Arteriosclerosis In Rats Research Articles

Curcumol reduces lower limb arteriosclerosis in rats by inhibiting human arterial smooth muscle cell activity.

Cardiovascular diseases, particularly those involving arterial stenosis and smooth muscle cell proliferation, pose significant health risks. This study aimed to investigate the therapeutic potential of curcumol in inhibiting platelet-derived growth factor-BB (PDGF-BB)-induced human aortic smooth muscle cell (HASMC) proliferation, migration and autophagy. Using cell viability assays, 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays and Western Blot analyses, we observed that curcumol effectively attenuated PDGF-BB-induced HASMC proliferation and migration in a concentration-dependent manner. Furthermore, curcumol mitigated PDGF-BB-induced autophagy, as evidenced by the downregulation of LC3-II/LC3-I ratio and upregulation of P62. In vivo experiments using an arteriosclerosis obliterans model demonstrated that curcumol treatment significantly ameliorated arterial morphology and reduced stenosis. Additionally, curcumol inhibited the activity of the KLF5/COX2 axis, a key pathway in vascular diseases. These findings suggest that curcumol has the potential to serve as a multi-target therapeutic agent for vascular diseases.

HK-1000 약침이 흰쥐의 고지혈증 및 동맥경화증에 미치는 영향

Objective&Methods: The purpose of this study is to observe the effects of HK-1000 Herbal-acupuncture solution at GB34(Yangleungchean) on hyperlipidemia and arteriosclerosis in rats. The author performed several experimental items to analyze the levels of various components and enzymes in serum, urine and liver, as well as the histological change of liver and aorta. Results: 1. HK-1000 herbal-acupuncture infusion increased the cell viability rate, DPPH radical scavenging activity and HMG-CoA reductase inhibition rate in rat liver cells. 2. The levels of total cholesterol, free cholesterol, LDL-cholesterol, phospholipid in serum and AI(atherogenic index) were decreased, and the ratio of HDL to TCL(HDL/TCL) and the level of TG in serum were increased as compared with those of the control group. 3. In the HK-1000 group, serum AST and ALT were significantly lower than those of the HG group and saline group. 4. Hepatic GSH and catalase activities were significantly increased as compared with those of the saline group. Conclusions: From the above results, it is suggested that HK-1000 herbal-acupuncture at GB34 has a therapeutic effect on hyperlipidemia and arteriosclerosis.

HMG-CoA reductase inhibition improves anti-aging klotho protein expression and arteriosclerosis in rats with chronic inhibition of nitric oxide synthesis

Background The klotho gene and its protein product are mainly expressed in the kidney. The klotho protein induces suppression of multiple aging-related phenotypes, and homozygous klotho gene mutant mice display various senescent morbidity. Chronic inhibition of nitric oxide synthase (NOS) induces arteriosclerosis, while HMG-CoA reductase inhibitors (statins) have pleiotropic vascular protective effects besides cholesterol lowering. Therefore, the present studies were performed to determine whether chronic NOS blockade would affect anti-ageing klotho protein expression. In addition, the effects of statins on klotho protein expression and arteriosclerosis in these rats were investigated. Methods Forty-two rats were divided into 6 groups as follows: (1) control, (2) NOS blockade, (3) atorvastatin (10 mg/kg/day), (4) pitavastatin (3 mg/kg/day), (5) NOS blockade + atorvastatin, (6) NOS blockade + pitavastatin. To induce arteriosclerosis further, a cuff was placed around the left femoral artery in each rat. After 4 weeks observation, rats were killed and renal klotho expression and the level of arteriosclerosis were examined. Results The rats of chronic NOS inhibition developed hypertension, while statin treatment did not affect blood pressure in the rats with or without NOS blockade. Despite statin treatment, plasma levels of lipids did not differ among 6 groups. Immunohistochemical staining revealed that klotho protein was localized in the renal tubules. Chronic NOS inhibition markedly reduced renal klotho protein expression, while treatment with atorvastatin or pitavastatin completely prevented the reduction of klotho expression induced by NOS inhibition. In addition, statin treatment significantly improved arteriosclerotic lesions induced by NOS inhibition and cuff placement. Conclusion Since statin treatment did not alter blood pressure or serum lipid profiles, a novel vascular protective effect of statins via enhancing anti-aging klotho protein expression is suggested.

Reciprocal Expression of Vascular Endothelial Growth Factor and Nitric Oxide Synthase by Coronary Arterial Wall Cells during Chronic Inhibition of Nitric Oxide Synthesis in Rats

Chronic inhibition of nitric oxide (NO) synthesis by oral administration of N^G-nitro-L-arginine methyl ester (L-NAME) causes hypertension and produces arteriosclerosis in rats. Balloon injury induces upregulation of vascular endothelial growth factor (VEGF) in medial smooth muscle cells of the rat arterial wall, and NO secreted by a restored endothelium acts as the negative feedback mechanism that downregulates VEGF expression to basal levels. In this study, we tested the hypothesis that a reciprocal relation between VEGF and NO would be established in a rat model of chronic NO blockade. Male Wister rats received plain drinking water (n = 10) or L-NAME (0.5 mg/ml) in the drinking water (n = 11) for 6 weeks. After 6 weeks, the wall-to-lumen ratios and perivascular fibrosis in the coronary arteries were greater in the L-NAME group than in the control group. NO synthase-positive cells in the intima were abundantly observed in the control group, whereas no such cells were seen in the L-NAME group. In contrast, the number of VEGF-positive smooth muscle cells in the media was greater in the L-NAME group than in the control group. These findings strongly suggest a reciprocal relation between VEGF and NO even in a rat model of chronic NO blockade.

Regression by ACE inhibition of arteriosclerotic changes induced by chronic blockade of NO synthesis in rats

We previously reported that chronic inhibition of nitric oxide (NO) synthesis with N(omega)-nitro-L-arginine methyl ester (L-NAME) induces vascular inflammation at week 1 and produces subsequent arteriosclerosis at week 4 and that cotreatment with an angiotensin-converting enzyme (ACE) inhibitor prevents such changes. In the present study, we tested the hypothesis that treatment with an ACE inhibitor after development of vascular inflammation could inhibit arteriosclerosis in rats. Wistar-Kyoto rats were randomized to four groups: the control group received no drugs, the 4wL-NAME group received L-NAME (100 mg x kg(-1) x day(-1)) for 4 wk, the 1wL + 3wNT group received L-NAME for 1 wk and no treatment for the subsequent 3 wk, and the 1wL + 3wACEI group received L-NAME for 1 wk and the ACE inhibitor imidapril (20 mg x kg(-1) x day(-1)) for the subsequent 3 wk. After 4 wk, we observed significant arteriosclerosis of the coronary artery (medial thickening and fibrosis) and increased cardiac ACE activity in the 1wL + 3wNT group as well as in the 4wL-NAME group, but not in the 1wL + 3wACEI group. In a separate study, we examined apoptosis formation and found that posttreatment with imidapril (20 mg x kg(-1) x day(-1)) or an ANG II AT1-receptor antagonist, CS-866 (5 mg x kg(-1) x day(-1)), induced apoptosis (TdT-mediated nick end-labeling) in monocytes and myofibroblasts appearing in the inflammatory lesions associated with a clear degradation in the heart (DNA electrophoresis). In conclusion, treatment with the ACE inhibitor after 1 wk of L-NAME administration inhibited arteriosclerosis by inducing apoptosis in the cells with inflammatory lesions in this study, suggesting that increased ANG II activity inhibited apoptosis of the cells with inflammatory lesions and thus contributed to the development of arteriosclerosis.

Beneficial effect of proteases on allograft arteriosclerosis in a rat aortic model

Recently it has been shown that protease therapy ameliorates certain immune-mediated diseases. Thus we studied the effect of administration of a protease mixture on aortic transplant arteriosclerosis in rats. Segments of abdominal aorta from SHR strain were transplanted orthotopically into WKY recipients. Two groups of allografted rats were used. One group (n = 8) was treated with daily intraperitoneal injections of 12 mg of a protease formulation containing trypsin, bromelain and rutosid, and another group (n = 8) with placebo. Eight WKY rats were transplanted with syngenic aortas and treated with placebo. After 8 weeks, structural changes of the grafted segment were evaluated by morphometric analysis of formalin-fixed sections with specific stains. In untreated allografts there was a marked intimal thickening, medial necrosis with disruption of elastic fibres, and inflammatory infiltrates in the adventitia. Administration of proteases inhibited formation of neointima by 59.0% when cross-sectional areas were compared (80+/-11 versus 195+/-11 microm2, P<0.01; protease-versus placebo-treated allograft recipients respectively) and decreased medial injury as estimated by the integrity of elastic fibres and smooth-muscle cell density. Thus, in an experimental model of rat aortic allograft, protease administration ameliorates rejection-induced arterial wall remodelling.

Hyperlipidemia accelerates allograft arteriosclerosis (chronic rejection) in the rat.

The relevance of hyperlipidemia in allograft arteriosclerosis (chronic rejection) is controversial. Isolated hypercholesterolemia induced with cholesterol-cholic acid-diet (CC-diet) or hypertriglyceridemia induced with glycerol-diet (G-diet) had no or only a protective effect on aortic allograft arteriosclerosis in the rat. Combined hyperlipidemia with both diets (CC+G-diet) enhanced allograft arteriosclerosis by doubling intimal thickness and cellularity (P < .05) but had no effect on host arteries. Compared with normolipidemic controls, the CC+G-diet increased the total serum cholesterol concentration 4.8-fold (P < .05). Levels of VLDL2 and IDL increased 4.8- and 18.1-fold (P < .05), and their composition changed from triglyceride-rich to cholesterol-rich lipoproteins in an atherogenic direction. The CC+G-diet had no effect on the structure of inflammation in the vascular wall. Instead, significant lipid deposits were observed, and the expression of epidermal growth factor and insulin-like growth factor-1 was significantly elevated in the vascular wall. Thus, elevations in VLDL and IDL lipoprotein levels and their cholesterol content associate with the generation of allograft arteriosclerosis in rats. Deposition of lipids in the vascular wall seems to induce local synthesis of certain growth factors, which ultimately leads to the induction of smooth muscle cell replication.

Elastaseと動脈硬化に関する研究

Since Baló and Banga found that elastase had an action of degrading elastin, many reports on the relationships between arteriosclerosis and elastase were published. Hall found that elastase had two component, one is elastoproteinase, which shows protein digesting activity, and the other, elastomucase which has lipolytic activity.Previous study showed that elastase had an antiarterisoclerotic action in rat induced fed with atherogenic diet and vitamin D2 for four days orally. The mechanism of antiarteriosclerotic action of elastase were assumed to be a regulating action of biosynthesis of elastin in the arterial wall.In this paper, the results on regression of arteriosclerosis in rats were presented.Fourty arteriosclerotic rats experimentally induced fed with atherogenic diet together with 4 days vitamin D2 at weeks 7 were divided into 4 groups; (1) Group R-N fed with standard diet. (2) Group R-NE fed with standard diet and treated with elastase (I. M. 450 El.U/kg/day). (3) Group R-A fed with atherogenic diet continuously. (4) Group R-AE fed with atherogenic diet and treated with elastase continuously.At 12 and 15 weeks during the experiment, the changes in aortic elastic fibers were determined in these four groups of rats. There were little changes between Group R-N and R-NE at week 12, but when compared with the Group R-N and R-NE at week 15 respectively, the latter group showed less fissure of elastic fibers. In sharp contrast to the Group R-A, Group R-AE revealed much less marked interstitial rarefaction and fissure of elastic fibers at 12 as well as 15 weeks, which suggests that elastase and standard diet could bring about an action of regressing experimental arteriosclerosis of rats induced fed with atherogenic diet and 4 days vitamin D2.

The effect of clofibrate on spontaneous arteriosclerosis in rats

Multiparous rats develop a spontaneous arteriosclerosis. The effect of clofibrate on the incidence and severity of the disease was studied in breeding female rats each of which had had 6 litters. Clofibrate was administered in the diet at a level of 0.25%. Groups of treated rats were killed after 3, 6 and 12 months' treatment with a similar number of controls at each time. The aortas were dissected out from heart to diaphragm, radiographed and examined histologically. The kidneys, adrenals, heart, liver, and ovaries of each animal were also examined histologically. The results of the experiments demonstrated that clofibrate decreases the severity and incidence of the disease. Its chief effect appears to be to reduce the calcification and mucopolysaccharide content of the aorta. There is no correlation between arteriosclerosis and kidney disease but clofibrate also reduces the incidence of nephropathy. Histological changes in the adrenal glands were less severe in the clofibrate treated rats.