Artery最新文献

The peptide FS2 is a mamba venom toxin, consisting of 60 amino acids, three residues of which are different from those of calciseptine (CaS), a natural L-type Ca2+ channel blocker. The biological activities of synthetic FS2 for L-type Ca2+ channels were determined under comparisons to those of CaS and nitrendipine, a 1,4-dihydropyridine derivative. Similar to CaS, FS2 competitively inhibited the binding of [3H]nitrendipine to rat brain synaptosomal membranes on Lineweaver-Bulk plot, with Kd value of 210 nM, which was similar to that of CaS being 290 nM, but did not affect binding of an N-type Ca2+ channel ligand omega-[125I]-conotoxin GVIA to the membranes. Pretreatment of A7r5 cells with either FS2 or CaS at concentrations of 10(-8) M and greater for 5 min significantly and dose-dependently reduced 10(-6) M Bay K8644-induced increase in the cytosolic free Ca2+ concentration ([Ca2+]i) of the cells determined by the fluorescent Ca2+ indicator fura-2, with the half inhibitory concentrations (IC50) of 2.3 x 10(-8) and 2.7 x 10(-8) M, being similar to that of the IC50 value of nitrendipine (4.4 x 10(-8) M). These observations indicate that FS2, similar to CaS, is an active natural L-type Ca2+ blocker sharing the binding site on the channels with the 1,4-dihydropyridines.

Intimal plus media thickening has been described to be associated with several cardiovascular risk factors. Aim of the present study was to evaluate the intimal plus media thickness in male subjects with hypertension compared to age matched males normotensive controls. Twenty subjects with hypertension, defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg and/or use of antihypertensive drugs, and forty age matched controls have been enrolled. Intimal plus media thickness has been measured from B-mode echography images by a computer. Plasma lipids have been measured by routine methods. A zero random sphygmomanometer has been used to detect blood pressure. Intima plus media thickness resulted enlarged in subjects with hypertension compared to normotensive controls. The thickening of intima-media complex seems related to atherosclerotic lesions, therefore its early detection by noninvasive techniques might improve the identification and the monitoring of high risk hypertensive subjects.

The effects of 26-hydroxycholesterol on 45Ca++ uptake, [14C]cholesterol uptake, [14C] acetate incorporation and the concentrations of 26-hydroxycholesterol and cholesterol in the plasma membrane were studied in cultured human smooth muscle cells isolated from umbilical arteries. The results showed that: (1) 26-hydroxycholesterol enhanced markedly 45Ca++ uptake and the enhancement was not diminished by nifedipine; (2) 26-hydroxycholesterol decreased cholesterol content in plasma membrane by inhibiting cholesterol uptake and synthesis, and [14C]cholesterol uptake was not LDL-receptor dependent; (3) 26-hydroxycholesterol induced a shift of [14C] acetate from cholesterol into phospholipid synthesis, but the radioactive incorporation into triglyceride and cholesterol ester was inhibited by 26-hydroxycholesterol; and (4) 26-hydroxycholesterol inserted itself into the plasma membrane. We suggested that 26-hydroxycholesterol changes the composition of membrane lipids with a consequential alteration of membrane permeability to Ca++.

The present study was designed to investigate on possible association between SstI polymorphism in the ApoAI-CIII-AIV gene cluster, classical coronary heart disease risk factors and extracoronary atherosclerosis. One hundred and twenty six male subjects were enrolled and underwent echo-Doppler examination of carotid and femoral arteries, coronary heart disease risk factors assessment and SstI genotyping. The frequency of the rare SsI allele was 12.1% and 6.7% in subjects with or without extracoronary lesions respectively and was not associated with differences in the distribution of coronary heart disease risk factors. Forty subjects had hypertension, 34 homozygous for the frequent allele and 6 with presence of the rare allele. Among these, 10 subjects (29%) and 5 subjects (83%), respectively, had extracoronary atherosclerosis. Furthermore, subjects homozygous for the rare allele exhibited lipid abnormalities and a family history positive for hypertension and/or hyperlipidemia. These findings suggest a possible role for the ApoAI-CIII-AIV gene complex in both lipid metabolism and blood pressure regulation and could be of help to identify, within hypertensives, those subjects prone to extracoronary atherosclerosis.

The effect of amiprilose hydrochloride, a synthetic monosaccharide, on smooth muscle cell proliferation was studied in vitro. Using porcine aortic smooth muscle cell cultures, amiprilose significantly inhibited cell proliferation in a dose-dependent fashion at concentrations of 0.5-1.0 mg/ml. This antiproliferative effect was reversible upon removing amiprilose by cell washing and adding fresh media. Pretreating cells with amiprilose before serum stimulation did not affect subsequent growth. Inhibition of proliferation occurred when amiprilose was added up to 48 hours after serum stimulation. As such, amiprilose deserves further investigation as a potential therapeutic agent in preventing restenosis after angioplasty.

Protein synthesis was measured in incubated aortic smooth muscle and fast-twitch extensor digitorum longus (EDL) in both sham operated and adrenalectomized (ADX) rats. The studies were performed on four groups: a) untreated controls; b) rats treated with tumor necrosis factor (TNF) @ 50 micrograms/kg. b.w.; c) rats treated with cortisone @ 100 mg/kg/day for 5 days; or d) rats treated with cortisone plus TNF. Both TNF and cortisone suppressed protein synthesis in the aortic smooth muscle and EDL in intact animals. TNF given together with cortisone, induced a significant additional decrease in protein synthesis in both muscle types as compared to cortisone-treated rats. The rate of protein synthesis in aortic smooth muscle from sham operated rats was control > TNF > cortisone > Cortisone+TNF; in the case of EDL, rate was control > cortisone > TNF > Cortisone+TNF. In ADX animals, TNF alone did not affect protein synthesis in both aortic smooth muscle and EDL. Though cortisone alone produced a significant inhibition of protein synthesis, there was no significant further decline in protein synthesis when cortisone was given together with TNF. These findings suggest that the inhibitory effect of TNF on muscle protein synthesis is mediated through glucocorticoids.

Patients (40 cases) were treated with daily dosage of warfarin of 2-7 mg after being undergone artificial valve replacements. Twenty one days after administration of warfarin, we examined the patients for kinetics of K vitamins and vitamin K-dependent coagulation factors in blood, and intestinal flora in feces, as well as the relationship between K vitamins and coagulation activity. The following results were obtained. (1) In warfarin-administered patients (Group B), blood levels of vitamin K1 and menaquinone-7, a vitamin K2 homologue, were similar to those in non-warfarin-administered patients. Therefore, administration of warfarin did not significantly decreased the levels. (2) In patients selected randomly from Group B (Group C), the vitamin K1 level in feces was higher than that in non-warfarin-administered patients. The menaquinone-7 level in feces was similar to that in non-warfarin-administered patients. For the total counts of bacteria and the detection rate of vitamin K2-producing bacteria, there was no significant difference between Group C and non-warfarin-administered patients. (3) The above mentioned results of (1) and (2) suggest that it is important for development of anticoagulant effects by warfarin to inhibit conversion from vitamin K1 to reduced vitamin K1, as well as to inhibit the reducing process from vitamin K1-epoxide to vitamin K1. (4) Vitamin K1-epoxide, a metabolite of vitamin K1, appeared in blood after administration of warfarin; there was a lower correlation between the blood level of vitamin K1-epoxide and the warfarin dosage. Further, PIVKA-II appeared in blood after administration of warfarin; there was a inverse lower correlation between the level of PIVKA-II and HPT, and between PIVIKA-II and TT. In conclusion, it has been clarified that vitamin K1-epoxide and PIVKA-II are useful parameters to evaluate anticoagulant effect of warfarin.

We examined the formation of F-actin filaments and the expression of beta 1 integrin in human vascular endothelial cells cultured on type V collagen. The cells attached to the exogenous substrate, formed complete F-actin filaments, and expressed vinculin and beta 1 integrin 0.5-1 h after inoculation. These phenomena are referred to as the first ECM-integrin-cytoskeleton system. After 3-6 h, disassembly of the F-actin filaments was observed to occur from the leading edges, and the cells developed focal adhesions only in their central regions. After 12-24 h, the cells on the type V collagen failed to form the second ECM-integrin-cytoskeleton system, and gradually detached from the substrate. In contrast, the cells on type I collagen developed both the first and second system, and acclimatized themselves to the environment. Thrombospondin (TSP), an anti-adhesive protein, was capable of inhibiting the spreading of the cells both after 1 h and 24 h. However, type V collagen treated with TSP inhibited the cell spreading after 1 h, but not after 24 h. The attachment and spreading of the cells on type V collagen were little affected by an anti-TSP antibody and the synthetic peptide GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro), which significantly inhibited the attachment and spreading of the cells on TSP. Taken together, these results suggest that the cell detachment from type V collagen is not attributed to endogenously produced TSP (or member of TSP family) with anti-adhesive properties, but resulted from the failure to reconstitute the second ECM-integrin-cytoskeleton system in focal adhesion.

The effect of pravastatin, an inhibitor of HMG-CoA reductase, on the metabolism of human low density lipoprotein (LDL) was examined in guinea pigs. Pravastatin treatment significantly reduced plasma levels of total cholesterol and LDL-cholesterol by 15.6 mg/dl (38.8%) and 12.7 mg/dl (42.9%), respectively. We investigated the metabolism of LDL in pravastatin-treated and untreated guinea pigs using the simultaneous intravenous injection of 131I-labeled LDL and 125I-labeled, galactose-treated LDL to quantify the LDL receptor pathway. Pravastatin increased the fractional catabolic rate (FCR) of the LDL receptor-dependent pathway. The treatment with pravastatin did not alter the FCR of the LDL receptor-independent pathway. The FCR of the LDL receptor-dependent pathway was higher for LDL isolated from pravastatin-treated subjects than for LDL isolated from control subjects. These findings suggest that pravastatin mainly reduced plasma cholesterol levels by accelerated FCR of the LDL receptor-mediated pathway.

A recent review article on the pathogenesis of atherosclerosis stated that the lesions result from an excessive inflammatory-fibroproliferative response to various forms of insult of the endothelium and smooth muscle cells of the arterial wall, that a large number of growth factors participate in this process and that the injury is most apparent at branching points of the arterial tree. We found a significant increase in sphingomyelin and a decrease in other phospholipid components in the arterial wall at the branching points as compared to the non branching points of human and swine arteries. Because of the higher transition temperature of sphingomyelin, its replacement of other phospholipid components may increase the rigidity of the cell membrane and may alter negatively charged bilayers in such a way that they interact more strongly with cholesterol and calcium. Duplication of such conditions with arterial cells in tissue culture caused calcium infiltration into the cell. Furthermore, platelet derived growth factor (PDGF) synthesis was increased in smooth muscle cells grown in magnesium deficient media. It is possible that a change in phospholipid and cholesterol composition of arterial cells at the branching points of arteries and that factors other than PDGF may precede inflammatory-fibroproliferative response to various forms of insult.