Changes in metabolism of connective tissue associated with ageing and arterio- or atherosclerosis

Hauss, W. H.; Junge-Hülsing, G; Hollander, Harry

doi:10.1016/s0368-1319(62)80052-0

Cited by 60 publications

(14 citation statements)

References 23 publications

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“…A remarkable series of investigations by Hauss et al in the 1960’s [ 110 , 111 ] measured the uptake of sulfur into sGAGs in the artery wall and its biological half-life as a function of age. Their studies revealed that the amount of sulfur that is taken up by the sGAGs is highest very early in life and decays exponentially over time, and that the retention cycle also decreases with age.…”

Section: Resultsmentioning

confidence: 99%

A novel hypothesis for atherosclerosis as a cholesterol sulfate deficiency syndrome

Seneff¹,

Davidson

Lauritzen

et al. 2015

Theor Biol Med Model

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BackgroundDespite a vast literature, atherosclerosis and the associated ischemia/reperfusion injuries remain today in many ways a mystery. Why do atheromatous plaques make and store a supply of cholesterol and sulfate within the major arteries supplying the heart? Why are treatment programs aimed to suppress certain myocardial infarction risk factors, such as elevated serum homocysteine and inflammation, generally counterproductive?MethodsOur methods are based on an extensive search of the literature in atherosclerotic cardiovascular disease as well as in the area of the unique properties of water, the role of biosulfates in the vascular wall, and the role of electromagnetic fields in vascular flow. Our investigation reveals a novel pathology linked to atherosclerosis that better explains the observed facts than the currently held popular view.ResultsWe propose a novel theory that atherosclerosis can best be explained as being due to cholesterol sulfate deficiency. Furthermore, atheromatous plaques replenish the supply of cholesterol and sulfate to the microvasculature, by exploiting the inflammatory agent superoxide to derive sulfate from homocysteine and other sulfur sources. We argue that the sulfate anions attached to the glycosaminoglycans in the glycocalyx are essential in maintaining the structured water that is crucial for vascular endothelial health and erythrocyte mobility through capillaries. Sulfate depletion leads to cholesterol accumulation in atheromas, because its transport through water-based media depends on sulfurylation. We show that streaming potential induces nitric oxide (NO) release, and NO derivatives break down the extracellular matrix, redistributing sulfate to the microvasculature. We argue that low (less negative) zeta potential due to insufficient sulfate anions leads to hypertension and thrombosis, because these responses can increase streaming potential and induce nitric-oxide mediated vascular relaxation, promoting oxygen delivery. Our hypothesis is a parsimonious explanation of multiple features of atherosclerotic cardiovascular disease.ConclusionsIf our interpretation is correct, then it would have a significant impact on how atherosclerosis is treated. We recommend a high intake of sulfur-containing foods as well as an avoidance of exposure to toxicants that may impair sulfate synthesis.

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Section: Resultsmentioning

confidence: 99%

A novel hypothesis for atherosclerosis as a cholesterol sulfate deficiency syndrome

Seneff¹,

Davidson

Lauritzen

et al. 2015

Theor Biol Med Model

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“…These observations suggest that the arterial pressure may influence the mucopolysaccharide content in the aorta by altering the rate of synthesis of the sulfated acid mucopolysaccharides. Studies on the turnover rate of acid mucopolysaccharides in the aorta (35) have shown that the maximal incorporation of radiosulfate into acid mucopolysaccharides occurs in about 24 hr after the administration of the sulfate and is significantly correlated with the turnover rate of the sulfated acid mucopolysaccharides.…”

Section: Discussionmentioning

confidence: 99%

Arterial wall metabolism in experimental hypertension of coarctation of the aorta of short duration

Hollander¹,

Kramsch²,

Farmelant³

et al. 1968

J. Clin. Invest.

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A B S T R A C T Coarctation of the mid-thoracic aorata was surgically produced in mongrel dogs which were sacrificed from 4-12 wk after the operation. As compared to the findings in control animals, the sodium, chloride, and water content of the hypetensive portion of the coarcted thoracic aorta was significantly elevated, whereas the electrolyte and water content of the relatively normotensive portion of the coarcted aorta was normal. The sodium, potassium, and water content of the pulmonary artery, skeletal muscle, and cardiac muscle of the coarcted dog was not altered. These observations suggest that an elevated arterial pressure may influence the electrolyte and water composition of the arteries.The arterial pressure also may influence the content and synthesis of acid mucopolysaccharides (MPS) in the arteries since the content of sulfated MPS and the incorporation of injected radiosulfate into sulfated MPS were significantly increased in, the hypertensive portion of the coarcted thoracic aorta but were significantly reduced in the relatively normotensive ("hypotensive") portion of the coarcted aorta. The observed increase in MPS may have been a factor directly responsible for the increase in the sodium content of the hypertensive aorta since MPS can act as polyelectrolytes and bind cations.Although the arterial pressure may influence certain metabolic functions in the arteries, it did

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“…This mechanism was suggested some time ago, although omitting subsequent neovascularization of coronary DIT [186-192]. However, the viewpoint that intimal cell proliferation is the beginning of atherosclerosis [186-192] was superseded by the currently endorsed hypothesis, which asserts that arterial intimal proliferation is an event secondary to lipid/macrophage penetration and inflammation [2,3,5,6,193]. Reflecting on the convenient hypothesis, the current classification of atherosclerosis excludes a variety of arterial pathologies characterized by intimal cell proliferation [194].…”

Section: Discussionmentioning

confidence: 99%

Neovascularization of coronary tunica intima (DIT) is the cause of coronary atherosclerosis. Lipoproteins invade coronary intima via neovascularization from adventitial vasa vasorum, but not from the arterial lumen: a hypothesis

Субботин

2012

Theor Biol Med Model

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Background An accepted hypothesis states that coronary atherosclerosis (CA) is initiated by endothelial dysfunction due to inflammation and high levels of LDL-C, followed by deposition of lipids and macrophages from the luminal blood into the arterial intima, resulting in plaque formation. The success of statins in preventing CA promised much for extended protection and effective therapeutics. However, stalled progress in pharmaceutical treatment gives a good reason to review logical properties of the hypothesis underlining our efforts, and to reconsider whether our perception of CA is consistent with facts about the normal and diseased coronary artery. Analysis To begin with, it must be noted that the normal coronary intima is not a single-layer endothelium covering a thin acellular compartment, as claimed in most publications, but always appears as a multi-layer cellular compartment, or diffuse intimal thickening (DIT), in which cells are arranged in many layers. If low density lipoprotein cholesterol (LDL-C) invades the DIT from the coronary lumen, the initial depositions ought to be most proximal to blood, i.e. in the inner DIT. The facts show that the opposite is true, and lipids are initially deposited in the outer DIT. This contradiction is resolved by observing that the normal DIT is always avascular, receiving nutrients by diffusion from the lumen, whereas in CA the outer DIT is always neovascularized from adventitial vasa vasorum . The proteoglycan biglycan, confined to the outer DIT in both normal and diseased coronary arteries, has high binding capacity for LDL-C. However, the normal DIT is avascular and biglycan-LDL-C interactions are prevented by diffusion distance and LDL-C size (20 nm), whereas in CA, biglycan in the outer DIT can extract lipoproteins by direct contact with the blood. These facts lead to the single simplest explanation of all observations: (1) lipid deposition is initially localized in the outer DIT; (2) CA often develops at high blood LDL-C levels; (3) apparent CA can develop at lowered blood LDL-C levels. This mechanism is not unique to the coronary artery: for instance, the normally avascular cornea accumulates lipoproteins after neovascularization, resulting in lipid keratopathy. Hypothesis Neovascularization of the normally avascular coronary DIT by permeable vasculature from the adventitial vasa vasorum is the cause of LDL deposition and CA. DIT enlargement, seen in early CA and aging, causes hypoxia of the outer DIT and induces neovascularization. According to this alternative proposal, coronary atherosclerosis is not related to inflammation and can occur in individuals with normal circulating levels of LDL, consistent with research findings.

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Changes in metabolism of connective tissue associated with ageing and arterio- or atherosclerosis

Cited by 60 publications

References 23 publications

A novel hypothesis for atherosclerosis as a cholesterol sulfate deficiency syndrome

A novel hypothesis for atherosclerosis as a cholesterol sulfate deficiency syndrome

Arterial wall metabolism in experimental hypertension of coarctation of the aorta of short duration

Neovascularization of coronary tunica intima (DIT) is the cause of coronary atherosclerosis. Lipoproteins invade coronary intima via neovascularization from adventitial vasa vasorum, but not from the arterial lumen: a hypothesis

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