Vaccination against atherosclerosis.
Ontology highlight
ABSTRACT:
SUBMITTER: Kobiyama K
PROVIDER: S-EPMC6765450 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
Publications
Vaccination against atherosclerosis.
Kobiyama Kouji K Saigusa Ryosuke R Ley Klaus K
Current opinion in immunology 20190329
Atherosclerosis is a chronic inflammatory disease that causes most heart attacks and strokes, making it the biggest killer in the world. Although cholesterol-lowering drugs have dramatically reduced these major adverse cardiovascular events, there remains a high residual risk called inflammatory risk. Atherosclerosis has an autoimmune component that can be manipulated by immunologic approaches including vaccination. Vaccination is attractive, because it is antigen-specific, does not impair host ...[more]
Similar Datasets
Project description:Patients with advanced microsatellite unstable (MSI-H) colorectal cancer will be vaccinated with three so called frame shift peptides (FSPs), AIM2(-1), HT001(-1) and TAF1B(-1) combined with Montanide ISA-51 VG. By this, an immune response directed against MSI-induced FSPs that are shared by the majority of MSI-H colorectal cancers can be induced. The aim is to show that vaccination against MSI-induced FSPs is safe and can induce or enhance immune responses against MSI-H colorectal cancer-associated antigens.
| 2114862 | ecrin-mdr-crc
Project description:Vaccination against Shigella and ETEC
| PRJEB5149 | ENA
Project description:BACKGROUND:Understanding reasons for and against vaccination from the parental perspective is critical for designing vaccination campaigns and informing other interventions to increase vaccination uptake in Canada. The objective of this study was to understand maternal vaccination decision making for children. METHODS:Mothers participating in a longitudinal community-based pregnancy cohort, the All Our Babies study in Calgary, Alberta, completed open-ended survey questions providing explanations for the vaccination status of their child by 24?months postpartum. Qualitative responses were linked to administrative vaccination records to examine survey responses and recorded child vaccination status. RESULTS:There were 1560 open-ended responses available; 89% (n?=?1391) provided explanations for vaccinating their children, 5% (n?=?79) provided explanations for not vaccinating/delaying, and 6% (n?=?90) provided explanations for both. Themes were similar for those vaccinating and not vaccinating/delaying; however, interpretations were different. Two broad themes were identified: Sources of influence and Deliberative Processes. Sources of influence on decision making included personal, family, and external experiences. Deliberative Processes included risk, research, effectiveness, and balancing risks/benefits. Under Deliberative Processes, responsibility was a category for those vaccinating; while choice, instrumental/practical, and health issues were categories for those not vaccinating/delaying. Mothers' levels of conviction and motivation provided a Context for understanding their decision making perspectives. CONCLUSIONS:Vaccination decision making is complex and impacted by many factors that are similar but contribute to different decisions depending on mothers' perspectives. The results of this study indicate the need to examine new intervention approaches to increase uptake that recognize and address feelings of pressure and parental commitment to choice.
| S-EPMC6327385 | biostudies-other
Project description:Objective- Inflammatory stimuli enhance the progression of atherosclerotic disease. Inflammation also increases the expression of hepcidin, a hormonal regulator of iron homeostasis, which decreases intestinal iron absorption, reduces serum iron levels and traps iron within macrophages. The role of macrophage iron in the development of atherosclerosis remains incompletely understood. The objective of this study was to investigate the effects of hepcidin deficiency and decreased macrophage iron on the development of atherosclerosis. Approach and Results- Hepcidin- and LDL (low-density lipoprotein) receptor-deficient ( Hamp-/-/ Ldlr-/-) mice and Hamp+/+/ Ldlr-/- control mice were fed a high-fat diet for 21 weeks. Compared with control mice, Hamp-/-/ Ldlr-/- mice had decreased aortic macrophage activity and atherosclerosis. Because hepcidin deficiency is associated with both increased serum iron and decreased macrophage iron, the possibility that increased serum iron was responsible for decreased atherosclerosis in Hamp-/-/ Ldlr-/- mice was considered. Hamp+/+/ Ldlr-/- mice were treated with iron dextran so as to produce a 2-fold increase in serum iron. Increased serum iron did not decrease atherosclerosis in Hamp+/+/ Ldlr-/- mice. Aortic macrophages from Hamp-/-/ Ldlr-/- mice had less labile free iron and exhibited a reduced proinflammatory (M1) phenotype compared with macrophages from Hamp+/+/ Ldlr-/- mice. THP1 human macrophages treated with an iron chelator were used to model hepcidin deficiency in vitro. Treatment with an iron chelator reduced LPS (lipopolysaccharide)-induced M1 phenotypic expression and decreased uptake of oxidized LDL. Conclusions- In summary, in a hyperlipidemic mouse model, hepcidin deficiency was associated with decreased macrophage iron, a reduced aortic macrophage inflammatory phenotype and protection from atherosclerosis. The results indicate that decreasing hepcidin activity, with the resulting decrease in macrophage iron, may prove to be a novel strategy for the treatment of atherosclerosis.
| S-EPMC6344241 | biostudies-literature
Project description:Conjugate vaccines protect vaccinated individuals against both disease from and nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae. Protection is specific to the capsular serotype(s) included in the vaccine. This specificity has raised concern that vaccination against particular ("targeted") serotypes may cause an increase in carriage of (and diseases attributable to) nontargeted serotypes. I analyzed a mathematical model designed to predict the factors affecting, and the expected extent of, such replacement in the host population. The conditions for competitive exclusion and coexistence of serotypes under mass vaccination are derived, and the equilibrium carriage of target and nontarget serotypes is determined under various ecological and epidemiological conditions. The eradication threshold for a target serotype in the presence of competing, nontarget serotypes is always lower for serotype-specific than for bivalent vaccines. In a two-serotype model, the increase in the prevalence of any single nontargeted serotype due to vaccination will not exceed the total reduction in prevalence of a targeted serotype. However, if three or more serotypes interact epidemiologically, vaccination against one type may increase carriage of a second more than it decreases carriage of the first. Carriage of a second serotype against which the vaccine offers only partial protection may initially increase and then decrease as a function of vaccine coverage. I discuss the extent to which these theoretical results can account for existing data on serotype replacement after vaccination against H. influenzae and their implications for vaccine policy.
| S-EPMC21091 | biostudies-other
Project description:Obesity endangers the lives of millions of people worldwide, through comorbidities such as heart disease, cancers, type 2 diabetes, stroke, arthritis, and major depression. New approaches to control body weight remain a high priority. Vaccines traditionally have been used to protect against infectious diseases and, more recently, for unconventional targets such as drug addiction. Methodologies that could specifically modulate the bioavailability of an endogenous molecule that regulates energy balance might provide a new foundation for treating obesity. Here we show that active vaccination of mature rats with ghrelin immunoconjugates decreases feed efficiency, relative adiposity, and body weight gain in relation to the immune response elicited against ghrelin in its active, acylated form. Three active vaccines based on the 28-aa residue sequence of ghrelin, a gastric endocrine hormone, were used to immunize adult male Wistar rats (n = 17). Synthetic ghrelin analogs were prepared that spanned residues 1-10 [ghrelin (1-10) Ser-3(butanoyl) hapten, Ghr1], 13-28 [ghrelin (13-28) hapten, Ghr2], and 1-28 [ghrelin(1-28) Ser-3(butanoyl) hapten, Ghr3], and included n-butanoyl esters at Ser-3. Groups immunized with Ghr1 or Ghr3 showed greater and more selective plasma binding capacity for the active, Ser-3-(n-octanoyl) form of ghrelin as compared with Ghr2 or keyhole limpet hemocyanin vaccinated controls. Accordingly, they gained less body weight, with sparing of lean mass and preferential reduction of body fat, consistent with reduced circulating leptin levels. The ratio of brain/serum ghrelin levels was lower in rats with strong anti-ghrelin immune responses. Effects were not attributable to nonspecific inflammatory responses. Vaccination against the endogenous hormone ghrelin can slow weight gain in rats by decreasing feed efficiency.
| S-EPMC1559781 | biostudies-literature
Project description:Blood vessels are continually exposed to circulating lipids and elevations of ApoB containing lipoproteins cause atherosclerosis. Lipoprotein metabolism is highly regulated by lipolysis, largely at the level of the capillary endothelium lining metabolically active tissues. How large blood vessels, the site of atherosclerotic vascular disease, regulate the flux of fatty acids (FA) into triglyceride (TG) rich lipid droplets (LD) is not known. Here, we show that deletion of the enzyme, adipose triglyceride lipase (ATGL) in the endothelium, leads to neutral lipid accumulation in vessels and impairs endothelial dependent vascular tone and nitric oxide synthesis to promote endothelial dysfunction. Mechanistically, the loss of ATGL leads to endoplasmic reticulum stress-induced inflammation, thereby promoting EC dysfunction. Consistent with this mechanism, deletion of endothelial ATGL markedly increases lesion size in a model of atherosclerosis. Together, these data demonstrate that the dynamics of FA flux through LD impacts EC homeostasis and consequently large vessel function during normal physiology and in a chronic disease state
2023-10-31 | GSE246138 | GEO
Project description:Blood vessels are continually exposed to circulating lipids and elevations of ApoB containing lipoproteins cause atherosclerosis. Lipoprotein metabolism is highly regulated by lipolysis, largely at the level of the capillary endothelium lining metabolically active tissues. How large blood vessels, the site of atherosclerotic vascular disease, regulate the flux of fatty acids (FA) into triglyceride (TG) rich lipid droplets (LD) is not known. Here, we show that deletion of the enzyme, adipose triglyceride lipase (ATGL) in the endothelium, leads to neutral lipid accumulation in vessels and impairs endothelial dependent vascular tone and nitric oxide synthesis to promote endothelial dysfunction. Mechanistically, the loss of ATGL leads to endoplasmic reticulum stress-induced inflammation, thereby promoting EC dysfunction. Consistent with this mechanism, deletion of endothelial ATGL markedly increases lesion size in a model of atherosclerosis. Together, these data demonstrate that the dynamics of FA flux through LD impacts EC homeostasis and consequently large vessel function during normal physiology and in a chronic disease state
2023-12-07 | GSE246083 | GEO
Project description:Cholesterol biosynthetic intermediates such as lanosterol and desmosterol are emergent immune regulators of macrophages in response to inflammatory stimuli or lipid overloading, respectively. However, the participation of these sterols in regulating macrophage functions in the physiological context of atherosclerosis, an inflammatory disease driven by the accumulation of cholesterol-laden macrophages in the artery wall, has remained elusive. Here we report that desmosterol, the most abundant cholesterol biosynthetic intermediate in human coronary artery lesions, plays an essential role during atherogenesis, serving as a key molecule integrating cholesterol homeostasis and immune responses in macrophages. Depletion of desmosterol in myeloid cells by overexpression of 3β-hydroxysterol Δ24-reductase (DHCR24), the enzyme that catalyzes conversion of desmosterol to cholesterol, promotes the progression of atherosclerosis. Single cell transcriptomics in isolated CD45+CD11b+ cells from atherosclerotic plaques demonstrate that depletion of desmosterol increases interferon (IFN) responses and attenuates the expression of anti-inflammatory macrophage markers. Lipidomic and transcriptomic analysis of in vivo macrophage foam cells demonstrate that desmosterol is a major endogenous liver X receptor (LXR) ligand involved in LXR/RXR activation and thus, macrophage foam cell formation. Decreased desmosterol accumulation in mitochondria promotes macrophage mito-ROS production and NLRP3-dependent inflammasome activation. Deficiency of NLRP3 or ASC rescues the increased inflammasome activity and atherogenesis observed in desmosterol-depleted macrophages. Altogether, these findings underscore the critical function of desmosterol in the atherosclerotic plaque to dampen inflammation, by integrating with macrophage cholesterol metabolism and inflammatory activation, and protecting from disease progression.
2021-12-31 | GSE172374 | GEO
Project description:In Italy, the introduction of Universal Varicella Vaccination (UVV) has been decided but postponed, as a national programme, until 2015, when data from Regions which have already implemented it will be available. Starting from 2003, eight Italian Regions (Basilicata, Calabria, Friuli Venezia Giulia, Apulia, Sardinia, Sicily, Tuscany and Veneto) have progressively introduced UVV, in their immunization programme, with different schedules in children aged 13-15 months and 5-6 years, currently a two-dose schedule is adopted by all Regions. In June 2013, an Interregional Group on Varicella Vaccination (IGVV) has been established in order to assess the effectiveness of varicella vaccination with standardized and shared tools. The aim of this study was to evaluate the impact of varicella vaccination on the incidence and hospitalizations due to varicella and its complications in the period 2003-2012 in order to support the Italian decision makers on the future national adoption. Preliminary data showed that a general reduction of incidence and hospitalization rates was observed in the study period, resulting in relevant savings for the National Health Service. Immunization coverage with first dose at 24 months of age was high in all Regions (84%-95%) in 2012. Adverse events due to varicella vaccines were rare and without permanent sequelae. Underreporting of varicella cases and delays in the administration of the first dose of varicella vaccines were the main critical issues. In conclusion, solid evidences in support of universal UVV arise from the experiences available today in Italy.
| S-EPMC4514224 | biostudies-other