angiogenin and Atherosclerosis

Atherosclerosis and its consequences are the leading cause of mortality in the world. For this reason, we have reviewed atherosclerosis biomarkers and selected the most promising ones for review. We focused mainly on biomarkers related to inflammation and oxidative stress, such as the highly sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6), and lipoprotein-associated phospholipase A2 (Lp-PLA2). The microRNA (miRNA) and the usefulness of the bone mineralization, glucose, and lipid metabolism marker osteocalcin (OC) were also reviewed. The last biomarker we considered was angiogenin (ANG). Our review shows that due to the multifactorial nature of atherosclerosis, no single marker is known so far, the determination of which would unambiguously assess the severity of atherosclerosis and help without any doubt in the prognosis of cardiovascular risk.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Atherosclerosis; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Humans; Interleukin-6; Osteocalcin; Prognosis; Ribonuclease, Pancreatic; Risk Factors

ANG (angiogenin) is essential for cellular adaptation to endoplasmic reticulum (ER) stress, a process closely associated with cardiovascular diseases, including atherosclerosis. We aimed to investigate the role of ANG in the progression of atherosclerosis and elucidate its underlying molecular mechanisms.. We constructed adenoassociated virus 9 ANG overexpression vectors and endothelial ANG- and ApoE (apolipoprotein E)-deficient mice to determine the effects of ANG on ER stress and atherosclerotic lesions. RNA sequencing of endothelial ANG- and ApoE-deficient mice identified ANG-dependent downregulation of ST3GAL5 (ST3 beta-galactoside alpha-2,3-sialyltransferase 5) expression, and the direct regulation of ST3GAL5 by ANG was verified by chromatin immunoprecipitation sequencing and luciferase reporter assay results.. Reanalysis of expression profiling datasets indicated decreased ANG levels in patients' atherosclerotic lesions, and these data were validated in aortas from ApoE. These results suggest that endothelial intracellular ANG is a novel therapeutic against atherosclerosis and exerts atheroprotective effects via ST3GAL5-mediated ER stress suppression.

Topics: Animals; Atherosclerosis; Disease Models, Animal; Down-Regulation; Endoplasmic Reticulum Stress; Endothelial Cells; Gene Expression Regulation; Human Umbilical Vein Endothelial Cells; Humans; Mice; Mice, Knockout; Mice, Knockout, ApoE; Models, Cardiovascular; Ribonuclease, Pancreatic; RNA, Messenger; Sialyltransferases; Up-Regulation