atherosclerosis.

Topics: Animals; Aorta; Atherosclerosis; Disease Models, Animal; Humans; Lipids; Mass Spectrometry; Rabbits; Thymosin; Tunica Intima; Vascular Calcification