Heart Disease Part Two by Jeffrey Dach MD
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 (Above Image Courtesy of Eve Garrison Art Foundation) Heart Disease Part Two - Atherosclerosis: How Does it Happen? A Brief Review of Part I The previous report discussed the Coronary Calcium Score, which is useful because it provides an estimate of total plaque burden. We also made the shocking statement that the conventional lipid panel is now obsolete. It has been replaced by the more sophisticated lipoprotein panel called the NMR or the VAP, which gives truly useful information of risk markers such as the LDL particle size and Lipoprotein (a). We also discussed treatment strategies with dietary modification and various nutritional supplements such as niacin, fish oil, L-arginine etc which can slow or reverse plaque formation. My two previous reports have discussed the role of statin drugs and their adverse side effects.(7)(8)  In Part I, we explained how plaque formation is the cause of heart disease, and also discussed how enlarging plaques eventually cause heart attack by either occlusion, or plaque rupture with thrombosis. Although there is usually some warning such as chest pain or shortness of breath, sudden plaque rupture with thrombosis may cause a heart attack without warning. (Image at Left Courtesy of Wikipedia the Cholesterol Molecule) Part Two - A Closer Look at Plaque Formation In Part II of this report we take a closer look at the individual steps leading to plaque formation in the artery wall. Based on this knowledge, we will then suggest additional strategies for preventing and reversing plaque formation in the arteries. An Excellent Review Article on Atherosclerosis An excellent review article on the detailed mechanism of atherosclerotic plaque formation can be found here by Navab from UCLA. (2) Understanding the Events Leading to Atherosclerosis -The Fatty Streak  The Linus Pauling Theory - Vitamin C Deficiency -Cholesterol Patches Linus Pauling and others, suspected that the LDL deposition in the wall serves as patching material to repair small cracks in the arterial wall at sites of mechanical stress from pulsations and flow turbulence. Pauling theorized that, because of a subclinical vitamin C deficiency, the normal repair mechanisms are ineffective, so that an alternate repair mechanism with LDL cholesterol evolved. The LDL cholesterol serves as a sort of rubber cement to patch up the cracks in arteries, just like patching the inner tube of our tires. Since the appearance of the fatty streak appears so early (in the fetus), it is highly likely that there is a constant ebb and flow of lipoprotein material in and out of the arterial wall. We now know there is a transport mechanism for cholesterol to travel in the blood stream to the arterial wall in the form of LDL particles. And, there is a reverse cholesterol transport mechanism which transports cholesterol back from the artery wall to the liver in the form of HDL particles using the LCAT enzyme (Lecithin-Cholesterol Acetyl Transferase). Cholesterol Transport -Good (HDL) and Bad (LDL) Cholesterol  At left is a blow up of a microscopic LDL particle with the APO-B protein colored in yellow, attached at the top. Cholesterol (orange) is contained in the center, and is encapsulated by an outer bi-layer of phospholipid (purple).(Image at Left Copyright 2008 Jeffrey Dach MD, LDL particle) The HDL particle has a similar configuration except that the Yellow protein at the top is replaced with the AP0-A1 protein. The LDL particles are transported from the liver out to the body tissues in the blood stream and delivers cholesterol to the Fatty Streak in the artery wall. The HDL particles carry cholesterol from the Fatty Streak in the artery wall back to the liver where it is metabolized and excreted as bile. Calling LDL "bad", and HDL "good" is like calling the ambulance that comes from the hospital to your home the "bad" one, and the ambulance that takes you back to the hospital , the "good" one. Perhaps this is a useful analogy for children, but is overly simplistic for adults.(4) Oxidized Cholesterol The reality is that LDL cholesterol itself is not the culprit, rather it is oxidized LDL that is the "bad" guy. Lowering plain LDL cholesterol will also lower the oxidized fraction of LDL cholesterol, but this is a rather crude way to do it. Cholesterol is a building block for membranes and sex steroids, is important for over-all health, and lower cholesterol is associated with increased mortality from cancer, liver disease and mental disease. (5)(6) Perhaps this is the reason why lowering cholesterol with statin drugs can reduce "cardiac events", but sadly, statin drugs have little or no benefit in terms of all-cause mortality. (7)(8) It would be much more beneficial to selectively reduce only the OXIDIZED LDL cholesterol. Researchers have tests to measure oxidized LDL cholesterol, but this is not yet available to clinicians, and should be. The Role of Anti-Oxidants Selectively reducing Oxidized LDL is exactly what is done with anti-oxidants like vitamin C, E, Carotenoids, and Red wine polyphenols. These dietary supplements as well as a healthy diet and lifestyle are clearly beneficial.(9) However, many people are confused by the opposition views in the medical literature and the media. These views oppose the use of dietary supplements to prevent heart disease. Some have even proposed the bizarre notion that vitamins increase mortality. Of course, these views represent the interests of the pharmaceutical industry which stands to lose billions from reduction in heart disease and reduced demand for drugs.(10)(11)(12)(13)(14) It is clear that dietary antioxidants like carotinoids in fresh vegetables as well as red wine polyphenols inhibit LDL oxidation and reduce heart disease.(15) We will later look at novel anti-oxidants such as liposomal glutathione (16) and Boswellia. Infiltration by Monocytes- Macrophages and Inflammation  The next step in plaque formation is the infiltration of cells into the wall of the artery. Current thinking is that oxidized LDL attracts the influx of monocytes. These are cells in the blood stream which have the ability to transform themselves into large scavenger cells called macrophages which serve as the garbage trucks for pick up and disposal. They engulf, digest and dispose of the old or toxic stuff the body needs to get rid of. These macrophages engulf the LDL cholesterol, and try to dispose of it. During the disposal process more of the LDL is oxidized . Something goes wrong at this step , and the macrophages continue to accumulate more and more oxidized LDL until the poor cell looks like an over inflated balloon ready to burst. This becomes the Foam Cell. The Foam Cell- The Culprit is Oxidized LDL This new over-stuffed macrophage is now called a “Foam Cell” because it looks foamy under the microscope. It is clear that the culprit is the oxidized or rancid form of LDL cholesterol. If the LDL is not oxidized, there seems to be no problem and the LDL can be transported out of the artery back to the liver in the form of HDL using the LCAT enzyme for reverse cholesterol transport. The Foam Cells accumulate, and send out more chemical messages which invokes an inflammatory cascade that attracts more macrophages and other cells in an inflammatory reaction. This inflammation in the wall of the artery causes the thickening in the wall called plaque formation. The Fibrous Cap The last step in plaque formation is the fibrous cap which creates a seal between the puddle of oxidized LDL and its inflammatory cells and the flowing blood at the interior of the artery. Rupture of the fibrous cap is the final event which exposes the thrombogenic plaque to the blood stream causing clot formation and a heart attack. How to Prevent Oxidation of LDL cholesterol Now that we know the events leading to plaque formation and rupture, we can create a logical plan to prevent and reverse this process. Much of this information was covered in Part One of this article. Even after LDL becomes oxidized, it can be converted back to its original form with the use of anti-oxidants in a process called reduction. There are a number of anti-oxidants which have been shown effective. The most important and most powerful intracellular antioxidant is glutathione, a simple structure composed of three amino acids and sulfur. What is Glutathione? Glutathione is the most powerful naturally occurring antioxidant in all human cells. It is a small simple compound composed of three amino acids, glutamic acid, cysteine and glycine. Cysteine contains sulfer accounting for its sulfer taste and smell. Glutathione is found in all cells in the body, and the highest concentration in the liver, important for detoxification and elimination of toxins and products of oxidation called free radicals. For the past 10 years, Glutathione has been available only as an intravenous agent. David Perlmutter MD in Naples Florida has been pioneering the use of IV glutathione in Parkinson’s Disease patients for the past 10 years with dramatic results. These Parkinson’s patients have immediate improvement in their symptoms after Glutathione IV infusion. In addition, inhaled glutathione in the form of a nebulizer has been beneficial for chronic obstructive lung disease patients. Liposomal Glutathione Reduces Plaque by 30% A recent 2007 publication from the Technion in Haifa showed that Liposomal Glutathione reduced plaque formation by 30% in genetically modified Apo-E mice. (16) These are mice that have accelerated atherosclerosis, the mouse equivalent of familial hypercholesterolemia in humans. They also found glutathione peroxidase in the LDL particle itself, an enzyme that allows the glutathione to refresh the oxidized LDL back to its original reduced form. How convenient this enzyme is already in place on the LDL particle. It must be part of some plan. At the recent ACAM meeting in Orlando (April 2008), Tim Guilford MD presented the data on Liposomal Glutathione reversing plaque in Apo-E mice. Technion researchers in this 2007 study used Dr. Guilford's liposomal glutathione product called Readisorb, which is available at his web site. What is Boswellia ? Oxidation of the LDL cholesterol involves the Lipoxygenase pathway which can be inhibited by Boswellia. Boswellia works by suppressing inflammation by inhibiting an enzyme called 5-lipoxygenase (5 L-OX) and its by products called leukotrienes. This pathway is important in chronic inflammatory diseases such as arthritis, colitis, asthma, allergies, osteoporosis, eczema and psoriasis. Boswellia is also useful in preventing the inflammation inside the arterial tree associated with atherosclerotic plaque formation. In mice where the 5-lipoxygenase is absent there is a 26 fold reduction in atherosclerotic plaque compared to controls. (17) Currently mainstream medicine has no drug to control the 5-L-OX enzyme, because up to now the pharmaceutical industry has not been able to make such a drug without major adverse side effects. However, Boswellia is a safe, natural gum resin of the frankincense tree, which powerfully suppresses the 5-lipoxygenase enzyme like no other substance known. Ancient traditional uses and more recent studies have shown significant improvements in asthma, arthritis, colitis, allergies, and heart disease. The most active of Frankincense component is called AKBA (acetyl-11-keto-beta-boswellic acid ). Unfortunately, currently available Boswellia extracts contain only a small amount of AKBA in the range of 1-3%. This small amount makes it virtually impossible to attain plasma levels needed for any real clinical benefit. Fortunately, a new Boswellia extract contains the more active 90% AKBA and is available from True Botanica (Ross Rentea MD). Thematic review series: The Pathogenesis of Atherosclerosis The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL Mohamad Navab1,*, G. M. Ananthramaiah, Srinivasa T. Reddy*,, Brian J. Van Lenten*, Benjamin J. Ansell*, Gregg C. Fonarow*, Kambiz Vahabzadeh*, Susan Hama*, Greg Hough*, Naeimeh Kamranpour*, Judith A. Berliner*,**, Aldons J. Lusis*,, and Alan M. Fogelman*
Role of Oxidative Modifications in Atherosclerosis Roland Stocker and John F. Keaney, Jr. Emerging evidence has heightened the interest in the contribution of lipoxygenase to atherosclerosis. Analysis of atherosclerosis-prone and atherosclerosis-resistant mice identified a region on chormosome 6 that conferred resistance to atherosclerosis despite elevated levels of lipids (614). Further analysis of this locus determined that 5-lipoxygenase was one putative gene on chromasome 6 that conferred susceptibility to atherosclerosis (613). LDL OXIDATION: CAUSE OR CONSEQUENCE OF ATHEROSCLEROSIS. It is important to recognize that a large body of the support referred to in this review to substantiate the oxidative modification hypothesis of atherosclerosis provides indirect rather than direct evidence for a causative link between the two processes. This is perhaps not surprising given the difficulties in experimental attempts to distinguish LDL oxidation as a cause rather than consequence of atherosclerosis. For example, associations such as the relative extent of LDL oxidation in the vessel wall and disease burden at best only strengthen the oxidative modification hypothesis; they do not prove the hypothesis. (4) http://www.jpands.org/vol10no3/colpo.pdf Annals of Clinical & Laboratory Science 37:343-348 (2007) In men, across the entire age range, although of borderline significance under the age of 50, and in women from the age of 50 onward only, low cholesterol was significantly associated with all-cause mortality, showing significant associations with death through cancer, liver diseases, and mental diseases. (Circulation. 2003;107:947.)Clinical Investigation and Reports Six-Year Effect of Combined Vitamin C and E Supplementation on Atherosclerotic Progression - The Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study Conclusions— These data replicate our 3-year findings confirming that the supplementation with combination of vitamin E and slow-release vitamin C slows down atherosclerotic progression in hypercholesterolemic persons These biased articles are based on the latest Cochrane review which more or less copies the JAMA paper from February 2007. Unfortunately, bad science and misleading media stories are confusing consumers. As dietary supplements become more popular and threaten the bottom line of traditional medicine and Big Pharma, we see more and more studies and articles that try to convince the public that dietary supplements are useless, unregulated, or even deadly. A recent review of clinical trials by Bjelakovic et al. (JAMA Feb 2007) claimed to show that certain antioxidant What is the Efficacy of Single Vitamin and Mineral Supplement Use in Chronic Disease Prevention? Heart disease and single-vitamin supplementation1,2,3,4 Maret G Traber American Journal of Clinical Nutrition, Vol. 85, No. 1, 293S-299S, January 2007 (15) http://www.ncbi.nlm.nih.gov/pubmed/16596803 Handb Exp Pharmacol. 2005;(170):263-300 Dietary antioxidants and paraoxonases against LDL oxidation and atherosclerosis development. Aviram M, Kaplan M, Rosenblat M, Fuhrman B.The Lipid Research Laboratory, Technion Faculty of Medicin and Rambam Medical Center, Haifa, Israel. Oxidative modification of low-density lipoprotein (LDL) in the arterial wall plays a key role in the pathogenesis of atherosclerosis. Under oxidative stress LDL is exposed to oxidative modifications by arterial wall cells including macrophages. Oxidative stress also induces cellular-lipid peroxidation, resulting in the formation of 'oxidized macrophages', which demonstrate increased capacity to oxidize LDL and increased uptake of oxidized LDL. (16) http://www.ncbi.nlm.nih.gov/pubmed/17588583 Anti-oxidant and anti-atherogenic properties of liposomal glutathione: studies in vitro, and in the atherosclerotic apolipoprotein E-deficient mice.Rosenblat M, Volkova N, Coleman R, Aviram M. Liposomal glutathione, but not the control liposomes (with no glutathione), dose-dependently inhibited copper ion-induced low density lipoprotein (LDL) and HDL oxidation. As peroxidase activity was found to be present in both LDL and HDL, it has contributed to the anti-oxidative effects of liposomal glutathione. In-vitro, no significant effect of liposomal glutathione on J774 A.1 macrophage cell-line oxidative stress and on cellular cholesterol metabolism was observed. In contrast, in the atherosclerotic apolipoprotein E-deficient (E(0)) mice, consumption of liposomal glutathione (12.5 or 50mg/kg/day, for 2 months), but not control liposomes, resulted in a significant reduction in the serum susceptibility to AAPH-induced oxidation by 33%. Liposomal glutathione (50mg/kg/day) consumption also resulted in an increment (by 12%) in the mice peritoneal macrophages (MPM) glutathione content, paralleled by a significant reduction in total cellular lipid peroxides content (by 40%), compared to placebo-treated mice MPM. MPM paraoxonase 2 activity was significantly increased by 27% and by 121%, after liposomal glutathione consumption (12.5 or 50mg/kg/day, respectively). (17) http://circres.ahajournals.org/cgi/content/full/91/2/120 Molecular Medicine Identification of 5-Lipoxygenase as a Major Gene Contributing to Atherosclerosis Susceptibility in Mice We previously reported the identification of a locus on mouse chromosome 6 that confers almost total resistance to atherogenesis, even on a hypercholesterolemic (LDL receptor–null) background. (18) http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9389731 C Napoli, F P D'Armiento, F P Mancini, A Postiglione, J L Witztum, G Palumbo, and W Palinski, Department of Clinical and Experimental Medicine, Federico II University of Naples, 80131 Naples, Italy. We found that in LDLR-deficient mice, feeding of an oxidized-cholesterol diet resulted in a 32% increase in fatty streak lesions (15.93±1.59% versus 21.00±1.38%, P<0.03). Similarly, in apo E–deficient mice, feeding of an oxidized-cholesterol diet increased fatty streak lesions by 38% (15.01±0.92% versus 20.70±0.86%, P<0.001). http://atvb.ahajournals.org/cgi/content/abstract/18/6/977 Oxidized Cholesterol in the Diet Accelerates the Development of Aortic Atherosclerosis in Cholesterol-Fed Rabbits Ilona Staprans; Xian-Mang Pan; Joseph H. Rapp; ; Kenneth R. Feingold Abstract—Oxidized lipoproteins may play a role in atherosclerosis. Recently, we have demonstrated that the levels of oxidized fatty acids in the circulation correlate directly with the quantity of oxidized fatty acids in the diet and that dietary oxidized fatty acids accelerate atherosclerosis in rabbits. The present study tests the hypothesis that oxidized cholesterol in the diet accelerates the development of atherosclerosis. Rabbits were fed a diet containing 0.33% nonoxidized cholesterol (control diet) or the same diet containing 0.33% cholesterol of which 5% was oxidized (oxidized diet). Serum cholesterol levels increased to a similar extent in both groups, with the majority of cholesterol in the ß-VLDL fraction. Moreover, in the serum ß-VLDL fraction and liver, there was a significant increase in the oxidized cholesterol levels. Most importantly, feeding a diet enriched in oxidized cholesterol resulted in a 100% increase in fatty streak lesions in the aorta. Western diets contain high concentrations of oxidized cholesterol products, and our results suggest that these foods may be a risk factor for atherosclerosis. http://www.specialtylabs.com/books/display.asp?id=1095 Oxidized Low Density Lipoproteins and their Autoantibodies Modified forms of low density lipoprotein (LDL), the major cholesterol carrying lipoprotein, are associated with accelerated atherosclerosis. Macrophages take up oxidized LDL (ox-LDL) and acetylated LDL (acetyl-LDL) to form foam cells, the earliest step in atherogenesis.1 Probably reflecting their rapid binding to the scavenger receptor on the macrophage immediately after its formation ox-LDL are undetectable in circulating blood, but are detected in atheromatous plaques. Other risk factors for myocardial infarction may have a final common pathway through ox-LDL. For example, homocyst(e)ine and cysteine can induce oxidative modification of LDL.2 Cigarette smoking and hypercholesterolemia synergistically impair endothelial cell function and enhance oxidation of LDL and their combined presence is associated with autoantibodies to ox-LDL.3 Iron catalyzes the formation of reactive oxygen species, which, in turn, leads to the modification of LDL at the molecular level, facilitating its deposition and leading to the formation of artherosclerotic plaque.4 Monoclonal antibodies specific for MDA-modified LDL and ox-LDL are detectable by EIA. Autoantibodies to ox-LDL (ox-LDL-Ab) are considered a good surrogate marker of LDL oxidation. Ox-LDL is more immunogenic than native LDL, and elevated antibodies to ox-LDL are associated with carotid atherosclerosis. Patients with abnormal coronary angiograms have significantly elevated concentrations of ox-LDL-Ab compared to patients with normal coronary angiograms or normal subjects.6 High LDL cholesterol (>3 mmol/L) is associated with poor coronary flow reserve only in patients with elevated ox-LDL-Ab.7 Increased LDL oxidation is associated with coronary artery disease. Oxidized LDL induces atherosclerosis by stimulating monocyte infiltration and smooth muscle cell migration and proliferation. It contributes to atherothrombosis by inducing endothelial cell apoptosis, and thus plaque erosion, by impairing the anticoagulant balance in endothelium, stimulating tissue factor production by smooth muscle cells, and inducing apoptosis in macrophages. HDL cholesterol levels are inversely related to risk of coronary artery disease. HDL prevents atherosclerosis by reverting the stimulatory effect of oxidized LDL on monocyte infiltration. The HDL-associated enzyme paraoxonase inhibits the oxidation of LDL. PAF-acetyl hydrolase, which circulates in association with HDL and is produced in the arterial wall by macrophages, degrades bioactive oxidized phospholipids. Both enzymes actively protect hypercholesterolemic mice against atherosclerosis. Oxidized LDL inhibits these enzymes. Thus, oxidized LDL and HDL are indeed antagonists in the development of cardiovascular disease. We previously reported the identification of a locus on mouse chromosome 6 that confers almost total resistance to atherogenesis, even on a hypercholesterolemic (LDL receptor–null) background. The levels of 5-LO mRNA were reduced about 5-fold in a congenic strain, designated CON6, containing the resistant chromosome 6 region derived from the CAST/Ei strain (CAST), as compared with the background C57BL/6J (B6) strain. 5-LO protein levels were similarly reduced in the CON6 mice. Sequencing of the 5-LO cDNA revealed several differences between CON6 and the B6 strain. To test the whether 5-LO is responsible for the resistant phenotype, we bred a 5-LO knockout allele onto an LDL receptor–null (LDLR-/-) background. On this background, the mice bred poorly and only heterozygous 5-LO knockout mice were obtained. These mice showed a dramatic decrease (>26-fold; P<0.0005) in aortic lesion development, similar to the CON6 mice. Immunohistochemistry revealed that 5-LO was abundantly expressed in atherosclerotic lesions of apoE- /- and LDLR-/- deficient mice, appearing to colocalize with a subset of macrophages but not with all macrophage-staining regions. When bone marrow from 5-LO+/- mice was transplanted into LDLR-/-, there was a significant reduction in atherogenesis, suggesting that macrophage 5-LO is responsible, at least in part, for the effect on atherosclerosis. http://www.jlr.org/cgi/content/full/43/1/26 Induction of monocyte differentiation and foam cell formation in vitro by 7-ketocholesterol John M. Hayden1,a, Libuse Brachova1,a, Karen Higginsa, Lewis Obermillera, Alex Sevanianb, Srikrishna Khandrika2,a, and Peter D. Reavena Oxidized Cholesterol in Plasma Strong Predictor of Heart Attack Plasma Oxidized Low-Density Lipoprotein, a Strong Predictor for Acute Coronary Heart Disease Events in Apparently Healthy, Middle-Aged Men From the General Population Christa Meisinger, MD, MPH; Jens Baumert, MS; Natalie Khuseyinova, MD; Hannelore Loewel, MD; Wolfgang Koenig, MD Plasma oxLDL was the strongest predictor of CHD events compared with a conventional lipoprotein profile and other traditional risk factors for CHD. When both oxLDL and C-reactive protein were simultaneously assessed in the same model, they still predicted future CHD events even after multivariable adjustment. http://www.blackwell-synergy.com/doi/full/10.1111/j.1365-2796.2004.01402.x Journal of Internal Medicine 256 (5) , 413–420 K. Wallenfeldt, B. Fagerberg, J. Wikstrand, J. Hulthe (2004) Conclusions. These results provide new information, supporting the concept that circulating OxLDL was associated with the silent phase of atherosclerosis progression in clinically healthy men independently of conventional risk factors Measuring Oxidized LDL in Blood http://diabetes.diabetesjournals.org/cgi/content/full/53/4/1068 We concluded that the metabolic syndrome, a risk factor for CHD, is associated with higher levels of circulating oxLDL that are associated with a greater disposition to atherothrombotic coronary disease. Levels of oxLDL were measured (2000–2001) blindly at the Center for Experimental Surgery and Anesthesiology. An mAb-4E6-based competition enzyme-linked immunosorbent assay (ELISA) was used for measuring plasma oxLDL levels (5,16,17). The monoclonal antibody mAb-4E6 is directed against a conformational epitope in the apoB-100 moiety of LDL that is generated by substituting aldehydes for at least 60 lysine residues of apolipoprotein B-100. APO A1 and APO B Proteins http://en.wikipedia.org/wiki/Apolipoprotein_A1 Apolipoprotein A-I (ApoA-I) is an apolipoprotein. It is the major protein component of high density lipoprotein (HDL) in plasma. The protein promotes cholesterol efflux from tissues to the liver for excretion. It is a cofactor for lecithin cholesterol-acyl-transferase (LCAT) which is responsible for the formation of most plasma cholesteryl esters. http://en.wikipedia.org/wiki/Apolipoprotein_B Apolipoprotein B (APO APOB100 is found in lipoproteins originating from the liver (VLDL, IDL, LDL). Importantly, there is one APOB100 molecule per hepatic-derived lipoprotein. Hence, using that fact, one can quantify the number of lipoprotein particles by noting the total APOB100 concentration in the circulation. Since there is one and only one APOB100 per particle, the number of particles is reflected by the APOB100 concentration. The same technique can be applied to individual lipoprotein classes (e.g. LDL) and thereby enable one to count them as well. It is well established that APOB100 levels are associated with coronary heart disease, and are even a better predictor of it than is LDL level. A naive way of explaining this observation is to use the idea that APOB100 reflects lipoprotein particle number (independent of their cholesterol content). In this way, one can infer that the number of APOB100-containing lipoprotein particles is a determinant of atherosclerosis and heart disease. APO -E http://en.wikipedia.org/wiki/Apolipoprotein_E Experimental Biology and Medicine 230:40-48 (2005) https://content.nejm.org/cgi/content/full/349/17/1605 Stefan Blankenberg, M.D., Hans J. Rupprecht, M.D., Christoph Bickel, M.D., Michael Torzewski, M.D., Gerd Hafner, M.D., Laurence Tiret, Ph.D., Marek Smieja, M.D., Ph.D., François Cambien, M.D., Jürgen Meyer, M.D., Karl J. Lackner, M.D., for the AtheroGene Investigators Conclusions In patients with coronary artery disease, a low level of activity of red-cell glutathione peroxidase 1 is independently associated with an increased risk of cardiovascular events. Glutathione peroxidase 1 activity may have prognostic value in addition to that of traditional risk factors. Furthermore, increasing glutathione peroxidase 1 activity might lower the risk of cardiovascular events. J Am Coll Cardiol, 2006; 47:1005-1011, CLINICAL RESEARCH: ATHEROSCLEROSIS The Relationship Between Plasma Levels of Oxidized and Reduced Thiols and Early Atherosclerosis in Healthy Adults, Salman Ashfaq, MD, FACC*, Jerome L. Abramson, PhD, Dean P. Jones, PhD, Steven D. Rhodes, RN, William S. Weintraub, MD, FACC, W. Craig Hooper, PhD, Viola Vaccarino, MD, PhD, David G. Harrison, MD, FACC and Arshed A. Quyyumi, MD, FACC,* CONCLUSIONS: Glutathione redox state (Eh GSH/GSSG), an in vivo measure of intracellular oxidative stress, is an independent predictor for the presence of early atherosclerosis in an otherwise healthy population. This finding supports a role for oxidative stress in the pathogenesis of premature atherosclerosis, and its measurement may help in the early identification of asymptomatic subjects at risk of atherosclerotic disease. http://circ.ahajournals.org/cgi/content/full/100/22/2244 Circulation. 1999;100:2244. Background—Traditional risk factors account for only half of the morbidity and mortality from coronary heart disease (CHD). There is substantial evidence that oxidative injury plays a major role in the atherosclerotic process. Thus, antioxidants may protect against development of atherosclerosis. Glutathione, an intracellular tripeptide with antioxidant properties, may be protective. Prasad A, Andrews NP, Padder FA, et al. Glutathione reverses endothelial dysfunction and improves nitric oxide bioavailability. J Am Coll Cardiol 1999;34:507-514. Tim Guilford MD In Clinical Practice since 1981, Dr. Guilford was also Director of Biological Information System Clinical Laboratory specializing in Allergy and Immunology testing until 1993. His areas of medical interest include treatment of allergy, chronic illnesses and he uses Homeopathy and nutrient support for chronic illnesses. Over the last 10 years Dr. Guilford has become an expert in the role that glutathione plays in chronic illnesses. Glutathione decreases with age and chronic illnesses, and plays a key role in several systems that are critical for the maintenance of health. Low glutathione levels are associated with chronic inflammation, which prevents efficient immune function, and diminishes the ability to remove toxins. Dr. Guilford’s interest in glutathione has lead tp the formation of a liposomal glutathione product called ReadiSorb™ Glutathione. More information is available at www.Readisorb.com. The role of the 5-Lipoxygenase in atherosclerosis is particularly interesting. Atherosclerosis, a major cause of morbidity and mortality, is now seen as an inflammatory fibro-proliferative disease. Leukotriene receptors are abundantly expressed in atherosclerotic lesions in the aorta, heart and carotid artery. In fact the presence of high expression of 5-Lipoxygenase, correlates well with high plaque instability. Review of animal and human data suggest that 5-Lipoxygenase and its metabolites are up regulated in vessel walls, macrophages, dendritic cells, foam cells, mast cells, and neutrophils. Recent studies clearly have identified the 5-Lipoxygenase gene as a risk factor in such cardio vascular diseases as stroke and myocardial infarction. A survey of 470 subjects identified to have a gene variant leading to an increased expression of 5-Lipoxygenase demonstrated a significant increase in carotid artery intima-media thickness. Dietary intake of fish oils, which reduce the production of Leukotrienes, blunted the genotype effect. Another recent survey of subjects from Britain and Iceland, with higher than normal 5-Lipoxygenase expression, showed, double the usual rate of heart attacks. Mice genetically lacking the 5-Lipoxygenase gene showed a dramatic 26 fold reduction in aortic lesions. These studies suggest that 5-Lipoxygenase inhibition would be a valuable preventative measure in CV disease. Significantly increased urinary Leukotriene levels were found in patients following admission for acute myocardial infarction. Elevated levels of Leukotrienes were also found in patients with unstable angina. Leukotrienes are also involved in sickle cell disease and septic shock. Taken together these studies demonstrate that there is a significant benefit to treat patients suffering from ischemic injuries and the resulting organ damage by eliminating inflammatory events through 5-Lipoxygenase control. Recently, LT receptors have been shown to be expressed in the intimal hyperplasia of early atherosclerosis and in restenotic lesions after angioplasty. These findings emphasize the role that a 5-Lipoxygenase target could play in preventing restenosis after coronary interventions. Articles by Ross Rentea MD on Boswelia etc. http://www.lilipoh.com/articles/2006/winter/anthroposophical_aspects_of_diabetes_treatment.aspxAnthroposophical Aspects of Diabetes Treatment Author: Ross Rentea, M.D..Issue: LILIPOH #46 - Issue 11 Winter 2006 http://www.truebotanica.com/ http://www.frankincensegifts.com/ http://www.threekingsgifts.com/ http://www.wfu.edu/wfunews/2000/120400g.htm Boswellia References Department of Pharmacology and Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania Anon. Treatment of Crohn's disease with incense (Boswellia serrata extract). Arztezeitschrift fur Naturheilverfahren 2001;42:636. Mi-Kyung Chang, M.D., first author "Our study points out that CRP is not merely a marker of future cardiovascular events, as most people believe, but it actually binds to oxidized LDL and apoptotic or dying cells, giving it a potential role in development or modulation of atherosclerosis, as well as in other inflammatory disease," http://www.thirdage.com/ebsco/files/21509.html#ref40 http://www.glutathioneexperts.com/parkinsons.html http://www.glutathioneexperts.com/index.html It is a tripeptide composed of the amino acids glutamic acid, cysteine and glycine. Glutathione is found in all cells in the body, including the bile, the epithelial lining fluid of the lungs, and—at much smaller concentrations—in the blood. The highest concentration of glutathione is found in the liver, making it critically important in the detoxification and elimination of free radicals. Accumulation of these dangerous compounds can result in oxidative stress, which occurs when the generation of free radicals in the body exceeds the body’s ability to neutralize and eliminate them. Free radicals are highly reactive compounds created in the body during normal metabolic functions; they can also enter the body through the environment. http://www.drperlmutter.com/ Disclaimer click here: http://www.drdach.com/wst_page20.html The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician Also note that concerning an answer which appears as an electronically posted question, I am NOT creating a physician -- patient relationship. Although identities will remain confidential as much as possible, as I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur Finally, the material produced by myself may be reproduced for personal use, provided that appropriate credit is given; but this material may not be reprinted or reproduced in any format for any other purpose. (c) 2008 all rights reserved Jeffrey Dach MD, reproduction in any form prohibited without permission of author. Jeffrey Dach MD www.drdach.com disclaimer |
is the primary apolipoprotein of low density lipoproteins (LDL or "bad cholesterol"), which is responsible for carrying cholesterol to tissues. While it is unclear exactly what functional role APOB plays in LDL, it is the primary apolipoprotein component and is absolutely required for its formation. What is clear is that the APOB on the LDL particle acts as a ligand for LDL receptors in various cells throughout the body (i.e. less formally, APOB "unlocks" the doors to cells and thereby delivers cholesterol to them). Through a mechanism that is not fully understood, high levels of APOB can lead to plaques that cause heart disease (atherosclerosis). There is considerable evidence that levels of APOB are a better indicator of heart disease risk than total cholesterol or LDL. However, primarily for practical reasons, cholesterol, and more specifically, LDL-cholesterol, remains the primary lipid target and risk factor for atherosclerosis. 
Have you looked into the Young Living oils for Frankincense and Myrrh? They also have a "red" antioxidant drink called Ninja Red. The argument for oils is interesting-I would love you hear your thoughts.
Thank you for the time you spend educating. Sources like this site are truly the only way to health going forward. We all have the responsibility to educate ourselves to where health care in this Country falls short. Just look around at the young people dying of Cancer-and old persons disease. It is truly the Black Death of today and no one "gets" it. It is frightening that our medical community, for the most part, is looking the other way.
Thank You.
Christine Pica
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