Learn about symptoms, causes and treatment of heart disease, a term describing a wide range of conditions that can affect the heart. This chapter was designed to provide the reader with a brief overview of the current surgical treatment options for heart valve disease. Major topics of discussion. Heart Failure: Management and Prevention of Heart Failure Based on Current Understanding of Pathophysiological Mechanisms. Coronary artery disease (CAD), also known as ischemic heart disease (IHD), is a group of diseases that includes: stable angina, unstable angina, myocardial infarction. Original Article. Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes. Christopher P. Cannon, M.D., Eugene Braunwald, M.D., Carolyn H.Cholesterol Sulfate Deficiency and Coronary Heart Disease. Read the Flipbook and PDF Versions. Every article in the Journal, presented in PDF and Flip. Book, that you can save and read on any device, online and off, anytime. Get Both for $2. ARTICLE SUMMARY• Impaired sulfate supply to the heart is a key factor in cardiovascular disease.• Red blood cells, platelets and cells in the skin synthesize cholesterol sulfate catalyzed by sunlight.• Cholesterol sulfate, unlike cholesterol, is water soluble, so it can travel freely in the blood rather than packaged up inside an LDL particle.• Glyphosate, the active ingredient in the pervasive herbicide Roundup, disrupts sulfate synthesis in the skin and disrupts bile flow from the liver, leading to a systemic deficiency in cholesterol sulfate.• Sulfate provides negative charge in the blood vessel wall and for the red blood cells and platelets, promoting flow.• Sulfate also maintains the structured water that lines the vessel walls and presents a slick, frictionless surface to the red blood cells.• The atheroma actively recruits cholesterol to be ready to produce cholesterol sulfate when sulfate becomes available.• Inflammation, while damaging to surrounding tissues, performs a useful service by promoting an oxidative environment necessary to make sulfate.• A heart attack is a well- choreographed sequence of events aimed to restore sulfate supplies by oxidizing taurine, which is stored in large amounts in the heart.• Statin drugs, by reducing the supply of cholesterol sulfate to the heart, will lead to heart failure down the road, a worse prognosis than cardiovascular disease. Despite decades of research, atherosclerosis remains a poorly explained phenomenon. The simple story experts present to the public is that excess cholesterol accumulates in the blood and combines with other substances to form an atheroma (also called plaque) that lodges in the artery wall, eventually obstructing flow. Strikingly, however, the lipid deposits accumulate only in arteries and never in veins. Even more striking is the fact that the arteries supplying the heart are the most vulnerable. The conventional explanation leaves unanswered many questions about the pathogenesis of atherosclerosis and cardiovascular disease. Why does cardiovascular plaque accumulate only in arteries, and preferentially in arteries supplying the heart? What prompts the occurrence of inflammation, which many believe to be a critical factor in heart disease? Why have studies on vitamin D supplementation proved disappointing despite research showing a strong inverse relationship between sunlight availability and heart disease? To answer these questions, I propose a unifying theory for the etiology of cardiovascular disease. The theory involves cholesterol sulfate, a molecule that circulates in the bloodstream and performs a variety of important regulatory functions. I believe that the cause of heart disease is an inadequate supply of cholesterol sulfate to the heart. When there are pathologies that impair the normal conditions for making cholesterol sulfate, an atheroma develops as an alternative means of supplying the heart with vital cholesterol sulfate. When neither the normal nor back- up mechanisms are able to make adequate cholesterol sulfate, the outcome is heart failure, a much worse prognosis than atherosclerosis. A number of diverse observations involving various forms of sulfur support the hypothesis that impaired sulfur supply to the vasculature is the key factor in cardiovascular disease. For example, early studies on primates showed that a high- fat, high- cholesterol diet fed to monkeys (not a normal diet for them!) could induce atherosclerosis, but that simultaneous supplementation with sulfur- containing nutrients was protective. Similarly, experiments on rats showed that a diet supplemented with excess cholesterol, cholic acid (a bile acid) and vitamin D2 could induce aortic lesions expressing calcification and plaque formation, but it was possible to prevent such lesions completely through simultaneous supplementation with chondroitin sulfate (a modified sugar molecule containing oxidized sulfur). As another example, children with disorders in the metabolism of cysteine (a sulfur- containing amino acid) develop atherosclerosis- like arterial damage at an early age. Interestingly, the consumption of garlic—a rich source of sulfane sulfur—is inversely correlated with the progression of cardiovascular disease. Finally and remarkably, synthetic hydrogen sulfide donors (molecules that release therapeutic hydrogen sulfide) can protect mitochondria in endothelial cells (the thin layer of cells that line the interior of blood vessels) from oxidative damage. CHOLESTEROL SULFATE SYNTHESISNormally, keratinocytes (the predominant cells found in the epidermis), red blood cells (RBCs) and platelets produce cholesterol sulfate in the skin, catalyzed by sunlight. Therefore, in accordance with my unifying theory, one would expect sunny climates to reduce heart disease risk. Indeed, geographical data show an inverse relationship between cardiovascular disease and annual sunlight availability. France and Spain have much lower rates of death from heart attacks than the United Kingdom. In a study conducted in the British Isles, mean annual sunshine hours accounted for 4. Despite related studies showing that vitamin D deficiency is associated with cardiovascular disease risk,8 placebo- controlled trials have failed to demonstrate any benefit from vitamin D3 supplementation. Why? My coauthors and I suggest that, where heart disease is concerned, the benefit of sunlight comes from cholesterol sulfate synthesis rather than vitamin D3 synthesis. In a 2. 01. 2 article in Entropy,1. The enzyme that likely carries out this function is endothelial nitric oxide synthase (e. NOS), the same enzyme that produces nitric oxide to relax the artery wall. The enzyme e. NOS is a member of the cytochrome P4. CYP) superfamily of enzymes, which metabolize drugs and synthesize cholesterol, steroids and other lipids. I hypothesize that the overuse of sunscreen has played a dual damaging role, suppressing sunlight catalysis but also actively disrupting e. NOS’s sulfate- producing function due to sunscreen’s aluminum content. Many other environmental chemicals also disrupt CYP enzymes, including mercury. Roundup. When aluminum or other toxic chemicals disable e. NOS, it is unable to make enough sulfate to supply the needs of the endothelial cells, creating a systemic sulfate deficiency problem. It is well established that e. NOS produces superoxide as well as nitric oxide, but biologists have always viewed this as a pathology. At the same time, the fact that RBCs contain abundant e. NOS baffles biologists, because nitric oxide would disrupt hemoglobin’s ability to transport oxygen. Viewing e. NOS superoxide synthesis as an alternative function to oxidize sulfur offers an explanation for both of these puzzles. GLYPHOSATE AND HYPERLIPIDEMIAGetting back to coronary artery disease, most people assume that elevated serum lipids (hyperlipidemia) are a causal factor. Tens (if not hundreds) of millions of people receive advice from their doctor to take a statin drug to protect them from heart disease because their serum lipid levels are high. Therefore, one would expect a plot over time of the hospital discharge rates for hyperlipidemia to be highly correlated with a similar plot for coronary artery disease. This is not the case, however. As the figure below shows, the correlation coefficient value is a weak 0. Although correlation does not always imply causation, it is surprising and noteworthy when a factor presumed to be causative is not correlated with the disease. FIGURE 1: Graph of incidence of hospital discharge diagnoses of hyperlipidemia (ICD 2. ICD 4. 10- 4. 14) over time from 1. CDC. In comparison, there is a very strong and highly significant correlation between hyperlipidemia and glyphosate application to corn and soy crops (R = 0. Glyphosate application rates have steadily increased over time due to the widespread appearance of glyphosate- resistant weeds growing among the crops that are increasingly engineered to be Roundup Ready. Serum lipids have risen in tandem with the increase in glyphosate use, despite the increase in statin drug prescriptions. As the second figure suggests, it is not unreasonable to propose that glyphosate is causal in hyperlipidemia. Glyphosate disrupts CYP enzyme activity in the liver, which can explain the contribution of glyphosate to hyperlipidemia. A rat study assessing the impact of glyphosate, clofibrate (a cholesterol- lowering drug) and two phenoxyacid herbicides on liver function showed that glyphosate reduced the activity of CYP enzymes in the liver much more than the other substances investigated. Multiple CYP enzymes are needed to produce bile acids,2. Bile acids normally export a large amount of cholesterol via the digestive system. Impeded bile acid synthesis due to a defective CYP7. A1 gene produced neonatal cholestasis (blocked bile ducts) and hypercholesterolemia (specifically, elevation in serum LDL) in mice fed a normal chow diet. Given that e. NOS is a CYP enzyme, it is entirely plausible that glyphosate disrupts e. NOS’s ability to synthesize sulfate. We would expect e. NOS exposure to glyphosate in the red blood cells, because glyphosate export via the kidney requires transit through the vasculature. Disrupted synthesis of cholesterol sulfate will necessitate an increase in the synthesis of LDL particles to transport cholesterol in its unsulfated form, because cholesterol is not water- soluble and therefore must be stored inside a lipid particle for transport. ATHEROMA AS ALTERNATIVE SUPPLIER OF CHOLESTEROL SULFATEIn another Entropy publication, my coauthor and I suggested that when red blood cells produce cholesterol sulfate while traversing the surface veins, catalyzed by sunlight, they release the cholesterol sulfate to the tissues in the capillaries.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. Archives
November 2017
Categories |