Increase In Chondroitin Sulfate Research Articles

Increase in Chondroitin Sulfate and Decline in Arylsulfatase B May Contribute to Pathophysiology of COVID-19 Respiratory Failure

Introduction: The potential role of accumulation of chondroitin sulfates (CSs) in the pathobiology of COVID-19 has not been examined. Accumulation may occur by increased synthesis or by decline in activity of the enzyme arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) which requires oxygen for activity. Methods: Immunostaining of lung tissue from 28 patients who died due to COVID-19 infection was performed for CS, ARSB, and carbohydrate sulfotransferase (CHST)15. Measurements of mRNA expression of CHST15 and CHST11, sulfotransferase activity, and total sulfated glycosaminoglycans (GAGs) were determined in human vascular smooth muscle cells following angiotensin (Ang) II treatment. Results: CS immunostaining showed increase in intensity and distribution, and immunostaining of ARSB was diminished in COVID-19 compared to normal lung tissue. CHST15 immunostaining was prominent in vascular smooth muscle cells associated with diffuse alveolar damage due to COVID-19 or other causes. Expression of CHST15 and CHST11 which are required for synthesis of CSE and chondroitin 4-sulfate, total sulfated GAGs, and sulfotransferase activity was significantly increased following AngII exposure in vascular smooth muscle cells. Expression of Interleukin-6 (IL-6), a mediator of cytokine storm in COVID-19, was inversely associated with ARSB expression. Discussion/Conclusion: Decline in ARSB and resulting increases in CS may contribute to the pathobiology of COVID-19, as IL-6 does. Increased expression of CHSTs following activation of Ang-converting enzyme 2 may lead to buildup of CSs.

Specifi c features of connective tissuing metabolism of children with closed craniocerebral injury

The author of this paper, in order to diagnose the imbalance of connective tissue metabolism, has analyzed the results of laboratory tests of blood and urine according to biochemical parameters of the patients with closed craniocerebral injury (CCI) with diff erent severity and has established their clinical and diagnostic value. 100 children who had closed craniocerebral trauma were examined. There were 79 boys (79 %) and 21 girls (21 %), aged from 3 to 17 years among them. Distribution of children into groups was conducted according to the clinical forms of craniocerebral trauma: Group I — closed craniocerebral trauma, cerebral concussion — 50 children (50 %), average age (14,6 ± 2,5) years; Group II — closed craniocerebral trauma with cerebral contusion of moderate severity — 20 children (20 %), average age (13.5 ± 4.5 years); Group III —closed craniocerebral trauma with severe cerebral contusion — 30 children (30 %), average age (14.5 ± 3.5 years). Chondroitin sulfates were determined in the blood serum of patients — according to the М. Németh-Csóka method in the modifi cation of L. I. Slutskyi, fraction of glycosaminoglycans (GAG). The content of oxyproline was determined in the urine — by the reaction with chloramine-B, uronic acids — by the reaction with carbazole. In case of mild CCI (cerebral concussion), the indicators of biochemical studies of the blood and urine remained within the normal range, while with the increase in the severity of the injury, we observed an increase in chondroitin sulfate, and a decrease in the level of general GAG, its II and III fractions, and an increase in oxyproline in the urine, indicating the dysgenesia of the connective tissue metabolism and which may be the basis for the unfavorable course of closed craniocerebral injury of children during the rehabilitation period. Detection of changes in the connective tissue metabolism allows additionally predict the course of the disease in the period of rehabilitation and the possibility of recovery of children after CCI. Key words: children, craniocerebral injury, connective tissue dysgenesia, mucopolysaccharides, oxyproline.

Heparanase expression and glycosaminoglycans profile in renal cell carcinoma

A better understanding of the molecular mechanisms of renal cell carcinogenesis could contribute to a decrease in the mortality rate of this disease. The aim of this study was to evaluate the glycosaminoglycans profile and heparanase expression in renal cell carcinoma. The study included 24 patients submitted to nephrectomy with confirmed pathological diagnosis of renal cell carcinoma. The majority of the samples (87.5%) were classified in the initial stage of renal cell carcinoma (clinical stages I and II). Heparanase messenger ribonucleic acid expression was evaluated by quantitative real-time reverse transcription polymerase chain reaction, and sulfated glycosaminoglycans were identified and quantified by agarose gel electrophoresis of renal cell carcinoma samples or non-neoplastic tissues obtained from the same patients (control group). The sulfated glycosaminoglycans and hyaluronic acid were analyzed in urine samples of the patients before and after surgery. The data showed a significant statistical increase in chondroitin sulfate, and a decrease in heparan sulfate and dermatan sulfate present in neoplastic tissues compared with non-neoplastic tissues. Higher heparanase messenger ribonucleic acid expression in the neoplastic tissues was also shown, compared with the non-neoplastic tissues. The urine glycosaminoglycans profile showed no significant difference between renal cell carcinoma and control samples. Extracellular matrix changes observed in the present study clarify that heparanase is possibly involved with heparan sulfate turnover, and that heparanase and the glycosaminoglycans can modulate initial events of renal cell carcinoma development.

Oral hormonal contraceptives affect the concentration and composition of urinary glycosaminoglycans in young women

Urinary glycosaminoglycans (uGAG) have protective effects against urinary tract disorders. Here we investigated whether oral hormonal contraceptives (OC) affect uGAG excretion. Urine specimens were from young women regularly taking: ethinyl estradiol + drospirenone, n = 9; ethinyl estradiol + cyproterone acetate, n = 9; and ethinyl estradiol + gestodene, n = 7. Controls were from ten women not taking OC. Total uGAG was assayed as hexuronic acid/urinary creatinine. Sulfated uGAG species was determined by electrophoresis. Unlike controls, total uGAG in the two halves of the menstrual cycle was similar in the OC groups. Whole cycle uGAG was higher in the OC groups (p < 0.01), especially for ethinyl estradiol + cyproterone acetate (p < 0.005). The three OC produced decreases of approximately 50% in heparan sulfate (p < 0.02) and dermatan sulfate (p < 0.02), and a approximately 100% increase in chondroitin sulfate (p < 0.004). uGAG excretion is changed in women taking OC, and this might enhance the protective effects of these molecules against urinary tract disorders.

Pancreatic carcinoma is characterized by elevated content of hyaluronan and chondroitin sulfate with altered disaccharide composition

The amount and the types of glycosaminoglycans (GAGs) present in human pancreatic carcinoma were examined and compared with those in normal pancreas. Human pancreatic carcinoma contained increased levels (4-fold) of total GAGs. Particularly, this carcinoma is characterized by a 12-fold increase of hyaluronan (HA) and a 22-fold increase in chondroitin sulfate (CS) content. CS in pancreatic carcinoma exhibited an altered disaccharide composition which is associated with marked increase of non-sulfated and 6-sulfated disaccharides. Dermatan sulfate (DS) was also increased (1.5-fold) in carcinoma, whereas heparan sulfate (HS), the major GAG of normal pancreas, becomes the minor GAG in pancreatic carcinoma without significant changes in the content and in molecular size. In all cases, the galactosaminoglycans (GalGAGs, i.e. CS and DS) derived from pancreatic carcinomas were of lower molecular size compared to those from normal pancreas. The results in this study indicate, for the first time, that human pancreatic carcinoma is characterized by highly increased amounts of HA and of a structurally altered CS.

Thrombin adhesive properties: induction by plasmin and heparan sulfate.

We have previously demonstrated that chemically modified thrombin preparations induce endothelial cell (EC) adhesion, spreading and cytoskeletal reorganization via an Arg-Gly-Asp (RGD) sequence and the alpha v beta 3 integrin. Native thrombin, however, did not exhibit adhesive properties, consistent with crystal structure analysis, showing that Gly-Asp residues of the RGD epitope are buried within the molecule. We have now identified a possible physiological mean of converting thrombin to an adhesive protein. Plasmin, the major end product of the fibrinolytic system, converted thrombin to an adhesive protein for EC in a time and dose-dependent manner. EC adhesion and spreading was also induced by a low molecular weight (approximately 3,000 D) cleavage fragment generated upon incubation of thrombin with plasmin. Cell adhesion mediated by this fragment was completely inhibited by the synthetic peptide GRGDSP. Conversion of thrombin to an adhesive molecule was significantly enhanced in the presence of heparin or heparan sulfate, while other glycosaminoglycans (GAGs) (e.g., dermatan sulfate, keratan sulfate, chondroitin sulfate) had no effect. The role of cell surface heparan sulfate in thrombin conversion to EC adhesive protein was investigated using CHO cell mutants defective in various aspects of GAG synthesis. Incubation of both thrombin and a suboptimal amount of plasmin on the surface of formaldehyde fixed wild-type CHO-KI cells resulted in an efficient conversion of thrombin to an adhesive molecule, as indicated by subsequent induction of EC attachment. In contrast, there was no effect to incubation of thrombin and plasmin with fixed CHO mutant cells lacking both heparan sulfate and chondroitin sulfate, or with cells expressing no heparan sulfate and a three-fold increase in chondroitin sulfate. A similar gain of adhesive properties was obtained upon incubation of thrombin and plasmin in contact with native, but not heparinase-treated extracellular matrix (ECM) produced by cultured ECs. It appears that cell surface and ECM-associated heparan sulfate modulate thrombin adhesive properties through its heparin binding site in a manner that enables suboptimal amounts of plasmin to expose the RGD domain. Our results demonstrate, for the first time, a significant modulation of thrombin molecule by heparin, resulting in its conversion to a potent adhesive protein for ECs. This conversion is most effective in contact with cell surfaces, basement membranes and ECM.

Extracellular matrix changes in congenital hypertrophic pyloric stenosis

In pyloric stenosis, investigations of the histological pathology have concentrated on neuromuscular changes. These have shown a decrease in the innervation of the hypertrophied circular muscle and variable changes in the myenteric plexus. This study shows that the extracellular matrix (ECM) molecules have characteristic patterns in pyloric stenosis: chondroitin sulfate was markedly increased, with smaller increases in fibronectin and laminin. The increase in chondroitin sulfate was present in patients who were only several weeks old, with a short history, and in whom there was minimal circular muscle hypertrophy, and therefore was an early feature. It is not possible to ascribe aetiological significance to the increase in ECM molecules; nevertheless, the increase of chondroitin sulfate is the most likely explanation for the characteristic “cartilaginous” quality of the pyloric swelling.

Fibronectin, hyaluronan, and a hyaluronan binding protein contribute to increased ductus arteriosus smooth muscle cell migration

“Intimal cushions” which develop in the late gestation lamb ductus arteriosus (DA) are characterized by smooth muscle cells migrating into a large subendothelial space. Our previous in vitro studies, comparing DA cells with those from the aorta (Ao), have shown, even in early gestation, a 10-fold increase in DA endothelial incorporation of hyaluronan into the subendothelial matrix, a 2-fold increase in smooth muscle fibronectin synthesis and, in response to endothelial conditioned medium, a 2-fold increase in chondroitin sulfate. To determine whether these extracellular matrix components may be playing a role in inducing DA smooth muscle migration, we seeded DA or Ao smooth muscle cells onto three-dimensional collagen (2.0 mg/ml) gels and assessed migration 2, 5, and 8 days later. After 8 days, significantly greater numbers of DA compared to Ao cells were found invading the gels (23.1 ± 3.1% vs 16.2 ± 2.3% P < 0.01). Addition of GRGDS peptides (0.5 m M) or antibodies against fibronectin significantly decreased migration in the DA cells, but had no effect on migration in the Ao. Addition of endothelial conditioned medium to induce smooth muscle chondroitin sulfate production had no effect on DA cell migration. Inclusion of hyaluronan in the gel (0.5–1.5 mg), however, further enhanced DA cell migration, being greatest (31.9 ± 3.1%) at a concentration of 1 mg/ml. Hyaluronan was without effect on Ao smooth muscle cell migration. The ability of hyaluronan to promote migration in cultures of DA smooth muscle cells was blocked completely by the addition of antibodies (1:100 dilution, 1 μg/ml) to a cell surface hyaluronan binding protein (HABP). As well, addition of anti-HABP to cells on gels containing collagen only significantly reduced migration in the DA but not the Ao. Immunofluorescent staining revealed that in DA cells, HABP was more concentrated in lamellipodia and leading edges than in Ao cells. As well, DA smooth muscle cells synthesized greater amounts of HABP as determined by Western immunoblotting and immunoprecipitation using polyclonal antisera to HABP. Thus, our studies indicate that both increased fibronectin and HABP contribute to the enhanced migration of DA smooth muscle cells. These results, together with our previous studies showing a 10-fold increase in hyaluronan accumulation in the DA endothelial matrix, would suggest a mechanism for increased DA smooth muscle migration into the subendothelial matrix observed in vivo.

Transforming growth factor (type beta) promotes the addition of chondroitin sulfate chains to the cell surface proteoglycan (syndecan) of mouse mammary epithelia.

Cultured monolayers of NMuMG mouse mammary epithelial cells have augmented amounts of cell surface chondroitin sulfate glycosaminoglycan (GAG) when cultured in transforming growth factor-beta (TGF-beta), presumably because of increased synthesis on their cell surface proteoglycan (named syndecan), previously shown to contain chondroitin sulfate and heparan sulfate GAG. This increase occurs throughout the monolayer as shown using soluble thrombospondin as a binding probe. However, comparison of staining intensity of the GAG chains and syndecan core protein suggests variability among cells in the attachment of GAG chains to the core protein. Characterization of purified syndecan confirms the enhanced addition of chondroitin sulfate in TGF-beta: (a) radiosulfate incorporation into chondroitin sulfate is increased 6.2-fold in this proteoglycan fraction and heparan sulfate is increased 1.8-fold, despite no apparent increase in amount of core protein per cell, and (b) the size and density of the proteoglycan are increased, but reduced by removal of chondroitin sulfate. This is shown in part by treatment of the cells with 0.5 mM xyloside that blocks the chondroitin sulfate addition without affecting heparan sulfate. Higher xyloside concentrations block heparan sulfate as well and syndecan appears at the cell surface as core protein without GAG chains. The enhanced amount of GAG on syndecan is partly attributed to an increase in chain length. Whereas this accounts for the additional heparan sulfate synthesis, it is insufficient to explain the total increase in chondroitin sulfate; an approximately threefold increase in chondroitin sulfate chain addition occurs as well, confirmed by assessing chondroitin sulfate ABC lyase (ABCase)-generated chondroitin sulfate linkage stubs on the core protein. One of the effects of TGF-beta during embryonic tissue interactions is likely to be the enhanced synthesis of chondroitin sulfate chains on this cell surface proteoglycan.

Exogenous glycosaminoglycans modulate extracellular and intracellular accumulation of newly synthesized glycosaminoglycans by embryonic chick skin fibroblasts

The effects of exogenous glycosaminoglycans (GAG) on newly synthesized GAG accumulation in intra- and extra-cellular compartments of 17 incubation days chick embryonic skin fibroblasts have been examined. Exogenous GAG are able to act on both total GAG synthesis and secretion by embryonic fibroblasts and on the relative concentration of individual GAG. A decline in hyaluronic acid and an increase in chondroitin sulfate plus dermatan sulfate in the cellular compartment for all GAG administered have been detected. There was also similar behaviour in the extracellular compartment after sulfated GAG administration.

Proteoglycans and Hypertension: III: Aorta Proteoglycans in Dahl Salt-Sensitive Hypertensive Rats

The vascular proteoglycans probably have an important influence on the biomechanical properties of blood vessels and, therefore, may play a role in the development or maintenance of hypertension. In the aorta of the spontaneously hypertensive rat, the authors previously observed an increased content of chondroitin sulfate, an increased incorporation of [35S]sulfate into proteoglycans, and qualitative alterations in the [35S]polysaccharides compared to the normotensive Wistar Kyoto rat. To determine if these differences were related to hypertension or to strain variations, normotensive and hypertensive Dahl S rats were studied. There was a significant elevation (70%) in the aorta content of chondroitin sulfate, whereas the dermatan sulfate and hyaluronic acid contents were similar in the two groups. The in vitro incorporation of [35S]sulfate was increased 2.6-fold in the hypertensive animals. No differences between the two groups were observed with respect to the gel chromatographic profiles of the [35S]proteoglycans or the charge density of the [35S]glycosaminoglycans, as assessed by ion exchange chromatography. It was concluded that the increase in chondroitin sulfate and [35S]sulfate incorporation into proteoglycans occurred as a result of hypertension, regardless of genetic factors.

Heterogeneity of proteoglycans extracted before and after collagenase treatment of human articular cartilage. II. Variations in composition with age and tissue source.

Proteoglycans (A1 fractions) were extracted with 4M guanidine hydrochloride (GuHCl) from human articular cartilage samples of a wide age range. Distinctions were made between hip and knee, and upper and lower layers. The residues of these extractions were digested with purified collagenase, and a second extraction with 4M GuHCl was performed, which yielded appreciable amounts of proteoglycans. When proteoglycans from second extractions were compared with those from first extractions, the following changes were observed: an increase in chondroitin sulfate; a relative decrease in keratan sulfate; a decrease in protein content; and a decrease in the ratio of chondroitin 6-sulfate to chondroitin 4-sulfate. The same changes were found when nonaggregating proteoglycans were compared with proteoglycan aggregates, when proteoglycans from young cartilage were compared with those from mature cartilage, when proteoglycans from knee cartilage were compared with those from hip cartilage, and when proteoglycans from upper layers of cartilage were compared with those from deeper layers. It is suggested that the differences found between first and second extractions of cartilage, between upper and lower layers of cartilage, and between knee and hip cartilage are caused by variations in the relative amount of nonaggregating proteoglycans and/or variations in proteoglycan size.

Effects of hyperinsulinism and of diabetes on proteoglycans of the intervertebral disc in weanling sand rats.

Weanling sand rats (Psammomys obesus) develop hyperinsulinemia or diabetes or both, if fed a standard laboratory diet without a supplement of fiber rich salt bush. The annuli fibrosi of hyperinsulinemic or diabetic animals, which are still hyperinsulinemic, show a slight but statistically significant increase in chondroitin sulfate and a lesser, statistically nonsignificant increase in keratan sulfate. Possible causes of these changes are discussed and the likelihood of a role of hyperinsulinism in their production is pointed out.

Etude biochimique comparative des glycosaminoglycannes peptides du cartilage articulaire de la tete femorale humaine normale et arthrosique

Glycosaminoglycan peptides prepared by papain hydrolysis of different regions were obtained from osteoarthrotic and normal human femoral heads. Data obtained in these experiments show that in osteoarthrosis a decrease in keratan sulfate and an increase in chondroitin sulfate are observed. Since keratan sulfate appeared to play an important role in proteoglycan aggregation, we suggest that the keratan sulfate decrease is one of the factors involved in the cartilage disorder observed in patients suffering from osteoarthrosis.

Acidic glycosaminoglycans in urine, serum and myocardium of aged patients with myocardial infarction

The acidic glycosaminoglycans in urine, serum and myocardial tissue of aged patients with myocardial infarction have been analyzed by two-dimensional electrophoresis on cellulose acetate membranes in order to study the mechanism of repair of myocardium after infarction. Patients tested 4 years or more after infarction showed excretion of urinary glycosaminoglycans within the range normally encountered for the aged. However, in cases of acute myocardial infarction, the excretion of glycosaminoglycans was found to be increased 3 to 4 times in the early acute phase and then gradually to decrease to within the normal range during recovery. A significant increase in excretion of low sulfated chondroitin sulfate was observed in the acute phase. Low sulfated chondroitin sulfate was the major glycosaminoglycan in sera from the patients, regardless of stages. In normal myocardial tissue, hyaluronic acid was the major component and heparan sulfate, chondroitin sulfate and dermatan sulfate were the minor components. In myocardium from patients with acute infarction, a decrease in heparan sulfate was observed, while in that of old infarction, dermatan sulfate was the main component and in advanced aneurysm, increase in chondroitin sulfate was observed along with dermatan sulfate. These findings suggest that the repair process of infarcted myocardium is very similar to that occurring during healing of hepatic fibrosis and damaged arterial walls.

β-Aminopropionitrileと高コレステロール食投与によるラット大動脈コレステロールと酸性ムコ多糖体の変動

The concentration and composition of acidic glycosaminoglycans in rat aorta were examined using ion-exchange chromatography and chondroitinase method. The glycosaminoglycans from aorta of normal rats were identified chemically and these, in increasing order of concentration, were heparan sulfate, chondroitin sulfate B, chondroitin sulfate A, chondroitin sulfate C, and hyaluronic acid. Analysis of the glycosaminoglycan composition of aorta from young lathyritic rats revealed a marked increase in chondroitin sulfate, chondroitin sulfate B in particular, but essentially no change in other glycosaminoglycan components of the arterial wall except a decrease of heparan sulfate in the 4 week-treatment group. The relationship between the concentration and composition of acidic glycosaminoglycans and aortic cholesterol deposition was also examined. The concentration of aortic cholesterol in the three groups β-aminopropionitrile (βAPN, βAPN-high cholesterol, and high cholesterol groups) increased significantly compared to that of normal rats after 2 weeks of feeding, but the concentration of aortic cholesterol continued to show a significant increase only in lathyritic rats fed a high-cholesterol diet for 4 weeks. However, the accumulation of cholesterol in the aorta was not very striking. On the other hand, the concentration of glycosaminoglycans in lathyritic rats fed a high-cho1esterol diet showed a marked increase in heparan sulfate and chondroitin sulfate, having preventive effect for atherosclerosis. This finding would suggest that aortic glycosaminoglycans are preventive factors in the successive progress of atherosclerosis rather than factors responsible for initiation of atherosclerosis through their interaction with cholesterol.

Hepatic fibrosis—a study on hepatic collagen and acid mucopolysaccharide

Change of acid mucopolysaccharide in the liver was examined with relation to the collagen content during the process of the experimental hepatic damage of the rat liver. The possibility is suggested that chondroitin sulfate B is related to the progress of hepatic fibrosis. A consistency exists that the increase in chondroitin sulfate B and the activity concerning the synthesis and the degradation of acid mucopolysaccharide in the damaged liver.

Urinary protein and carbohydrate. 3. Age differences in acid mucopolysaccharides in human beings.

Summary1. Urinary acid mucopolysac-charide-glycopeptide fraction and its enzymic digest were fractionated on Dowex 1-X2 column, chloride form. The chemical composition of the eluates was determined. 2. The acid mucopolysaccharide-glycopeptide fraction of normal urine contains a mixture of acid mucopolysaccharide-glycopeptide complexes (70-80%) with a small amount of free acid mucopolysaccharide (20-30%). With increasing age, there were higher percentages of bound acid mucopolysaccharides and less free acid mucopolysaccharides in urine. 3. After enzymic digestion, there was an increase of chondroitin sulfate A or chondroitin sulfate C and a decrease in bound acid mucopolysaccharides in 0.5 M and 1.25 M NaCl eluates. With increasing age, a smaller proportion of the glycopeptides could be digested with a mixture of pronase, trypsin and papain. 4. In normal subjects, 60-90% of acid mucopolysaccharides are equally distributed between the 1.25 M and 1.5 M NaCl fraction. With increasing age, less acid mucopolysa...

Acid mucopolysaccharides of amyloid tissue

The acid mucopolysaccharides (MPS) were isolated from different organs from patients with primary and secondary amyloidosis, and the MPS composition of these tissues was compared with those isolated from control individuals. Although each organ contains different amounts and types of MPS, amyloid tissue in general shows an increase in total MPS, primarily due to heparitin sulfate. In the myocardium involved in primary (familial) amyloidosis (only one sample available for study), the increase in MPS is apparently due to hyaluronic acid, in contrast to liver, spleen, kidney, and heart tissue involved in secondary amyloidosis. A slight increase in chondroitin sulfate B was also noted in certain secondary amyloid tissues. The amino acid composition of peptide material bound to heparitin sulfate was determined, and no abnormality was observed from the similar MPS-protein complex isolated from control tissue.

ACID MUCOPOLYSACCHARIDES IN ATHEROSCLEROSIS.

Interest in the ground substance of vascular structures has been evoked by the advancement of histo-pathological studies on the atherosclerosis, emphasizing the possible role of mucopolysaccharide accumulation in the production of focal atheroma. Such histochemical observations on arterial mucopolysaccharide have stimulated the extension of the biochemical knowledge on their nature and metabolim. The questions were reviewed from the recent informations including some of our studies concerned. Our experiments at the first step were carried out on the gross aortic materials to overlook the changing pattern of total and fractionated AMPS with aging and atherosclerosis. At the next step, further microtechnique was introduced to permitting the analysis on the aortic material comprising as small as one intimal lesion, which was composed of the microscale extraction procedure including the selective precipitation with cation detergent and the densitometric determination of AMPS fractions after electrophoretic separation on cellulose acetate strip. The experiments have evidenced the facts that aging of aortic tissue appears to be characterized by a decline of total AMPS contents in aceton-dry tissue and a decrease in hyaluronic acid and chondroitinsulfate A or C content and an increase in chondroitinsulfate B, similarly to the aging skin or cartilage, and that the edematous lesions, perhaps an early phase of fibrous plaque, comprise both high AMPS value and hyaluronic acid content. The possible biological functions of AMPS on atherogenesis were also reviewed from the recent publications. AMPS was recognized to possess the properties of preventing thrombus formation and lipid deposition in the arterial wall through its antithrombin and lipid clearing activity and, on the other hand, those of inducing the fibrin and lipid deposit through physicochemical complex formation with fibrinogen and lipoprotein. The destruction or abnormal aggregation of AMPS in the ground substance might cause an increased permeability of the arterial wall to the circulating lipoprotein and also the destruction of connective tissue fibers, substantially inducing the atherosclerosis.