Tag Archives: blood platelet pro

Is Your Type of Heart Disease Curable of Just Treatable?

Can Your Type of Heart Disease be Cured or Just Treated?

Because of the growing list on the Real Poisoning of America – Glycation, it’s become evident that I need to display a different post for the different types of damage that glycation induces. From atherosclerosis and other heart related diseases, I’ll reserve this notice for that purpose only. All cancer reports will be located on the cancer page.  Dementia will be on a separate post as well with all other diseases and disorders inflammation is responsible for.

The whole premise behind these posts is to prove that the only way you can prevent these horrendous diseases, is to stop the glycation that is responsible for them and the only way you can stop the glycation is to stop feeding it. It’s really a simple solution, just not an easy one because of the addiction factor. However, YOU and only YOU have control over this and it all depends on what YOU put in you mouth when you eat.

I’ll admit that that can be hard when you have a whole industry trying to get you to eat more of what it is that glycates. This is because they are connected to another industry that feeds off of the unsuspected that buy into this ruse, all those whom the glycation affects, the public.                                               Get the whole story!

Listed below from PubMed or PMC or the FDA are reports of studies done on the effects of glycation and its influence in any CVD or disease influenced by inflammation, which is a direct cause of glycation.

Advanced glycation endproducts induce apoptosis of endothelial progenitor cells by activating receptor RAGE and NADPH oxidase/JNK signaling axis.

Elevated levels of advanced glycation endproducts (AGEs) is an important risk factor for atherosclerosis. Dysfunction of endothelial progenitor cells (EPCs), which is essential for re-endothelialization and neovascularization, is a hallmark of atherosclerosis. However, it remains unclear whether and how AGEs acts on EPCs to promote pathogenesis of atherosclerosis. In this study, EPCs were exposed to different concentrations of AGEs. The expression of NADPH and Rac1 was measured to investigate the involvement of NADPH oxidase pathway. ROS was examined to indicate the level of oxidative stress in EPCs. Total JNK and p-JNK were determined by Western blotting. Cell apoptosis was evaluated by both TUNEL staining and flow cytometry. Cell proliferation was measured by (3)H thymidine uptake. The results showed that treatment of EPCs with AGEs increased the levels of ROS in EPCs. Mechanistically, AGEs increased the activity of NADPH oxidase and the expression of Rac1, a major component of NADPH. Importantly, treatment of EPCs with AGEs activated the JNK signaling pathway, which was closely associated with cell apoptosis and inhibition of proliferation. Our results suggest that the RAGE activation by AGEs in EPCs upregulates intracellular ROS levels, which contributes to increased activity of NADPH oxidase and expression of Rac1, thus promoting cellular apoptosis and inhibiting proliferation. Mechanistically, AGEs binding to the receptor RAGE in EPCs is associated with hyperactivity of JNK signaling pathway, which is downstream of ROS. Our findings suggest that dysregulation of the AGEs/RAGE axis in EPCs may promote atherosclerosis and identify the NADPH/ROS/JNK signaling axis as a potential target for therapeutic intervention.

With the list growing past 17,729 studies on the effects of glycation, I think this message about the process of glycation should be wider known. This is the basis of all modern disease. Why has it been kept hidden? Is it due to industrial concerns? What would happen if you wiped 98% of all illness?

This report dictates how the modification of proteins (glycation) is involved in atherosclerosis. Is this the smoking gun that carbs are dangerous foods to eat? Even though this report is from Dec 2016, it only says, again, what hundreds if not thousands of other reports dictate. They all dictate glycation is dangerous. What causes glycation should be avoided at all costs, to ensure optimal health.

Post-translational modification of proteins imparts diversity to protein functions. The process of glycation represents a complex set of pathways that mediates advanced glycation endproduct (AGE) formation, detoxification, intracellular disposition, extracellular release, and induction of signal transduction. These processes modulate the response to hyperglycemia, obesity, aging, inflammation, and renal failure, in which AGE formation and accumulation is facilitated. It has been shown that endogenous anti-AGE protective mechanisms are thwarted in chronic disease, thereby amplifying accumulation and detrimental cellular actions of these species. Atop these considerations, receptor for advanced glycation endproducts (RAGE)-mediated pathways down regulate expression and activity of the key anti-AGE detoxification enzyme, glyoxalase-1 (GLO1), thereby setting in motion an interminable feed-forward loop in which AGE-mediated cellular perturbation is not readily extinguished. In this review, we consider recent work in the field highlighting roles for glycation in obesity and atherosclerosis and discuss emerging strategies to block the adverse consequences of AGEs. This article is part of a Special Issue entitled: The role of post-translational protein modifications on heart and vascular metabolism edited by Jason R.B. Dyck & Jan F.C. Glatz.

This is the smoking gun that proves what glucose consumption does to the body in the form of atherosclerosis. How long before the FDA or the USDA will admit that this is what happens after ingesting grains? Will the Heart Association say anything about this? What about the American Diabetic Association? I wonder if this news will reach any regulatory agency. My guess is if Monsanto has anything to say about it, they’ll say “where’s the money in it.”

This report from Aug 1 1989, reveals how aware we were then, that glycation is a damaging process that is caused by excess glucose in your system. One would think that 27 and a half years would be long enough to reveal this information. Apparently, it isn’t.

We studied 11 diabetic patients, all of whom had severe atherothrombotic disease, and 11 normal controls. Overall glycation was assessed by the extent of incorporation of [3H]-NaBH4 into fructosyl lysine separated from whole platelet proteins following amino acid analysis. Fructosyl lysine represented 5.7% +/- 1.0 S.D. of the total radioactivity in the normal whole platelet samples. Increased glycation was observed in platelets from 5 of the 11 diabetics. Platelet glycation did not correlate with glycation of hemoglobin or albumin. The pattern of glycation of various platelet proteins in whole platelets, as determined by the incorporation of [3H]-NaBH4 into electrophoretically separated proteins did not display selectivity, although myosin and glycoproteins IIb and IIIa showed relatively increased levels of [3H]-NaBH4 incorporation. Artificially glycated platelet membranes exhibited glycation mainly in proteins corresponding to the electrophoretic mobility of myosin, glycoproteins IIb and IIIa.

The previous report was published in 1989 yet have you heard anything about it? Didn’t they have idea, at that time, what carbs were doing to the body, when ingested? I guess they needed more studies. Over 17,000 of them have been filed as of yet. Why has it taken until 2010 to learn any of this? Even today, they still are reluctant to admit such, that carbs are dangerous foods to be eating.

  • Advancedglycation end products: An emerging biomarker for adverse outcome in patients with peripheral artery disease.

Patients with peripheral artery disease (PAD) suffer from widespread atherosclerosis. Partly due to the growing awareness of cardiovascular disease, the incidence of PAD has increased considerably during the past decade. It is anticipated that algorithms to identify high risk patients for cardiovascular events require being updated, making use of novel biomarkers. Advanced glycation end products (AGEs) are moieties formed non-enzymatically on long-lived proteins under influence of glycemic and oxidative stress reactions. We elaborate about the formation and effects of AGEs, and the methods to measure AGEs. Several studies have been performed with AGEs in PAD. In this review, we evaluate the emerging evidence of AGEs as a clinical biomarker for patients with PAD.

Peripheral Artery disease is often the start of Atherosclerosis and all CVDs. They are a direct cause of glycation. Glycation is controllable by controlling the amount of carbs you put in your mouth every time you eat.

This following study shows how your body reacts to the glucose infusion by sending out macrophages to counteract the damage presented by the glucose. The modified LDL particles are the glycated endproducts of what happens to your cholesterol with glucose in your system.

How do macrophages sense modified low-density lipoproteins?

Abstract

In atherosclerosis, serum lipoproteins undergo various chemical modifications that impair their normal function. Modification of low density lipoprotein (LDL) such as oxidation, glycation, carbamylation, glucooxidation, etc. makes LDL particles more proatherogenic. Macrophages are responsible for clearance of modified LDL to prevent cytotoxicity, tissue injury, inflammation, and metabolic disturbances. They develop an advanced sensing arsenal composed of various pattern recognition receptors (PRRs) capable of recognizing and binding foreign or altered-self targets for further inactivation and degradation. Modified LDL can be sensed and taken up by macrophages with a battery of scavenger receptors (SRs), of which SR-A1, CD36, and LOX1 play a major role. However, in atherosclerosis, lipid balance is deregulated that induces inability of macrophages to completely recycle modified LDL and leads to lipid deposition and transformation of macrophages to foam cells. SRs also mediate various pathogenic effects of modified LDL on macrophages through activation of the intracellular signaling network. Other PRRs such Toll-like receptors can also interact with modified LDL and mediate their effects independently or in cooperation with SRs.

What you should think about, is what would happen if the glucose weren’t there. The cholesterol can do what it’s supposed to do, feed your body.

From Dec 2016, Coronary Heart Disease and Ischemic stroke are shown to be influenced by another RAGE Gly82ser. How many more of these do they have to find before they realize that you can prevent this by keeping carbs out of the diet?

Association of RAGE gene Gly82Ser polymorphism with coronary artery disease and ischemic stroke: A systematic review and meta-analysis.

Abstract

BACKGROUND:

The receptor for advanced glycosylation end products (RAGE) has been widely linked to diabetic atherosclerosis, but its effects on coronary artery disease (CAD) and ischemic stroke (IS) remain controversial. The Gly82Ser polymorphism is located in the ligand-binding V domain of RAGE, suggesting a possible influence of this variant on RAGE function. The aim of the present study is to clarify the association between the RAGE Gly82Ser polymorphism and susceptibility to CAD and IS.

CONCLUSIONS:

The current meta-analysis suggests that the RAGE Gly82Ser polymorphism is associated with an increased risk of CAD and IS, especially in the Chinese population. However, better-designed studies with larger sample sizes are needed to validate the results.

The following report submitted Sep 31, 2011 shows the influence of RAGE in VRD ;

RAGE-dependent activation of the onco-protein Pim1 plays a critical role in systemic vascular remodeling processes.

Abstract

OBJECTIVE:

Vascular remodeling diseases (VRD) are mainly characterized by inflammation and a vascular smooth muscle cells (VSMCs) proproliferative and anti-apoptotic phenotype. Recently, the activation of the advanced glycation endproducts receptor (RAGE) has been shown to promote VSMC proliferation and resistance to apoptosis in VRD in a signal transducer and activator of transcription (STAT)3-dependant manner. Interestingly, we previously described in both cancer and VRD that the sustainability of this proproliferative and antiapoptotic phenotype requires activation of the transcription factor NFAT (nuclear factor of activated T-cells). In cancer, NFAT activation is dependent of the oncoprotein provirus integration site for Moloney murine leukemia virus (Pim1), which is regulated by STAT3 and activated in VRD. Therefore, we hypothesized that RAGE/STAT3 activation in VSMC activates Pim1, promoting NFAT and thus VSMC proliferation and resistance to apoptosis. Methods/Results- In vitro, freshly isolated human carotid VSMCs exposed to RAGE activator Nε-(carboxymethyl)lysine (CML) for 48 hours had (1) activated STAT3 (increased P-STAT3/STAT3 ratio and P-STAT3 nuclear translocation); (2) increased STAT3-dependent Pim1 expression resulting in NFATc1 activation; and (3) increased Pim1/NFAT-dependent VSMC proliferation (PCNA, Ki67) and resistance to mitochondrial-dependent apoptosis (TMRM, Annexin V, TUNEL). Similarly to RAGE inhibition (small interfering RNA [siRNA]), Pim1, STAT3 and NFATc1 inhibition (siRNA) reversed these abnormalities in human carotid VSMC. Moreover, carotid artery VSMCs isolated from Pim1 knockout mice were resistant to CML-induced VSMC proliferation and resistance to apoptosis. In vivo, RAGE inhibition decreases STAT3/Pim1/NFAT activation, reversing vascular remodeling in the rat carotid artery-injured model.

CONCLUSIONS:

RAGE activation accounts for many features of VRD including VSMC proliferation and resistance to apoptosis by the activation of STAT3/Pim1/NFAT axis. Molecules aimed to inhibit RAGE could be of a great therapeutic interest for the treatment of VRD.

Advanced glycation end products increase lipids accumulation in macrophages through upregulation of receptor of advanced glycation end products: increasing uptake, esterification and decreasing efflux of cholesterol.

Advanced glycation end products increase lipids accumulation in macrophages through upregulation of receptor of advanced glycation end products: increasing uptake, esterification and decreasing efflux of cholesterol.

BACKGROUND:

Previous reports have suggested that advanced glycation end products (AGEs) participate in the pathogenesis of diabetic macroangiopathy. Our previous study have found that AGEs can increase the lipid droplets accumulation in aortas of diabetic rats, but the current understanding of the mechanisms remains incomplete by which AGEs affect lipids accumulation in macrophages and accelerate atherosclerosis. In this study, we investigated the role of AGEs on lipids accumulation in macrophages and the possible molecular mechanisms including cholesterol influx, esterification and efflux of macrophages.

METHODS:

THP-1 cells were incubated with PMA to differentiate to be macrophages which were treated with AGEs in the concentration of 300 μg/ml and 600 μg/ml with or without anti-RAGE (receptor for AGEs) antibody and then stimulated by oxidized-LDL (oxLDL) or Dil-oxLDL. Lipids accumulation was examined by oil red staining. The cholesterol uptake, esterification and efflux were detected respectively by fluorescence microscope, enzymatic assay kit and fluorescence microplate. Quantitative RT-PCR and Western blot were used to measure expression of the moleculars involved in cholesterol uptake, synthesis/esterification and efflux.

RESULTS:

AGEs increased lipids accumulation in macrophages in a concentration-dependent manner. 600 μg/ml AGEs obviously unregulated oxLDL uptake, increased levels of cholesterol ester in macrophages, and decreased the HDL-mediated cholesterol efflux by regulating the main molecular expression including CD36, Scavenger receptors (SR) A2, HMG-CoA reductase (HMGCR), ACAT1 and ATP-binding cassette transporter G1 (ABCG1). The changes above were inversed when the cells were pretreated with anti-RAGE antibody.

CONCLUSIONS:

The current study suggest that AGEs can increase lipids accumulation in macrophages by regulating cholesterol uptake, esterification and efflux mainly through binding with RAGE, which provide a deep understanding of mechanisms how AGEs accelerating diabetic atherogenesis.

This is the proof that AGEs inhibit proper cell nutrition by preventing the flow of cholesterol into the cell. This allows accumulation of LDL particles in your blood. Usually with a carbohydrate diet, those LDL particles are going to be ApoB particles and those are the most proliferate in all disease. Again, this is something you have full control over, as you don’t have to eat this food. There are plenty of healthier alternatives.

The next study details how glycol-AGEs work their way into the cellular wall of your arteries creating Atherosclerosis. What you should think about is, could this happen without glucose in your system? Can you live without glucose? If you answered YES to both of those questions, you’re on your way to a healthier body.

Glycolaldehyde-derived advanced glycation end products (glycol-AGEs)-induced vascular smooth muscle cell dysfunction is regulated by the AGES-receptor (RAGE) axis in endothelium.

Advanced glycation end-products (AGEs) are involved in the development of vascular smooth muscle cell (VSMC) dysfunction and the progression of atherosclerosis. However, AGEs may indirectly affect VSMCs via AGEs-induced signal transduction between monocytes and human umbilical endothelial cells (HUVECs), rather than having a direct influence. This study was designed to elucidate the signaling pathway underlying AGEs-RAGE axis influence on VSMC dysfunction using a co-culture system with monocytes, HUVECs and VSMCs. AGEs stimulated production of reactive oxygen species and pro-inflammatory mediators such as tumor necrosis factor-α and interleukin-1β via extracellular-signal-regulated kinases phosphorylation and nuclear factor-κB activation in HUVECs. It was observed that AGEs-induced pro-inflammatory cytokines increase VSMC proliferation, inflammation and vascular remodeling in the co-culture system. This result implies that RAGE plays a role in AGEs-induced VSMC dysfunction. We suggest that the regulation of signal transduction via the AGEs-RAGE axis in the endothelium can be a therapeutic target for preventing atherosclerosis.

Do you have any idea of how to regulate the transduction of AGEs? It’s simple, go keto. Will an industry that depends on your illness, tell you that? I seriously doubt it. Since it’s this industry that regulates the regulatory agencies, I doubt that you’ll ever hear it from them. That’s why it’s so important to follow your own advice to stay healthy, stay away from unhealthy substances. Now you know how unhealthy glucose is, simply due to its glycative effects.

Are these enough reports to prove how directly influence diabetes? After reading this can you see the logic in controlling your diabetes by controlling your carb intake? Where are the warnings from the FDA and the USDA? Don’t they care about what they’re recommending? Don’t they understand because of their recommendations, they sending millions of Moms and Dads, sisters and brothers, husbands and wives to their slow, expensive, painful deaths?

These are free reports that are available to everyone. All you have to do is search for them at the National Library of Medicine in the National Institute of Health. There are literally 100s of thousands of reports on the effects of glycation that remain hidden in the PubMed and PMC databases except to the few who look through them.  The only ones looking through this database are the drug companies looking for more ways to make money. Nobody is looking to warn anyone of the dangers of this food.

My question is why? The answer I get is, “there’s no money in it”. That’s is why I said in my first book, it would be a shame if profits and money weren’t the primary motivating factors in our society, but they are, and we have to live with it. That’s why I choose not to buy into it. It’s the same choice you have.