NIH-supported researchers find link between allergen in red meat and heart disease | National Institutes of Health (NIH)

Only in recent years did scientists identify the main allergen in red
meat, called galactose-α-1,3-galactose, or alpha-Gal, a type of complex
sugar. They also found that a tick — the Lone Star tick — sensitizes
people to this allergen when it bites them. That is why red meat
allergies tend to be more common where these ticks are more prevalent,
such as the Southeastern United States, but also extending to other
areas, including Long Island, New York.


Researchers have suspected for some time that allergens can trigger
certain immunological changes that might be associated with plaque
buildup and artery blockages, but no one had identified a specific
substance that is responsible for this effect. In the current study,
researchers showed for the first time that a specific blood marker for
red meat allergy was associated with higher levels of arterial plaque,
or fatty deposits on the inner lining of the arteries. The blood marker
they identified is a type of antibody (immunoglobulin or IgE) that is
specific to the alpha-Gal allergen.

Gum disease opens up the body to a host of infections | Science News

When Salomon Amar, a periodontal specialist at Boston University, began exploring links between oral bacteria and heart disease in animal studies in the late 1990s, reactions were lukewarm. “Many cardiologists thought we were a bit crazy,” he says. Skepticism still abounds, but the same molecular tools that have dramatically changed understanding of the gut microbiome are now allowing scientists to track and examine bacteria in the mouth. Advocates of a connection between the artery disease atherosclerosis and microbes are hoping to find convincing proof of their suspicions, while exploring links between ailing gums and other conditions, including cancer, arthritis, diabetes and even Alzheimer’s disease.

Exposure to nanoparticles may threaten heart health -- ScienceDaily

Nanoparticles, extremely tiny particles measured in billionths of a meter, are increasingly everywhere, and especially in biomedical products. Their toxicity has been researched in general terms, but now a team of Israeli scientists has for the first time found that exposure nanoparticles (NPs) of silicon dioxide (SiO2) can play a major role in the development of cardiovascular diseases when the NP cross tissue and cellular barriers and also find their way into the circulatory system. Their study, published in the December issue of Environmental Toxicology.

In this study, researchers exposed cultured laboratory mouse cells resembling the arterial wall cells to NPs of silicon dioxide and investigated the effects. SiO2 NPs are toxic to and have significant adverse effects on macrophages. a type of white blood cell that take up lipids, leading to atherosclerotic lesion development and its consequent cardiovascular events, such as heart attack or stroke. Macrophages accumulation in the arterial wall under atherogenic conditions such as high cholesterol, triglycerides, oxidative stress -- are converted into lipids, or laden "foam cells" which, in turn, accelerate atherosclerosis development.

Genome wide expression changes in vascular tissue identified due to infection/diet

Although it has been shown that a diet high in fat and exposure to certain bacteria can cause atherosclerosis (the buildup of fats, cholesterol and other substances on artery walls which can restrict blood flow), researchers have for the first time identified distinct gene pathways that are altered by these different stimuli. These findings, which currently appear in BMC Genomics, suggest that future therapies for this disease may need to be individualized.

Transmission of Atherosclerosis Susceptibility with Gut Microbial Transplantation.

Recent studies indicate both clinical and mechanistic links between atherosclerotic heart disease and intestinal microbial metabolism of certain dietary nutrients producing trimethylamine N-oxide (TMAO). Here we test the hypothesis that gut microbial transplantation can transmit choline diet-induced TMAO production and atherosclerosis susceptibility. First, a strong association was noted between atherosclerotic plaque and plasma TMAO levels in a mouse diversity panel (n=22 strains, R=0.38; P=0.0001). An atherosclerosis-prone and high TMAO producing strain, C57BL/6J, and an atherosclerosis-resistant and low TMAO producing strain, NZW/LacJ, were selected as donors for cecal microbial transplantation into apolipoprotein e null mice in which resident intestinal microbes were first suppressed with antibiotics. TMA and TMAO levels were initially higher in recipients on choline diet that received cecal microbes from C57BL/6J inbred mice; however, durability of choline diet-dependent differences in TMA/TMAO levels was not maintained to the end of the study. Mice receiving C57BL/6J cecal microbes demonstrated choline diet-dependent enhancement in atherosclerotic plaque burden compared to recipients of NZW/LacJ microbes. Microbial DNA analyses in feces and cecum revealed transplantation of donor microbial community features into recipients with differences in taxa proportions between donor strains that were transmissible to recipients, and that tended to show coincident proportions with TMAO levels. Proportions of specific taxa were also identified that correlated with plasma TMAO levels in donors and recipients, and with atherosclerotic lesion area in recipients. Atherosclerosis susceptibility may be transmitted via transplantation of gut microbiota. Gut microbes may thus represent a novel therapeutic target for modulating atherosclerosis susceptibility.

Disturbance in blood flow leads to epigenetic changes, atherosclerosis -- ScienceDaily

Disturbed patterns of blood flow induce lasting epigenetic changes to genes in the cells that line blood vessels, and those changes contribute to atherosclerosis, researchers have found. The findings suggest why the protective effects of good blood flow patterns, which aerobic exercise promotes, can persist over time.

Atherosclerosis and Alzheimer - diseases with a common cause? Inflammation, oxysterols, vasculature.

Aging is accompanied by increasing vulnerability to pathologies such as atherosclerosis (ATH) and Alzheimer disease (AD). Are these different pathologies, or different presentations with a similar underlying pathoetiology? DISCUSSION:
Both ATH and AD involve inflammation, macrophage infiltration, and occlusion
of the vasculature. Allelic variants in common genes including APOE
predispose to both diseases. In both there is strong evidence of disease
association with viral and bacterial pathogens including herpes simplex
and Chlamydophila. Furthermore, ablation of components of the immune
system (or of bone marrow-derived macrophages alone) in animal models
restricts disease development in both cases, arguing that both are
accentuated by inflammatory/immune pathways. We discuss that amyloid
beta, a distinguishing feature of AD, also plays a key role in ATH.
Several drugs, at least in mouse models, are effective in preventing the
development of both ATH and AD. Given similar age-dependence, genetic
underpinnings, involvement of the vasculature, association with
infection, Abeta involvement, the central role of macrophages, and drug
overlap, we conclude that the two conditions reflect different
manifestations of a common pathoetiology.Mechanism: Infection and
inflammation selectively induce the expression of cholesterol
25-hydroxylase (CH25H). Acutely, the production of 'immunosterol'
25-hydroxycholesterol (25OHC) defends against enveloped viruses. We
present evidence that chronic macrophage CH25H upregulation leads to
catalyzed esterification of sterols via 25OHC-driven allosteric
activation of ACAT (acyl-CoA cholesterol acyltransferase/SOAT),
intracellular accumulation of cholesteryl esters and lipid droplets,
vascular occlusion, and overt disease.

SUMMARY: We postulate that AD and ATH are both caused by chronic immunologic challenge that induces CH25H expression and protection against
particular infectious agents, but at the expense of longer-term
pathology.

Related

Convergence of genes implicated in Alzheimer's disease on the cerebral cholesterol shuttle: APP, cholesterol, lipoproteins, and atherosclerosis

Pivotal role of NOD2 in inflammatory processes affecting atherosclerosis and periodontal bone loss

Apolipoprotein E^−/− (ApoE^−/−) mice deficient in nucleotide binding oligomerization domain-containing protein 2 (NOD2) and subjected to an oral gavage of Porphyromonas gingivalis developed elevated serum inflammatory cytokines, cholesterol, alveolar bone loss, and atherosclerosis. Stimulation of NOD2 by Muramyl DiPeptide (MDP) in ApoE^−/− mice reduced P. gingivalis-induced inflammatory cytokines, cholesterol, alveolar bone loss, and atherosclerosis by reducing the expression of inhibitor of NF-κB kinase-β, NF-κB, JNK mRNA, and TNF-α protein levels. A reduction in body weight gain was observed in ApoE^−/− mice fed a high-fat diet (HFD) and injected with MDP compared to ApoE^−/− mice fed a HFD but saline injected. MDP activation of NOD2 should be considered in the treatment of inflammatory processes affecting atherosclerosis, bone loss, and possibly, weight gain.

Nicotine drives cell invasion that contributes to plaque formation in coronary arteries

Nicotine, the major addictive substance in cigarette smoke, contributes to smokers' higher risk of developing atherosclerosis, the primary cause of heart attacks, according to research to be presented at the American Society for Cell Biology Annual Meeting in New Orleans.These findings suggest that e-cigarettes, the battery-powered devices that deliver nicotine in steam without the carcinogenic agents of tobacco smoke, may not significantly reduce smokers' risk for heart disease, said Chi-Ming Hai, Ph.D., of Brown University.

Bacterial DNA signatures in carotid atherosclerosis represent both commensals and pathogens of skin origin.

Infectious agents have been suggested to be involved in atherosclerosis. By using a novel subtraction broad-range PCR approach, we defined bacterial DNA signatures in surgically removed sterile carotid artery endarterectomy plaques of patients with carotid atherosclerosis. Eighty partial bacterial 16S rDNA nucleotide sequences from eight patients were studied. Furthermore, 34 clones representing 21 bacterial sequence-types from the reagents used for DNA extraction and PCR amplification were determined. After subtraction of these potential methodological contaminants, 23 bacterial sequence-types were considered as clinically relevant findings. The most prominent phylum, Actinobacteria, accounted for 74% of these relevant sequences. Furthermore, according to the Human Microbiome project database, interestingly, nearly all (94%) of the sequences were associated with the human skin microbiome.

Related articles

• Ascitic Microbiota Composition Is Correlated with Clinical Severity in Cirrhosis with Portal Hypertension
• The silent bacteria and atherosclerosis

Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis : Nature Medicine

Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). We demonstrate here that metabolism by intestinal microbiota of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice. Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed. In mice with an intact intestinal microbiota, dietary supplementation with TMAO or either carnitine or choline reduced in vivo reverse cholesterol transport. Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk.

Supra-additive expression of interleukin-6, interleukin-8 and basic fibroblast growth factor in vascular smooth muscle cells following coinfection with Chlamydia pneumoniae and cytomegalovirus as a novel link between infection and atherosclerosis.

Chlamydia pneumoniae and human cytomegalovirus (HCMV) may be involved in the pathogenesis of atherosclerosis. Prospective studies indicate an increased risk for cardiovascular events in patients with evidence of multiple infections.

OBJECTIVE:

To determine whether there is a synergistic effect of coinfection with C pneumoniae and HCMV on expression of selected growth factors and cytokines.

METHODS:

The production of interleukin (IL)-6, IL-8, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and 'regulated on activation normal T-cell expressed and secreted' (RANTES) was measured in coinfected aortic smooth muscle cells (AoSMC).

RESULTS:

Using reverse transcription polymerase chain reaction and immunoassays, it was demonstrated that the expression of IL-6, IL-8, RANTES and bFGF was stimulated in a dose- and time-dependent fashion in C pneumoniae and also in HCMV-infected cultures. In contrast, the expression of PDGF-AA was only stimulated following HCMV infection. Coinfection with C pneumoniae and HCMV resulted in a supra-additive stimulation of IL-6 (30% increased expression, P≤0.05) at 48 h, IL-8 (137% increased expression, P≤0.001) at 24 h and bFGF (209% increased expression, P≤0.01) at 48 h following infection.

CONCLUSIONS:

The findings of the present study show that C pneumoniae and HCMV are able to act in synergy in coinfected AoSMC. The supra-additive induction of AoSMC growth factors and cytokines indicates a novel molecular link between infection and vascular disease development.

Air Pollution Tied To Hardening Of Arteries

MNT:  "Over time, increased exposure to air pollution is linked to faster "hardening" of the arteries, or atherosclerosis, a leading cause of heart attacks and strokes. Conversely, exposure to reduced levels of air pollution is linked to slowed progression of atherosclerosis. These are the findings of a new study from the US published this week in PLOS Medicine. "

PLOS ONE: Mitotic Spindle Defects and Chromosome Mis-Segregation Induced by LDL/Cholesterol—Implications for Niemann-Pick C1, Alzheimer’s Disease, and Atherosclerosis

Elevated low-density lipoprotein (LDL)-cholesterol is a risk factor for both Alzheimer’s disease (AD) and Atherosclerosis (CVD), suggesting a common lipid-sensitive step in their pathogenesis. Previous results show that AD and CVD also share a cell cycle defect: chromosome instability and up to 30% aneuploidy–in neurons and other cells in AD and in smooth muscle cells in atherosclerotic plaques in CVD. Indeed, specific degeneration of aneuploid neurons accounts for 90% of neuronal loss in AD brain, indicating that aneuploidy underlies AD neurodegeneration. Cell/mouse models of AD develop similar aneuploidy through amyloid-beta (Aß) inhibition of specific microtubule motors and consequent disruption of mitotic spindles. Here we tested the hypothesis that, like upregulated Aß, elevated LDL/cholesterol and altered intracellular cholesterol homeostasis also causes chromosomal instability. Specifically we found that: 1) high dietary cholesterol induces aneuploidy in mice, satisfying the hypothesis’ first prediction, 2) Niemann-Pick C1 patients accumulate aneuploid fibroblasts, neurons, and glia, demonstrating a similar aneugenic effect of intracellular cholesterol accumulation in humans 3) oxidized LDL, LDL, and cholesterol, but not high-density lipoprotein (HDL), induce chromosome mis-segregation and aneuploidy in cultured cells, including neuronal precursors, indicating that LDL/cholesterol directly affects the cell cycle, 4) LDL-induced aneuploidy requires the LDL receptor, but not Aß, showing that LDL works differently than Aß, with the same end result, 5) cholesterol treatment disrupts the structure of the mitotic spindle, providing a cell biological mechanism for its aneugenic activity, and 6) ethanol or calcium chelation attenuates lipoprotein-induced chromosome mis-segregation, providing molecular insights into cholesterol’s aneugenic mechanism, specifically through its rigidifying effect on the cell membrane, and potentially explaining why ethanol consumption reduces the risk of developing atherosclerosis or AD. These results suggest a novel, cell cycle mechanism by which aberrant cholesterol homeostasis promotes neurodegeneration and atherosclerosis by disrupting chromosome segregation and potentially other aspects of microtubule physiology.

Atherosclerosis: Specific microRNAs promote inflammation

 "Atherosclerosis, an inflammatory reaction, is at the root of the most common forms of cardiovascular disease. Researchers at Ludwig-Maximilians-Universitaet in Munich have now identified a microRNA that plays a prominent role in the process, and offers a promising target for new therapies."

'via Blog this'

Drug shows potential to delay onset or progression of Alzheimer's disease

A research team led by Robert Nagele, PhD, of the New Jersey Institute for Successful Aging (NJISA) at the University of Medicine and Dentistry of New Jersey (UMDNJ)-School of Osteopathic Medicine, has demonstrated that the anti-atherosclerosis drug darapladib can significantly reduce leaks in the blood brain barrier. This finding potentially opens the door to new therapies to prevent the onset or the progression of Alzheimer's disease.

Symptomatic atherosclerosis is associated with an altered gut metagenome.

Recent findings have implicated the gut microbiota as a contributor of metabolic diseases through the modulation of host metabolism and inflammation. Atherosclerosis is associated with lipid accumulation and inflammation in the arterial wall, and bacteria have been suggested as a causative agent of this disease. Here we use shotgun sequencing of the gut metagenome to demonstrate that the genus Collinsella was enriched in patients with symptomatic atherosclerosis, defined as stenotic atherosclerotic plaques in the carotid artery leading to cerebrovascular events, whereas Roseburia and Eubacterium were enriched in healthy controls. Further characterization of the functional capacity of the metagenomes revealed that patient gut metagenomes were enriched in genes encoding peptidoglycan synthesis and depleted in phytoene dehydrogenase; patients also had reduced serum levels of β-carotene. Our findings suggest that the gut metagenome is associated with the inflammatory status of the host and patients with symptomatic atherosclerosis harbor characteristic changes in the gut metagenome.

Inflammation may be a cause of plaque buildup in heart vessels

Inflammation may be a cause of plaque buildup in heart vessels: "ScienceDaily (Dec. 2, 2012) — Fifteen new genetic regions associated with coronary artery disease have been identified by a large, international consortium of scientists -- including researchers at the Stanford University School of Medicine -- taking a significant step forward in understanding the root causes of this deadly disease. The new research brings the total number of validated genetic links with heart disease discovered through genome-wide association studies to 46."

'via Blog this'

Lipid and protein oxidation in female patients with chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is a widely recognized problem, characterized by prolonged, debilitating fatigue and a characteristic group of accompanying symptoms, that occurs four times more frequently in women than in men. The aim of the study was to determine the existence of oxidative stress and its possible consequences in female patients with CFS.

MATERIAL AND METHODS:

Twenty-four women aged 15-45 who fulfilled the diagnostic criteria for CFS with no comorbidities were recruited and were age matched to a control group of 19 healthy women. After conducting the routine laboratory tests, levels of the lipid oxidation product malondialdehyde (MDA) and protein oxidation protein carbonyl (CO) were determined.

RESULTS:

The CFS group had higher levels of triglycerides (p = 0.03), MDA (p = 0.03) and CO (p = 0.002) and lower levels of HDL cholesterol (p = 0.001) than the control group. There were no significant differences in the levels of total protein, total cholesterol or LDL cholesterol.

CONCLUSIONS:

The CFS group had an unfavorable lipid profile and signs of oxidative stress induced damage to lipids and proteins. These results might be indicative of early proatherogenic processes in this group of patients who are otherwise at low risk for atherosclerosis. Antioxidant treatment and life style changes are indicated for women with CFS, as well as closer observation in order to assess the degree of atherosclerosis.

Controlling Vascular Disease May Be Key to Reducing Prevalence of Alzheimer’s Disease | IOS Press

Over the last 15 years, researchers have found a significant association between vascular diseases such as hypertension, atherosclerosis, diabetes type 2, hyperlipidemia, and heart disease and an increased risk of Alzheimer’s disease. In a special issue of the Journal of Alzheimer’s Disease, leading experts provide a comprehensive overview of the pathological, biochemical, and physiological processes that contribute to Alzheimer’s disease risk and ways that may delay or reverse these age-related abnormalities.