Troglitazone inhibits alpha1-adrenoceptor-induced DNA synthesis in vascular smooth muscle cells.

While vascular smooth muscle cell proliferation is important in hypertension, relatively little is known about the contribution of catecholamines. Novel insulin sensitizing agents, thiazolidinediones, have been demonstrated to inhibit angiotensin II-, basic fibroblast growth factor (FGF)-induced growth of vascular smooth muscle cells. We hypothesize that these agents might also inhibit the effect of the stimulation of alpha1-adrenoreceptors on the proliferation of vascular smooth muscle cells. Troglitazone (1-20 microM), a member of the thiazolidinediones, significantly inhibited the stimulation of alpha1-adrenoreceptor-induced DNA synthesis, c-fos induction and mitogen-activated protein (MAP)-kinase activation. This effect was associated with inhibition by troglitazone of the transactivation of the serum response element (SRE), which regulates c-fos expression. Inhibition of c-fos induction by troglitazone appeared to occur via blockade of the upstream of MAP kinase activation in vascular smooth muscle cells. At this dose, troglitazone inhibited the ternary complex factor (TCF)-dependent activation, which is regulated by MAP kinase activation, but did not inhibit the TCF-independent SRE activation. Besides, the degree of the inhibitory effect of troglitazone on MAP kinase activation, DNA synthesis, c-fos expression differs. This may show that troglitazone work on multiple sites. These results suggest that troglitazone is a potent inhibitor of vascular smooth muscle cells proliferation through the downregulation of c-fos expression and may be a useful agent for prevention of atherosclerosis which is a result of hypertension.     

Gene expression profiles in response to the activation of adrenoceptors in A7r5 aortic smooth muscle cells

1. Vascular adrenoceptors play an important role in vascular physiology and pathophysiology, such as hypertension, atherosclerosis and restenosis after angioplasty. To define the changes in the ene expression in vascular smooth muscle cells in response to the activation of alpha1- or beta-adrenoceptors, a DNA microarray was used. 2. First, the existence of alpha1- and beta-adrenoceptors in A7r5 aortic smooth muscle cells was confirmed by radioligand binding. Then, the inhibitory effects of phenylephrine (an alpha1-adrenoceptor agonist) and isoproterenol (a beta-adrenoceptor agonist) on the proliferation of A7r5 cells were determined by [3H]-thymidine incorporation. 3. The A7r5 cells were treated with 10 micromol/L phenylephrine or 1 micromol/L isoproterenol for 24 h and changes in gene expression were detected with the DNA microarray. Only 14 and 20 genes were identified after treatment of cells with phenylephrine and isoproterenol, respectively, and most genes displayed decreased expression. The changed genes could be grouped into five major functional categories: cell signalling/communication, cell structure/motility, cell/organism defence, gene/protein expression and metabolism. The gene expression profile in response to the activation of alpha1-adrenoceptors was very different from that following activation of beta-adrenoceptors. Interestingly, many phenylephrine-responsive genes were associated with metabolism, whereas many isoproterenol-responsive genes encoded cell signalling and structure proteins. This means that adrenoceptors may modulate multiple aspects of biological function in vascular smooth muscle cells. 4. Collectively, the activation of both alpha1-adrenoceptors (with phenylephrine) and beta-adrenoceptors (with isoproterenol) inhibited the proliferation of A7r5 cells, but microarray data revealed that the mechanisms may be different: the activation of alpha1-adrenoceptors could induce the expression of metabolic genes, resulting in the inhibition of proliferation, whereas activation of beta-adrenoceptors altered the expression of genes that encoded cell signalling and structure proteins to inhibit cell proliferation.     

Valsartan inhibits angiotensin II-stimulated proliferation of smooth muscle cells from human coronary artery.

OBJECTIVES: Angiotensin II is involved in the pathogenesis of atherosclerosis by inducing hyperproliferation of vascular smooth muscle cells. Little is known whether the sartans can inhibit the angiotensin-stimulated proliferation of smooth muscle cells. METHOD: The effect of valsartan on the angiotensin II-stimulated proliferation of smooth muscle cells from human coronary artery was investigated. RESULTS: Angiotensin II significantly increased cell proliferation by about 30% at a concentration of 10(-6) M without significant changes at the lower concentrations 10(-7) and 10(-8) M. Valsartan at the dosages 10(-8) to 10(-6) M had no effect on serum-stimulated proliferation. Valsartan at the dosages 10(-6) and 10(-7) M inhibited the cell proliferation induced by 10(-6) M angiotensin. CONCLUSION: Valsartan may prevent atherosclerosis by inhibiting angiotensin-induced vascular smooth muscle cell proliferation.     

Inhibition of human pulmonary artery smooth muscle cell proliferation and migration by sabiporide, a new specific NHE-1 inhibitor

Abnormal growth of vascular smooth muscle cells is seen in various pathological conditions such as hypertension, atherosclerosis, and restenosis. Na/H exchanger (NHE) activation appears to play a permissive role in vascular smooth muscle cell proliferation and vascular remodeling. The present study investigated the effect of a new specific NHE-1 inhibitor, sabiporide, on human pulmonary artery smooth muscle cell proliferation and migration. Concentrations of sabiporide as low as 20 micromol/L in the culture medium containing growth factors inhibited cell proliferation, as measured by cell counting, and also inhibited the rate of DNA synthesis, as examined by measuring BrdU incorporation into DNA. Cell growth inhibition was not caused by cell death, as demonstrated by the measurement of intracellular lactate dehydrogenase release and by the reversibility of inhibition upon washing. By fluorescent-activated cell sorting analysis, we are the first to demonstrate that NHE-1 inhibition arrests the cell cycle progression at G0/G1 phase, suggesting that NHE activation plays a permissive role in entrance of cells into the cell cycle. Sabiporide also concentration-dependently inhibited human pulmonary artery smooth muscle cell migration. The present study showed that sabiporide inhibits vascular smooth muscle cell proliferation and migration by blocking the cell cycle progression at G0/G1 phase.     

Inhibitory effect of curcumin, an anti-inflammatory agent, on vascular smooth muscle cell proliferation.

The effects of curcumin, an anti-inflammatory agent from Curcuma longa, on the proliferation of blood mononuclear cells and vascular smooth muscle cells were studied. Proliferative responses were determined from the uptake of tritiated thymidine. In human peripheral blood mononuclear cells, curcumin dose dependently inhibited the responses to phytohemagglutinin and mixed lymphocyte reaction at the dose ranges of 10(-6) to 3 x 10(-5) and 3 x 10(-6) to 3 x 10(-5) M, respectively. Curcumin (10(-6) to 10(-4) M) dose dependently inhibited the proliferation of rabbit vascular smooth muscle cells stimulated by fetal calf serum. Curcumin had a greater inhibitory effect on platelet-derived growth factor-stimulated proliferation than on serum-stimulated proliferation. Cinnamic acid, coumaric acid and ferulic acid were much less effective than curcumin as inhibitors of serum-induced smooth muscle cell proliferation, suggesting that the cinnamic acid and ferulic acid moieties alone are not sufficient for activity, and that the characteristics of the diferuloylmethane molecule itself are necessary for activity. Curcumin may be useful as a new template for the development of better remedies for the prevention of the pathological changes of atherosclerosis and restenosis.     

Inhibitory effects of docetaxel on platelet-derived growth factor (PDGF)-BB-induced proliferation of vascular smooth muscle cells through blocking PDGF-receptor β phosphorylation

The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial wall is an important pathogenic factor for vascular disorders such as atherosclerosis and restenosis after angioplasty. The present study was designed to investigate the inhibitory effects of docetaxel on VSMC proliferation, as well as the molecular mechanism of this inhibition. Docetaxel at 10, 20 and 40 μM significantly inhibited both the proliferation and the DNA synthesis of fetal bovine serum (FBS)- and platelet-derived growth factor (PDGF)-BB-stimulated VSMCs in a concentration-dependent manner. In accordance with these findings, docetaxel blocked the FBS- and PDGF-BB-induced progression of synchronized cells through the G0/G1 phase of the cell cycle. Docetaxel also decreased the expressions of cell cycle-related proteins, including cyclin-dependent kinase (CDK) 2, cyclin E, CDK4, cyclin D1, retinoblastoma protein, and proliferative cell nuclear antigen in PDGF-BB-stimulated VSMCs. Docetaxel significantly inhibited the phosphorylation of extracellular signal-regulated kinase 1/2, Akt, and phospholipase C-γ1, downstream molecule in the PDGF-BB signaling pathway. Docetaxel suppressed the phosphorylation of PDGF receptor (PDGF-R) β, the upstream molecule in PDGF-BB signaling cascade, suggesting that the inhibitory effect of docetaxel on the proliferation of VSMCs may occur by blocking PDGF-Rβ phosphorylation. Thus, docetaxel may be a potential antiproliferative agent for the treatment of atherosclerosis and angioplasty restenosis.[Supplementary Figures: available only at http://dx.doi.org/10.1254/jphs.10276FP].     

Mechanism of dipyridamole's action in inhibition of venous and arterial smooth muscle cell proliferation

Dipyridamole is a potential pharmacological agent to prevent vascular stenosis because of its antiproliferative properties. The mechanisms by which dipyridamole inhibits the growth of vascular smooth muscle cells, especially venous smooth muscle cells, are unclear. In the present study, dipyridamole transiently but significantly increased cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels in human venous and arterial smooth muscle cells in a time- and dose-dependent manner. Peak concentrations of both cyclic nucleotides were achieved at 15-30 min. and correlated with inhibition of proliferation in both cell types. The antiproliferative effects of dipyridamole observed at 48 hr were similar whether drug exposure was only 15 min. or sustained for 48 hr. Specific competitive inhibitors of protein kinases A and G attenuated the antiproliferative effects of subsaturating concentrations of dipyridamole, with the effects of protein kinase inhibition being particularly pronounced in venous smooth muscle cells. Flow cytometry analysis showed that dipyridamole caused an enrichment of cells in G(0)/G(1) and a corresponding reduction of cells in S phase. These data indicate that a transient increase in cGMP and cAMP is sufficient to induce downstream kinase activation and subsequent cell cycle arrest, and that protein kinase G may be more important than protein kinase A in mediating the growth inhibitory effect of dipyridamole in venous protein kinase.     

Effect of heparin-like compounds on the in vitro proliferation and protein synthesis of various cell types

Previous studies have shown that heparin and heparin-like compounds inhibit the proliferation of arterial smooth muscle cells (SMC) both in vivo and in vitro. This anti-proliferative effect seems to be exerted almost exclusively on arterial SMC and related cell types. In the present study the effect of heparin (HTh) is compared with that of two sulfated glycosaminoglycans with low anticoagulant activity, sulodexide (SDX) and low molecular weight heparin (OP/LMWH) on cell proliferation and protein synthesis of 3 cell types: human arterial smooth muscle cells (SMC), fibroblast-like cells (BHK-21) and epithelial cells (rat hepatoma cells, FAO). HTh, SDX and OP/LMWH (5-100 micrograms/ml) are equally effective in reducing the proliferation of human arterial SMC. This inhibition is dose dependent and reversible. BHK-21 and FAO cells are even more sensitive than SMC to heparin-like compounds. For example 1 microgram/ml of heparin-like compounds is sufficient to produce 40-60% inhibition of FAO cell proliferation. In all types of cells HTh, SDX and OP/LMWH do not reduce the incorporation of 35S-methionine into cellular and medium proteins; they increase the radioactivity incorporated into some proteins secreted into the medium. In the case of SMC this effect is dependent on the concentration and the length of exposure to heparin-like compounds. These findings demonstrate that several cell types are sensitive to the anti-proliferative effect of heparin-like compounds.     

Endothelium-independent vasorelaxation by ticlopidine and clopidogrel in rat caudal artery

Objectives Thienopyridines are prodrugs currently used as anti‐aggregating agents. The aim of this study was to determine if these compounds might have vascular activity independent of hepatic bioactivation. Methods The direct activity of thienopyridines was studied in rat caudal arterial rings and aortic smooth muscle cells in culture. Key findings Both compounds (0.01 µm –100 µm ) showed a concentration‐dependent vasorelaxation in arterial tissues precontracted with phenylephrine, 5‐hydroxytryptamine and KCl. The relaxation induced by 100 µm ticlopidine and clopidogrel was greater than 80%. The relaxation by ticlopidine was compared with the activity of acetylcholine. These two agents showed similar potency, although ticlopidine was slightly more active. Pretreatment with the nitric oxide synthase inhibitor L‐NAME inhibited the relaxation by acetylcholine but not that by ticlopidine. To further study vasorelaxation by ticlopidine, other pharmacological inhibitors including propranolol, nifedipine and suramin were used. These compounds lacked inhibitory effects on the vasorelaxation by ticlopidine. In vascular smooth muscle cells, 1 µm ticlopidine induced a decrease in cell proliferation, while incubation with both ticlopidine and ADP or 2‐methioADP led to an additive effect. Conclusions The data suggest that ticlopidine and clopidogrel cause relaxation of arterial tissues and influence vascular smooth muscle cell proliferation directly without hepatic biotransformation. Furthermore, the arterial relaxation induced in vitro by thienopyridines is endothelium independent, and β‐adrenergic and P2 receptors are not involved.     

Inhibitory effect of pentalenolactone on vascular smooth muscle cell proliferation

The effect of pentalenolactone, an inhibitor of glyceraldehyde-3-phosphate dehydrogenase, on rat vascular smooth muscle cell proliferation was studied. Addition of pentalenolactone together with serum to quiescent cells dose-dependently inhibited cell proliferation and DNA synthesis. This inhibition was not associated with cell death. When quiescent cells were stimulated with serum and then treated with pentalenolactone, the inhibitory effect on the DNA synthesis declined gradually. A similar result was obtained when PD 98059 (2'-amino-3'-methoxyflavone), an inhibitor of extracellular signal-regulated kinase1/2 (ERK1/2) kinase (MEK1/2), was added to the cells after serum stimulation. Pentalenolactone inhibited serum or protein kinase C activator (phorbol 12,13-dibutyrate)-induced phosphorylation of ERK1/2 and MEK1/2. In contrast, pentalenolactone had little effect on platelet-derived growth factor receptor autophosphorylation. Taken together, these results indicate that pentalenolactone inhibits vascular smooth muscle cell proliferation, and that this inhibition appears to be mediated by inhibition of the ERK1/2 cascade.     

Astrapterocarpan isolated from Astragalus membranaceus inhibits proliferation of vascular smooth muscle cells

The inhibitory effects of astrapterocarpan, formononetin, and calycosin isolated from Astragalus membraneceus on platelet-derived growth factor (PDGF)-BB-induced proliferative response in rat vascular smooth muscle cells (A10 cells) were investigated. Astrapterocarpan significantly inhibited PDGF-BB-induced cell proliferation and DNA synthesis in a concentration-dependent manner. This inhibition was not attributed to toxicity. In contrast, formononetin and calycosin had no effect. We next examined the effect of astrapterocarpan on PDGF-BB signal transduction. Astrapterocarpan inhibited PDGF-BB-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERIC1/2) mitogen-activated protein (MAP) kinase. However, this compound had no effect on phosphorylation of PDGF-beta-receptor, Akt kinase and p38 MAP kinase. These results indicated that astrapterocarpan inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and that this effect may be mediated, at least in part, by inhibition of the ERK1/2 MAP kinase cascade.     

丹皮酚对动脉粥样硬化家兔血管平滑肌细胞增殖的影响

目的研究丹皮酚对动脉粥样硬化家兔血管平滑肌细胞增殖的影响。方法高脂饮食法复制家兔动脉粥样硬化病理模型;HE染色并光镜观察主动脉病理学改变;MTT法分析体外培养的兔血管平滑肌细胞增殖水平;全自动生化分析仪测定主动脉组织中脂质含量;酶法测定SOD、MDA含量;放射免疫分析法测定IL-1β、TNF-α的含量;免疫组织化学法检测主动脉组织中PCNA的蛋白表达。结果丹皮酚(75、150 mg.kg-1)治疗给药(ig,6 wk)能减轻模型动物主动脉内膜增厚及泡沫细胞数量;使主动脉组织中脂质、脂质过氧化反应以及炎性细胞因子含量等方面得到显著改善;并能显著抑制主动脉组织中PCNA蛋白的表达强度;丹皮酚(100~300 mg.L-1)可明显抑制体外培养的血管平滑肌细胞增殖反应。结论丹皮酚对血管平滑肌细胞增殖有明显抑制作用,可能是其降脂、减轻脂质过氧化反应以及炎性细胞因子含量等协同作用结果,并可能通过抑制PCNA的表达而调控动脉粥样硬化病变中的血管平滑肌细胞增殖周期。     

Clitocybin B inhibits rat aortic smooth muscle cell proliferation through suppressing PDGF-Rβ phosphorylation

The increased proliferation of vascular smooth muscle cells (VSMCs) in the arterial wall is a critical pathogenic factor for vascular diseases such as atherosclerosis and restenosis after angioplasty. Clitocybin B was reported to have either a potent free radical scavenging effect or effects that were isolated from the culture broth of mushroom Clitocybe aurantiaca. The present study was designed to investigate the effects of clitocybin B on VSMC proliferation and its possible molecular mechanism. Clitocybin B significantly inhibited the proliferation and the DNA synthesis of PDGF-BB-stimulated VSMCs in a concentration-dependent manner. In agreement with these findings, clitocybin B suppressed the PDGF-BB-induced progression through G0/G1 to S phase of cell cycle. Clitocybin B also down-regulated the expressions of cell cycle-related proteins, including cyclin-dependent kinase (CDK)2, cyclin E, CDK4, cyclin D1, and proliferative cell nuclear antigen in PDGF-BB-stimulated VSMCs. Clitocybin B significantly inhibited the phosphorylation of Akt, extracellular signal-regulated kinase 1/2, and phospholipase C-γ1, in the PDGF-BB signaling pathway. Clitocybin B suppressed the PDGF-Rβ activation in PDGF-BB signaling cascade. These results suggested that the inhibitory effect of clitocybin B on the proliferation of VSMCs may be associated with suppressing PDGF-Rβ phosphorylation. Thus, clitocybin B may be an effective antiproliferative agent for the prevention of atherosclerosis and restenosis.     

动脉粥样硬化血管内皮分泌功能失调与平滑肌细胞增殖

血管内皮细胞和平滑肌细胞是血管壁两种主要细胞,两者在结构上和功能上有着密切的关系,动脉粥样硬化的发生源于循环因子和血管壁细胞间的相互作用,内皮细胞损伤等所导致的分泌功能失调和平滑肌细胞的异常增殖而引起的血管腔狭窄和痉挛是动脉粥样硬化等多种血管疾病发生发展的共同病理基础。本文从动脉粥样硬化病理状态下血管内皮分泌的生长因子、细胞因子、血管活性物质对平滑肌细胞增殖影响的最新研究进展做一综述。     

Phytoestrogen derivatives differentially inhibit arterial neointimal proliferation in a mouse model

Neointimal proliferation is a key element in atherosclerotic plaque formation and in arterial restenosis following angioplasty. Estrogen-like compounds, including naturally occurring plant phytoestrogens, are known to alter the extent of neointimal proliferation. This study investigates the anti-atherogenic/restenotic effect of several synthetic metabolites of isoflavone phytoestrogens (dihydrodaidzein, tetrahydrodaidzein and dehydroequol) (Novogen, Sydney, Australia). Acute neointimal proliferation was induced in the iliac artery of cholesterol-fed mice, by mechanically damaging the endothelium. Phytoestrogens were administered orally for 4 weeks and the damaged arteries harvested. Intimal area, as a percentage of the iliac artery wall area, was measured. Dihydrodaidzein significantly halved the intimal response (intima approximately 25% of wall area; p < 0.01) compared with placebo diet-fed mice (intima approximately 50% of wall area), while tetrahydrodaidzein and dehydroequol showed no inhibitory effects. Immunohistochemistry demonstrated that alpha-actin-positive vascular smooth muscle cells were the major cell type in the proliferating neointima. A single layer of endothelium covered the thickened intima by 4 weeks. Thus, a specific phytoestrogen isoflavone compound (dihydrodaidzein) can selectively inhibit neointimal proliferation, either by inhibition of vascular smooth muscle cell migration and proliferation, and/or by enhancing endothelial proliferation and function, and inhibition of endothelial apoptosis.     

Effect of vitamin E on the development of atherosclerosis

The development of atherosclerosis is a multifactorial process in which both elevated plasma cholesterol levels and proliferation of smooth muscle cells play a central role. Numerous studies have suggested the involvement of oxidative processes in the pathogenesis of atherosclerosis and especially of oxidised low density lipoproteins. Some epidemiological studies have shown an association between high dietary intake or high serum concentrations of vitamin E and lower rates of ischemic heart disease. Recently, the Cambridge Heart Antioxidant Study (CHAOS) reported strong protection by high vitamin E doses against the risk of fatal and non fatal myocardial infarction. Here we have shown that incubation of vascular smooth muscle cells in the presence of alpha-tocopherol resulted in inhibition of cell proliferation and protein kinase C activity. Since beta-tocopherol and probucol are not inhibitory, the effect of alpha-tocopherol is considered due to a non-oxidant mechanism. In order to understand the protective role of alpha-tocopherol against atherosclerosis in vivo the following rabbit studies were carried out. Atherosclerosis was induced by a vitamin E poor diet containing 2% cholesterol in a group of rabbit. The other groups had 2% cholesterol in the diet plus 50 mg/kg vitamin E i.m. or 1% probucol or 50 mg/kg vitamin E plus 1% probucol. After 4 weeks, aortas were removed and analysed by microscopy for atherosclerotic lesions. Samples of the media were analysed for protein kinase C activity. The aortas of cholesterol-fed rabbits showed typical atherosclerotic lesions, detected by microscopic examination, their media smooth muscle cells exhibited an increase in protein kinase C activity. Vitamin E fully prevented cholesterol induced atherosclerotic lesions and the induction of protein kinase C activity while probucol was not effective. These results show that the protective effect of vitamin E against hypercholesterolemic atherosclerosis is not produced by an other antioxidant such as probucol and, therefore, may not be linked to the antioxidant properties of this vitamin. The effects observed at the level of smooth muscle cells in vitro and ex-vivo suggests an involvement of signal transduction events in the protective effect of vitamin E against atherosclerosis.     

Effects of the selective COX-2 inhibitors celecoxib and rofecoxib on human vascular cells

Rheumatoid arthritis (RA) is associated with a reduced life expectancy considered to be partly caused by cardiovascular events. A growing concern is that accelerated atherosclerosis is driven by inflammatory mechanisms similar to those responsible for RA. Therefore, selective COX-2 inhibitors, which are widely used for the symptomatic treatment of pain and inflammation in RA, may have an impact on atherosclerotic processes. Their anti-inflammatory properties might provoke anti-atherogenic effects but on the other hand, selective inhibition of anti-thrombotic prostacyclin and COX-2 independent effects might promote the risk of increased prothrombotic activity. In the current study, the effects of the presently marketed selective COX-2 inhibitors celecoxib and rofecoxib on vascular cells have been investigated. Celecoxib inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner. At high concentrations, it induced apoptosis and the modulation of inhibitory cell cycle proteins. In contrast rofecoxib-even at high concentrations-had no effect on cell proliferation, apoptosis or cell cycle distribution indicating that celecoxib and rofecoxib do not affect the same signal transduction pathways in endothelial cells. Both drugs did not affect apoptosis induction or cell cycle proliferation in human vascular smooth muscle cells. The observed effects on endothelial cells appear to be COX-independent since both drugs selectively inhibited COX-2-activity and the applied concentrations lay beyond the IC(50) for inhibition of prostacyclin production. Regarding endothelial apoptosis as a relevant event in the initiation and progression of atherosclerosis the present data put forward the hypothesis that the presently marketed COX-2 inhibitors have a different impact on atherosclerotic processes.     

硫酸多糖与动脉粥样硬化

动脉粥样硬化（ＡＳ）的发生、发展是一个十分复杂的病理过程。它涉及到血管内皮细胞（ＥＣ）、平滑肌细胞（ＳＭＣ）、炎性细胞（如单核细胞、巨噬细胞等）、淋巴细胞、血小板等多种细胞及相关细胞因子。许多研究发现硫酸多糖与ＡＳ存在密切的关系。大多报道表明硫酸多糖可保护ＥＣ免受各种刺激因子的损伤作用,从而阻断ＡＳ形成的起始环节;另外,硫酸多糖也可通过抑制ＶＳＭＣ增殖、迁移;减少炎性细胞、淋巴细胞、血小板等粘附、聚集到血管内膜;抑制补体的激活等多种途径来达到抗ＡＳ目的。但也有文献报道部分硫酸多糖反而促进ＡＳ形成。而且硫酸多糖的抗ＡＳ活性与其分子结构有关,所以ＡＳ与硫酸多糖的关系是一直存在争议的问题。     

In vitro inhibition of rat arterial smooth muscle cell growth by extractive sulfated mucopolysaccharides

The effect of a sulfated mucopolysaccharide mixture of known composition, extracted from pig duodenum, was studied on the proliferation of rat arterial smooth muscle cells cultured from rat aorta. Cell growth, stimulated by fetal calf serum, was monitored by direct cell count and by determination of the mitotic index. The extractive mixture was studied in comparison with commercial heparin, with heparin with different electrophoretic mobilities in barium acetate and with dermatan and heparan sulfates. Heparins and the extractive mucopolysaccharide mixture inhibited cell growth measured at various time intervals, and in their presence the proliferation of smooth muscle cells plateaued at lower cell densities. Dermatan and heparan sulfates were either inactive or significantly less effective than the other mucopolysaccharides. A short preincubation (3 h) of smooth muscle cells with the extractive mixture, followed by incubation with the growing medium with no mucopolysaccharides added, slowed the cell growing rate, suggesting an interaction of the mixture components with the cell surface.