Disease ⇒ Atherosclerosis {40000106}

Shared Reference Notes

• [1.1] 
  - Human blood platelets are a critical contributor to the hemostatic process and a crucial role in developing atherosclerosis and, finally, contribute to cardiac events. - Gut microbiota and their metabolites play an important role in systemic inflammation and modulate various CVD risk factors.
• [1.2] 
  - Distinct members of the order Burkholderiales were present at high levels in all atherosclerotic plaques obtained from patients with atherosclerosis with the genus Curvibacter being predominant in all plaque samples. Moreover, unclassified Burkholderiales as well as members of the genera Propionibacterium and Ralstonia were typically the most significant taxa for all atherosclerotic plaques.
• [1.3] 
  - Aortic atherosclerotic lesions were significantly reduced after F. nucleatum infection suggesting a potential protective function for this member of the oral microbiota.
• [1.4] 
  -Clostridia (sensu stricto), bifidobacteria, and coriobacteria were significantly correlated with TMA production in the mixed fermentation system but did not produce notable quantities of TMA from TMAO in pure culture. - TMAO stimulated the growth of Enterobacteriaceae; these bacteria produced most TMA from TMAO. - Reduction of TMAO by the gut microbiota (predominantly Enterobacteriaceae) to TMA followed by host uptake of TMA into the bloodstream from the intestine and its conversion back to TMAO by host hepatic enzymes is an example of metabolic retroconversion. TMAO influences microbial metabolism depending on isolation source and taxon of gut bacterium.
• [1.5] 
  - the abundance of #Roseburia intestinalis is negatively correlated with the size of atherosclerotic lesions in the mouse model of atherosclerosis. - when #Roseburia intestinalis was taken along with a high-fiber diet, aortic atherosclerotic plaques were reduced in size. This study suggests that the butyrate, a microbial metabolite, mediates these effects
• [1.6] [#Coronary artery disease] 
  - #Bilophila, a genus of gut microbes, can metabolize #TMA, resulting in lower #TMAO, suggesting that differences in #TMA-metabolizing gut bacteria in individuals lead to different ultimate effects, and replacement of relevant bacteria may reduce the risk from #TMAO.
• - #Butyrate has been shown to be a potential therapeutic strategy for atherosclerosis, specifically by its promoting cholesterol efflux through upregulation of ABCA1 expression in macrophages, thereby ameliorating atherosclerosis.
• [#Para-cresol] - #TMAO is the hepatic oxidation product of the microbial trimethylamine (#TMA). - dietary supplementation with #TMAO was shown to promote atherogenesis and development of atherosclerosis in mice. - #TMAO levels associate with an increased risk of adverse cardiovascular events. - Carotid atherosclerosis was demonstrated to be associated with gut microbial metabolites (especially #TMAO and p-cresol sulfate) in >3,000 patients, which could serve as an independent predictor of the disease.
• [1.7] [#Serine-glycine] 
  - Intraperitoneal administration of L654 over 7 weeks to HFD-fed Ldlr−/− mice resulted in hypocholesterolemic effects and significantly attenuated the progression of atherosclerosis. - L654 and other bacterial glycine lipids in feces, liver, and serum were markedly reduced alongside changes in #Bacteroidetes relative abundance in HFD-fed mice.
• [1.8] 
  - NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome and gut microbiota are closely related to the occurrence and development of AS
• [1.9] [#Hearth attack] [#Carnitine, #Crotonobetaine, #TMAO, #γ-butyrobetaine] [#Meat-based diet] 
• - In a mouse model, it was demonstrated that #Methanobrevibacter smithii, #Methanosarcina mazei, and #Methanomicrococcus blatticola use #TMA as growth substrates, resulting in reduced atherosclerosis
• [1.11] 
  - Trimethylamine (#TMA) is generated by the gut microbiome and in the host converted by flavin-containing monooxygenase (FMO3) into trimethylamine N-oxide (#TMAO), which has been implicated in chronic cardiovascular and metabolic diseases. - Using cell culture systems and patient biopsies > #TMAO reprograms skin fibroblasts, vascular endothelial cells, and adipocytic progenitor cells into myofibroblasts via the putative #TMAO receptor protein R-like endoplasmic reticulum kinase (PERK). - FMO3 was detected in skin fibroblasts and its expression stimulated by TGF-β1. - FMO3 was elevated in #Systemic sclerosis skin biopsies and in #Systemic sclerosis fibroblasts.
• [1.12] [#End-stage renal disease] 
  - #TMAO is a major risk factor for cardiovascular disease, renal fibrosis and functional impairment, atherosclerosis, and #Colorectal cancer.
• [1.13] [#CVD] 
  - gut microbiota-dependent metabolism of dietary #Phenylalanine into #Phenylacetic acid (PAA) is critical in #Phenylacetylglutamine (PAGln) production, a metabolite linked to atherosclerotic cardiovascular disease (ASCVD). - PPFOR is the main contributor for PAA production in #Bacteroides thetaiotaomicron. - PPDC plays an important role in PAA generation in #Proteus mirabilis. - PPFOR and PPDC contribute to PAA production and PAGln formation in colonized hosts. - Gut microbial ppdc and ppfor homolog abundances are each associated with ASCVD in humans.
• [1.14] [#CVD] [#Campylobacter rectus, #Porphyromonas endodontalis, #Porphyromonas gingivalis, #Prevotella intermedia, #Prevotella nigrescens] 
  - 23 oral commensal bacteria, either individually or in coexistence, within carotid endarterectomy biopsies from patients undergoing surgical procedures. Of these 23 bacteria, five were unique to coronary plaques, including P. gingivalis, P. endodontalis, P. intermedia, C. rectus, and P. nigrescens.
• [1.15] [#Diabetes Type 2, #Irritable bowel syndrome] 
  - Increased levels of #Ceramides were reported in mucosal samples from IBS patients as well as in plasma and tissue samples in diabetes, cardiomyopathy, insulin resistance, atherosclerosis and #Steatohepatitis.
• [1.16] 
  - Species belonging to #Sellimonas have been reported to be increased in inflammatory diseases including #Ankylosing spondylitis, atherosclerosis and liver #Cirrhosis
• - #Ruminococcusgauvreauii belongs to the family Ruminococcaceae and at species level was found to be increased in atherosclerotic conditions. - #Depression is known to be causally associated with atherosclerosis.
• [1.17] [#CVD] [#Lipopolysaccharide, #TMA, #TMAO] 
• [1.18] [#Gingipains] 
  - #Porphyromonas gingivalis is a major pathogenic bacterium involved in the pathogenesis of periodontitis. Citrullination has been reported as the underlying mechanism of the pathogenesis, which relies on the interplay between two virulence factors of the bacterium, namely gingipain R and the bacterial peptidyl arginine deiminase. - Gingipain R cleaves host proteins to expose the C-terminal arginines for peptidyl arginine deiminase to citrullinate and generate #Citrullinated Proteins. - Citrullinating proteins present in the host synovial tissues, atherosclerotic plaques and neurons. - both virulence factors are the key factors that trigger distal effects mediated by citrullination, leading to the development of some non-communicable diseases, such as #Rheumatoid Arthritis, atherosclerosis, and #Alzheimer’s disease.
• [1.19] 
  - Four basic pathogenic mechanisms have been proposed to explain the relationship between oral inflammations and atherosclerosis. - (1) Colonisation of arterial walls and atherosclerotic plaques by dental bacteria that enter the bloodstream. - (2) Increase in systemic inflammation owing to the presence of an oral infection. Inflammatory elements released from sites of oral infections can be transported from the mouth to the atherosclerotic plaques via blood flow, thus increasing the risk of plaque rupture. - (3) Activation of the host immune response to specific components of oral pathogens, thus causing autoimmunity to host proteins. - (4) Pro-atherogenic effects resulting from specific bacterial toxins released by oral pathogenic bacteri
• [#Chronic periodontitis, #Periodontal abscess] - periodontopathogens can be disseminated through the blood flow to other body parts where they may enhance inflammatory processes that can lead to the development or exacerbation of atherosclerosis.
• [#Rheumatic Hearth Disease] [#Porphyromonas gingivalis] - Oral microbes, including P. gingivalis, #Actinomyces, #Streptococcus, and #Treponema denticola, have been confirmed as sources of infected heart valves, atherosclerotic plaques, and rheumatic heart valves
• - the existence of #Veillonella and #Streptococcus in atherosclerotic plaques, whose bacterial abundances positively correlated with their abundance in the oral cavity, indicating that oral #Veillonella probably spread to extraoral organs via the circulatory system
• [1.21] [#Diabetes Type 2] 
  - genus Actinobacterium #Collinsella was confirmed to be associated with #Alzheimer’s disease, as well as #Rheumatoid Arthritis, atherosclerosis, and type 2 diabetes.
• [1.22] [#CVD] [#Streptococcus] 
  - CACS-associated species was negatively associated with the microbially derived #Tryptophan metabolite #Indole #Propionate, a metabolite that has been found inversely associated with atherosclerotic coronary disease in humans and reduced progression of atherosclerosis in mice.
• [#Streptococcus agalactiae, #Streptococcus anginosus, #Streptococcus gordonii, #Streptococcus oralis, #Streptococcus parasanguinis] - S. anginosus, S. oralis subsp oralis, S. parasanguinis, S. gordonii, and S. agalactiae were associated with coronary atherosclerosis. - These species all belong to the viridans group streptococci (VGS), except for S. agalactiae (a β-hemolytic non-VGS). - VGS can enter the bloodstream through mucosal barrier injuries from daily dental care activities and dental procedures, and could also pass the gut barrier when injured. - VGS can invade human aortic endothelial cells and stimulate atherosclerosis-related proinflammatory cytokines
• - The #Streptococcus genus was associated with coronary artery calcium score (CACS)
• [#Streptococcus] - genes related to anaerobic fermentation of fatty acids were associated with CACS-associated species
• - oral bacteria such as #Veillonella spp and #Streptococcus spp found in the oral cavity, fecal samples, and carotid atherosclerotic plaque.9 Given the association between dental health and endothelial dysfunction and atherosclerotic disease,
• [#Streptococcus] - issimilatory #Nitrate reduction > CACS-associated species > converts #Nitrate to #Ammonia, and having an increased activity of this pathway in the colon could potentially inhibit the potential positive cardiovascular effects of #Nitrate.
• [#Streptococcus] [#Smoking] - Several tobacco metabolites (ie, 3-hydroxycotinine glucuronide, cotinine N-oxide, and norcotinine) were positively associated with species positively associated with CACS and negatively associated with species negatively associated withcoronary artery calcium score (CACS).
• [1.23] [#Ulcerative Colitis] [#Desulfovibrio desulfuricans] 
  - Barrier dysfunction in the intestine is a pathogenic factor in D. desulfuricans-induced UC, and endothelial dysfunction promotes atherosclerosis.
• - Some specific gut microbes, such as #Akkermansia muciniphila, #Bacteroides vulgatus, #Bacteroides dorei, and #Roseburia intestinalis are associated with the development of atherosclerosis.
• [#Lipopolysaccharide] - TLR4 is a pattern-recognizing receptor that recognizes exogenous ligands, such as bacterial LPS. - activation of TLR4 by LPS induces the activation of NF-κB and mitogen-activated protein kinase (MAPK) pathways and ultimately elicits the release of proinflammatory cytokines. - The activation of TLR4 is a key etiological condition for the development of atherosclerosis.
• [1.24] 
  - #Sutterella wadsworthensis was associated with 2 Vascular stifness measures, AIX and PWV. - Other examples of ASVs associated with Vascular stifness were #Collinsella aerofaciens.
• [1.25] [#Heat shock proteins] 
  - HSPs function as an immunomodulator, promoting the production of cytokines or transmitting receptor-mediated signals to other cells. - #Hypertension, a risk factor for atherosclerosis, has been shown in studies to increase HSP secretion from macrophages, smooth muscle cells, and endothelial cells.
• - #TMAO has been shown to promote the formation of atherosclerosis in murine macrophages by upregulating the scavenger receptor (SR), increasing the expression of #Heat shock proteins (HSPs), proinflammatory cytokines, and plasma #Cholesterol levels
• [1.26] [#Preeclamsia] 
  - PE have been observed to exhibit “atherosclerosis-like” lesions in the spiral arteries of their placentas, accompanied by lipid accumulation. - rats model > TMAO-induced reactive oxygen species in remodeling spiral arterial defects in the placenta, which may contribute to the onset of PE
• [1.27] [#Tannerella forsythia] 
  - T. forsythia is orally inoculated in ApoEnull mice, it results in increased serum #Amyloid A, decreased serum #Nitric Oxide, and elevated serum lipoproteins > increase in total plasma cholesterol levels.
• [1.28] [#Glycine amidinotransferase] [#Walnut] 
  - GATM gene correlate with plasma #Homoarginine concentrations and greater cellular GATM expression in vitro is associated with increased homoarginine. - Low serum #Homoarginine is an independent biomarker for increased risk of adverse cardiovascular events and all-cause mortality. - #Homoarginine supplementation reduces atherosclerotic plaque development via modulation of the adaptive immune system
• [1.29] [#Lactococcus lactis] 
  - oral administration of L. lactis strain NZ3900 pre-stimulated with #Nisin significantly limited the formation of a fatty liver phenotype and the progression of early atherosclerosis in a rabbit model fed a high #Cholesterol diet.
• [1.31] [#Quinolinic acid] [#High Fat Diet] 
  - QA inhibits the increase of #Cholesterol, #TMA, #TMAO, CXCL13, TIMP-1 and HMGB1 levels in peripheral blood of Apoe−/− mice induced by HFD, suggesting that QA can effectively inhibit HFD-induced atherosclerosis.
• - #Arbutin improved intestinal development and inhibited serum lipid level in mice by increasing the #Lactobacillus intestinalis abundance
• [#Quinolinic acid] [#High Fat Diet] - HFD induced weight gain and aortic tissue atherogenesis in Apoe−/− mice, but was inhibited by QA or low-frequency ABX treatment.
• [1.32] [#High temperature and humidity] 
  HTH > elevated plasma #TMAO, which are transformed from #Choline by specific bacterial genera, and associated with high atherosclerosis burden
• [1.33] 
  - #Bifidobacterium bifidum is considered to have a protective effect on the cardiovascular system, and many studies have shown that it can lower human blood #Cholesterol levels, thus reducing the risk of atherosclerosis
• [1.34] 
  - Depletion of Bacteroides xylanisolvens, Odoribacter splanchnicus, Eubacterium eligens, Roseburia inulinivorans, and Roseburia intestinalis. - At the functional level, healthy metagenomes were both enriched in pathways of starch degradation V, glycolysis III (from glucose), CDP‐diacylglycerol biosynthesis, and folate transformations. - R inulinivorans and R intestinalis are major contributors to starch degradation V. - E eligens greatly contribute to the pathway CDP‐diacylglycerol biosynthesis. - B xylanisolvens and B uniformis contribute to folate transformations II. - Two gut microbial metabolites, nicotinic acid and hydrocinnamic acid, had significantly higher predicted abundance in the control samples compared to the patients in the Chinese cohort, and interestinglynicotinic acid is already an effective lipid‐lowering drug to reducing cardiovascular risk.
• [1.35] 
  - The gut microbiota composition of patients with atherosclerosis (AS) contains relatively high levels of Collinsella.

References Notes