The molecular basis of homocysteine thiolactone-mediated vascular disease

2007 ◽  
Vol 45 (12) ◽  
Author(s):  
Hieronim Jakubowski
Keyword(s):  
Vascular Disease ◽  
Vascular System ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Autoimmune Response ◽  
Protein Targets ◽  
Homocysteine Thiolactone ◽  
Lysine Residues ◽  
Isopeptide Bonds ◽  
Chronic Activation

AbstractAccumulating evidence suggests that a metabolite of homocysteine (Hcy), the thioester Hcy-thiolactone, plays an important role in atherogenesis and thrombosis. Hcy-thiolactone levels are elevated in hyperhomocysteinemic humans and mice. The thioester chemistry of Hcy-thiolactone underlies its ability to form isopeptide bonds with protein lysine residues, which impairs or alters the protein's function. Protein targets for the modification by Hcy-thiolactone in human blood include fibrinogen, low-density lipoprotein, and high-density lipoprotein. Protein N-homocysteinylation leads to pathophysiological responses, including increased susceptibility to thrombogenesis caused by N-Hcy-fibrinogen, and an autoimmune response elicited by N-Hcy-proteins. Chronic activation of these responses in hyperhomocysteinemia over many years could lead to vascular disease. This article reviews recent evidence supporting the hypothesis that Hcy-thiolactone contributes to pathophysiological effects of Hcy on the vascular system.Clin Chem Lab Med 2007;45:1704–16.

Variation in Human Erythrocyte Membrane Unsaturated Fatty Acids: Correlation With Cardiovascular Disease

2010 ◽  
Vol 134 (1) ◽  
pp. 73-80
Author(s):  
Jorge L. Sepulveda ◽  
Yvette C. Tanhehco ◽  
Monica Frey ◽  
Lida Guo ◽  
Lorna J. Cropcho ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Vascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Fa Composition ◽  
Wide Range ◽  
Trans Fa ◽  
Cis And Trans

Abstract Context.—Whether cell membrane fatty acid (FA) composition is a useful indicator of vascular disease is unclear. Objective.—To study variation of erythrocyte (RBC) membrane FA in samples from healthy volunteers, hospitalized patients, and cardiac troponin I–elevated patients with myocardial damage without a priori assumptions as to FA composition. Design.—We separated FAs extracted from RBCs by gas chromatography and identified them by mass spectrometry. Fatty acids with abundance greater than 1% of total were quantified and compared: hexadecanoic (C16:0), octadecadienoic (C18:2), cis- and trans-octadecenoic (C18:1), and eicosatetraenoic (C20:4) acids. Deuterated standards established proportionality of FA recovery. The cis- and trans-C18:1 identification was verified by comparison with standards. Results.—In troponin-positive samples, C18:2 to C18:1 ratios were increased 30% compared with healthy controls or with random patient samples. Erythrocyte trans-C18:1 had a wide variation, ∼10-fold, in all groups but without differences between groups. Replicates showed that the wide range of RBC trans-FA load is not due to analytic variation. In healthy subjects, the RBC content of lower– molecular weight FAs (C16-C18) correlated with serum low-density lipoprotein cholesterol, but despite the established relationship between dietary trans-FA and increased low-density lipoprotein cholesterol, lipid profiles had no correlation with RBC trans-FA content. Conclusions.—Erythrocyte accumulation of unsaturated FA may be a useful indicator of vascular disease, whereas the wide range in trans-FAs suggests that both diet and genetic variation affect RBC trans-FA accumulation. Unsaturated FAs increase membrane fluidity and may reflect a natural response to subclinical vascular changes, which may in turn reflect increased risk of clinical disease.

Characterization of the adduct formed from the reaction between homocysteine thiolactone and low-density lipoprotein: antioxidant implications

1999 ◽  
Vol 26 (7-8) ◽  
pp. 968-977 ◽  
Author(s):  
Eric Ferguson ◽  
Neil Hogg ◽  
William E. Antholine ◽  
Joy Joseph ◽  
Ravinder Jit Singh ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Homocysteine Thiolactone

scholarly journals Cholesterol: A new game player accelerating endothelial injuries caused by SARS-CoV-2?

2020 ◽  
Author(s):  
Xiaoling Cao ◽  
Rong Yin ◽  
Helmut Albrecht ◽  
Daping Fan ◽  
Wenbin Tan
Keyword(s):  
Disease Severity ◽  
Vascular System ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Functional Impairments ◽  
Multiple Organs ◽  
Obesity And Diabetes ◽  
Global Threat ◽  
Kidney Liver ◽  
Pathophysiologic Mechanisms

The pandemic of coronavirus disease 2019 (COVID-19) has become a global threat to public health. Functional impairments in multiple organs have been reported in COVID-19 including lungs, heart, kidney, liver, brain and vascular system. Patients with metabolic-associated preconditions such as hypertension, obesity and diabetes are susceptible to experience severe symptoms. The recent emerging evidence of coagulation disorders in COVID-19 suggests that vasculopathy appears to be an independent risk factor promoting disease severity and mortality of affected patients. We have recently found that the decreased levels of low-density lipoprotein cholesterols (LDL-c) correlate with disease severity in COVID-19 patients, indicating pathological interactions between dyslipidemia and vasculopothy in COVID-19 patients. However, this clinical manifestation has been unintentionally underestimated by physicians and scientific communities. As metabolic-associated morbidities are generally accompanied with endothelial cell (EC) dysfunctions, these pre-existing conditions may make ECs more vulnerable to SARS-CoV-2 attack. In this mini-review, we summarize the metabolic and vascular manifestations of COVID-19 with an emphasis on the association between changes in LDL-c levels and the development of severe symptoms as well as the pathophysiologic mechanisms underlying the synergistic effect of LDL-c and SARS-CoV-2 on EC injuries and vasculopathy.

scholarly journals The LOX-1 Scavenger Receptor and Its Implications in the Treatment of Vascular Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
M. W Twigg ◽  
K. Freestone ◽  
S. Homer-Vanniasinkam ◽  
S. Ponnambalam
Keyword(s):  
Vascular Disease ◽  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Transgenic Animal ◽  
Lymphoid Cells ◽  
Scavenger Receptors ◽  
Model Studies ◽  
Arterial Blood ◽  
Oxidised Low Density Lipoprotein

Cardiovascular disease is the leading cause of death. The disease is due to atherosclerosis which is characterized by lipid and fat accumulation in arterial blood vessel walls. A key causative event is the accumulation of oxidised low density lipoprotein particles within vascular cells, and this is mediated by scavenger receptors. One such molecule is the LOX-1 scavenger receptor that is expressed on endothelial, vascular smooth muscle, and lymphoid cells including macrophages. LOX-1 interaction with OxLDL particles stimulates atherosclerosis. LOX-1 mediates OxLDL endocytosis via a clathrin-independent internalization pathway. Transgenic animal model studies show that LOX-1 plays a significant role in atherosclerotic plaque initiation and progression. Administration of LOX-1 antibodies in cellular and animal models suggest that such intervention inhibits atherosclerosis. Antiatherogenic strategies that target LOX-1 function using gene therapy or small molecule inhibitors would be new ways to address the increasing incidence of vascular disease in many countries.

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