A Case-control Study on the Risk Factors for Ischemic Colitis.

OBJECTIVE: Ischemic colitis (IC) is a relatively common acute inflammation disorder of the intestine. It was considered to be a disorder of elderly people with risk factors for arteriosclerosis; however, a considerable number of young people with IC have been reported recently. We performed a case-control study to determine the risk factors for IC and compare the risk factors between elderly and non-elderly people. METHODS: The study included 209 consecutive patients diagnosed with IC between December 2004 and March 2017 at Tokai University Hospital. The study also included 209 randomly selected controls in the same calendar year so as to match age and sex. Possible risk factors for IC were identified and compared between age groups. RESULTS: The mean age of IC group was 64.9 with 60 males and 115 elderly patients aged 65 or more in each group. On multivariable conditional logistic regression analysis, drinking, abdominal surgery, hypertension, and malignant diseases were risk factors for IC in all ages. In non-elderly patients, only hypertension and laxative/enema use were significant factors, while in elderly, abdominal surgery, hypertension, COPD, malignant disease and antiplatelet drugs were significant. CONCLUSION: The risk factors in elderly people might be quite different from younger ones, while hypertension seemed to be a common risk in all ages.

[Vascular Calcification - Pathological Mechanism and Clinical Application - . Vascular calcification in chronic kidney disease-mineral and bone disorder (CKD-MBD)].

Chronic kidney disease-mineral and bone disorder (CKD-MBD), is sequential pathophysiology that starts in the very early stages of CKD. Three major aspects of CKD-MBD are laboratory abnormalities, bone abnormalities and vascular calcification. In dialysis patients, the prevalence of death due to cardiovascular disease accounts for more than 40% of all-cause mortality. Therefore, arteriosclerosis with vascular calcification may be an important pathophysiological mechanism in the development of cardiovascular disease. Vascular calcification is known to be an important risk factor influencing mortality in CKD patients. A number of studies have suggested a close association between serum FGF23 concentration and the risks of mortality, cardiovascular disease vascular calcification as well as CKD progression. Renal insufficiency leads to decline in klotho level and impaired phosphate excretion. However serum phosphate levels are maintained in the normal range by up regulation of FGF23 and PTH in early CKD stage. Early treatment intervention is necessary to improve the prognosis of the CKD patient.

Antioxidant and anti-atherogenic activities of three Piper species on atherogenic diet fed hamsters.

Atherogenic diet is known to induce high plasma lipid concentration, oxidative stress and early atherosclerosis. Antioxidants have potentials to counter the effect of atherogenic diet. The present research aims at evaluating the antioxidant and anti-atherosclerotic activities of three Piper species (Piper guineense, Piper nigrum and Piper umbellatum) on atherogenic diet fed hamsters. Hamsters divided into 8 groups: normal control, atherosclerotic control and six test groups. The normal animals fed normal rodent chow, the atherosclerotic control animals fed the same rodent chow supplemented with 0.2% cholesterol and 10% coconut oil (high cholesterol diet). The 6 test groups' animals fed same diet as the atherosclerotic control group but with additional supplementation of 2 graded doses (1 and 0.25 mg/kg body weight, o.p.) of plant extracts for 12 weeks. The atherogenic diet induced a collapse of the erythrocyte antioxidant defense system (significant decrease in superoxide dismutase, catalase and glutathione peroxidase activities). Atherogenic diet also induced an increase in plasma total cholesterol, triglyceride, thiobarbituric acid reactive substances (TBARS), oxidation of low density lipoprotein cholesterol (LDL) and accumulation of foam cells in the aorta a hall mark for atherosclerosis. Administration of the Piper species prevented the collapse of the antioxidant system and the increase of plasma parameters maintaining them towards normality. The Piper species also prevented LDL oxidation by increasing the time (lag time) for its oxidation. The results suggest that these Piper species have significant antioxidant and anti-atherogenic effect against atherogenic diet intoxication.

Omega-3 fatty acids do not improve endothelial function in virologically suppressed HIV-infected men: a randomized placebo-controlled trial.

Omega-3 fatty acids decrease cardiovascular disease (CVD) mortality possibly due to antiinflammatory effect. Inflammation and endothelial dysfunction likely play a role in the heightened CVD risk in HIV. Our goal was to evaluate the effect of omega-3 fatty acids primarily on endothelial function and inflammation in HIV-infected adults with moderate CVD risk on stable antiretroviral therapy. We conducted a 24-week, randomized, double-blind, placebo-controlled study to evaluate the effect of omega-3-acid ethyl esters 1 g twice a day. Flow-mediated dilation (FMD) of the brachial artery, lipoproteins and markers of inflammation, endothelial activation, coagulation, and insulin resistance were measured at entry and week 24. There were no within- or between-group differences in change in FMD over 24 weeks (mean change in FMD -0.13% vs. 1.5% for treatment vs. placebo; p=0.21). There were no between-group differences in changes in lipoprotein levels or biomarkers tested, except soluble tumor necrosis factor receptor-I, which favored omega-3-acid ethyl esters. Omega-3 fatty acids did not improve endothelial function or activation, coagulation, or insulin resistance in virologically suppressed, HIV-infected men with moderate CVD risk; however, inflammation tended to improve. This suggests that omega-3 fatty acids may not be potent enough to counteract the enhanced inflammation and endothelial dysfunction due to HIV and antiretrovirals.

[Effect of tongmal recipe on atherosclerosis in patients with early lower extremity arteriopathy caused by type 2 diabetes mellitus].

OBJECTIVE: To observe the effect of Tongmai Recipe (TMR) on atherosclerosis (AS) in patients with early lower extremity arteriopathy disease (LEAD) caused by type 2 diabetes mellitus (T2DM). METHODS: Patients were randomly assigned to two groups. The 23 patients in the treatment group were treated by TMR and the 22 in the control group were given Cilostazo, all for 3 months. Before and after treatment, lower extremity vascular color Doppler image, blood levels of glucose, insulin, serum matrix metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6) were measured. RESULTS: The thickness of AS plaque and that of arterial intima-media obviously reduced (P < 0.01 and P < 0.05), insulin sensitivity improved noticeably (P < 0.01), and serum levels of MMP-9 and IL-6 lowered obviously (P < 0.05) in the treatment group after treatment, but these indexes were unchanged in the control group statistically. CONCLUSION: TMR has remarkable action in reducing the thickness of AS plaque and intima-media of artery, its mechanism might be related with improving of insulin sensitivity and anti-inflammatory reaction, and reducing of serum MMP-9 level as well in patients.

The inhibitory effect of astilbin on the arteriosclerosis of murine thoracic aorta transplant.

The inhibitory effect of astilbin on transplant arteriosclerosis in murine model of thoracic aorta transplantation was examined. Model of rat thoracic aorta transplantation was established. Ninety rats were divided into three groups. In isograft group, the thoracic aorta of Brown Norway (BN) rat was anastomosed with the abdominal aorta of another BN rat. In allograft group, the thoracic aorta of BN rat was anastomosed with the abdominal aorta of Lewis rat. In astilbin group, the rats receiving allo-transplantation were given astilbin 5 mg/kg per day for a time of 28 days. The donor thoracic aorta and the recipient abdominal aorta were anastomosed by means of a polyethylene cannula (inner diameter: 1.5 mm, length: 3 mm length). The grafts were histologically examined for structural changes. The areas of arterial lumen and endatrium were calculated. Our results showed that, in the allograft group, 28 days after allografting, conspicuous proliferation of smooth muscles and infiltration with a great number of inflammatory cells were found in the tunica intima and tunica media. Astilbin significantly inhibited the proliferation of smooth muscles and ameliorated the infiltration of inflammatory cells thereby prevent against the development of transplant arteriosclerosis. It is concluded that asltilbin can effectively prevent the development of arteriosclerosis in allotransplant by inhibiting the proliferation of smooth muscles and inhibit the proliferation of smooth muscles in tunica of intima and media and reducing infiltration of the inflammatory cells.

[Arteriosclerosis and vascular calcification in chronic kidney disease (CKD) patients].

Chronic kidney disease (CKD) patients are belonging to high risk patients to atherosclerosis with vascular calcification. These patients are well recognized advanced arteriosclerosis with vascular medial calcification, with high risk of cardiovascular death. With basic investigated results, the mechanism of vascular calcification is making clear. A lot of various factors which participate in calcification have been specified. Especially, in long term dialysis patients, the very high grade vascular calcification with advanced atherosclerosis is common with calcium/phosphate/PTH and skeletal problem. This CKD related metabolic bone disorder (CKD-MBD) highly induced and progressed vascular calcification. Participates in vascular calcification. It is extremely important in order to prevent vascular calcification to manage serum phosphorus, serum calcium and parathyroid function within the suitable range. In addition, hyperphosphatemia is becoming the powerful risk factor for patients' survival. The new powerful phosphate binder is developing. The beneficial effect of the new agent on patients' survival is now focused.

Drug therapy of high-risk lipid abnormalities in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, with the Council on Cardiovascular Nursing.

Despite compliance with lifestyle recommendations, some children and adolescents with high-risk hyperlipidemia will require lipid-lowering drug therapy, particularly those with familial hypercholesterolemia. The purpose of this statement is to examine new evidence on the association of lipid abnormalities with early atherosclerosis, discuss challenges with previous guidelines, and highlight results of clinical trials with statin therapy in children and adolescents with familial hypercholesterolemia or severe hypercholesterolemia. Recommendations are provided to guide decision-making with regard to patient selection, initiation, monitoring, and maintenance of drug therapy.

Physical training and metabolic supplementation reduce spontaneous atherosclerotic plaque rupture and prolong survival in hypercholesterolemic mice.

Moderate physical exercise (PE) combined with metabolic treatment (MT) (antioxidants and l-arginine) are well known to reduce atherosclerotic lesion formation in hypercholesterolemic mice. However, the long-term beneficial effects on unstable atheroma remain poorly understood. We started early PE training in large groups of 6-week-old hypercholesterolemic mice (by graduated swimming) alone or in combination with nutritional supplementation (1.0% vitamin E added to the chow and 0.05% vitamin C and 6% l-arginine added to the drinking water). Inactive controls did not receive PE. The spontaneous development of atherosclerotic plaque rupture (associated with advanced atherosclerosis) and survival rates were evaluated. Moderate PE elicited an increase in plasma levels of nitric oxide. Early combined treatment with PE and MT in the hypercholesterolemic mice significantly reduced lesions (also detected noninvasively at 10 months) and spontaneous atherosclerotic plaque rupture and prolonged survival more effectively than each intervention alone. Thus, early concerted actions of MT and PE improve the natural history of atherosclerotic lesions and reduce the plaque instability in hypercholesterolemic mice.

Effects of dietary calcium on atherosclerosis, aortic calcification, and icterus in rabbits fed a supplemental cholesterol diet.

BACKGROUND: Vascular calcification is implicated in myocardial infarction, instability and rigidity of the aortic wall, and bioprosthetic failures. Although an increase in the calcium (Ca) content in atherogenic diets has been shown to decrease atherosclerosis in rabbits, whether Ca supplementation and deficiency can affect atherosclerosis-related aortic calcification remains unknown. RESULTS: New Zealand White male rabbit littermates were fed an atherogenic diet containing 0.5% cholesterol and 2% peanut oil. The Ca content of the diet, which normally contains 1%, was adjusted to 0.5 or 3%. Segments of thoracic aortas were dissected from rabbits for histological evaluations and Ca and Pi determinations. Rabbits with calcium supplementation were maintained for 4 months, whereas those with calcium deficiency were maintained for 2 1/2 months due to severe icterus beyond this stage. The ratios of intimal to medial areas and calcified to intimal areas were used to semi-quantify lesion accumulation and calcification, respectively. Icterus was estimated from the extent of yellowing of the skin, sclera, and mucous membranes along with gross evidence of hepatic lipidosis and/or biliary obstructions. Statistical analysis of 16 matched littermates shows that Ca supplementation significantly decreased the lesions by 41% (p < 0.05) and markedly inhibited calcification by 62% (p < 0.05). Statistical analysis of 11 matched littermates shows that Ca deficiency significantly increased the lesions by 2.7-fold (p < 0.05) and that the diet caused a small but significant calcification not seen in the sibling groups with normal dietary Ca. Ca supplementation caused a significant 30% decrease in serum cholesterol (p < 0.05). Calcium deficiency increased serum cholesterol by 57% (p < 0.001). Serum cholesterol and LDL-cholesterol levels in Ca deficient rabbits were 2-fold higher than those with high Ca diets. Ca supplementation decreased soluble Ca and Pi content in aortas, suggesting that this effect may underlie the effects of Ca supplementation on calcification. Calcium deficiency increased icterus by 33% (p < 0.05), which may affect hepatic clearance of cholesterol, while calcium supplementation decreased it by 43% (p < 0.001). CONCLUSION: Ca supplementation to an atherogenic diet inhibits atherosclerosis, aortic calcification, and icterus, whereas a Ca deficient-diet promotes them.

Plasma lipid peroxidation and antioxidiant nutrients in type 2 diabetic patients.

BACKGROUND AND OBJECTIVE: Observation shows diabetic patients to be more prone to oxidative stress because of hyperglycemia. The elevation of free radical production by this hyperglycemic production may exacerbate cardiovascular complication in diabetes. This study aims to investigate the oxidative stress related parameters in type 2 DM. Since the effects of glycemic control and cardiovascular complications in DM on these parameters has been not fully determined, the comparison between plasma MDA (malondialdehyde) and antioxidant nutrients with their age-matched normal healthy group may be used to determine the susceptibility of oxidative stress in this type of DM. MATERIAL AND METHOD: MDA and antioxidant nutrients (vitamin A, C, E and beta-carotene) were analyzed in plasma of 19 subjects with poorly controlled type 2 DM (fasting plasma glucose [FPG] > 180 mg/dl), 26 subjects with fairly controlled type 2 DM (FPG < or = 180 mg/dl), and 20 subjects with type 2 DM complicated coronary heart disease (CHD) who were matched for age and gender. Twenty healthy subjects with normal plasma glucose level (FPG < 110 mg/dl) and matched for age and gender served as a control group. In all groups of DM these oxidative stress parameters were compared to a normal group. RESULTS: The plasma MDA levels were significantly higher in all types of DM compared to age-matched normal control. Plasma antioxidant vitamin C and E significantly lower only in poorly controlled and CHD complicated type 2 DM, respectively. The mean of plasma vitamin E level was lowest in type 2 DM complicated with CHD. No significant differences in both plasma vitamin A and beta-carotene were noted between any types of DM and age-matched normal healthy group. The positive correlation between MDA and FPG was demonstrated in most group of patients with their normal subjects except in fairly controlled type 2 DM and negative correlation between vitamin E and FPG was also demonstrated in type 2 DM with CHD. CONCLUSION: These findings suggested that diabetic patients were susceptible to oxidative stress and higher plasma glucose level had an association with free radical-mediated lipid peroxidation. The lowest level of vitamin E in type 2 DM complicated with CHD indicated that oxidative stress played an important role in cardiovascular complication and vitamin E supplementation may be necessary for treatment and prevention in this group of diabetics.

Antiatherogenic effects of structured lipid containing conjugated linoleic acid in C57BL/6J mice.

Conjugated linoleic acids (CLA) were enzymatically acidolyzed with olive oil to produce structured lipids (SL), and their antiatherosclerotic properties were investigated in C57BL/6J mice. Twenty-eight mice were divided into four groups and fed control diet or atherogenic diets supplemented with high cholesterol and high fat (HCHF) containing 5% of lard, olive oil, or SL based on control diet for 4 weeks. The supplementation of SL diet (0.6% CLA) significantly reduced the levels of serum total cholesterol and total triglyceride and increased high-density lipoprotein cholesterol level as compared to lard and olive oil diet groups (p < 0.05). The activity of liver acyl CoA:cholesterol acyltransferase (ACAT) of mice fed the SL diet was significantly lower than that of mice fed the lard or olive oil diet. A reduced formation of aortic fatty streak was observed in SL group. The extent of CLA incorporation depended on tissues or types of phospholipids. More CLA was incorporated in adipose tissue (1.85 mol %) than in the liver (0.33 mol %). Besides, more CLA was found in phosphatidylethanolamine (PE) (0.47 mol %) than in phosphatidylcholine (PC) (0.05 mol %) of hepatic phospholipids. Hepatic phospholipids (PC and PE) of mice fed the SL diet contained reduced contents of arachidonic and linoleic acid compared with mice fed the olive oil or lard diet. The present study suggests that SL could be considered as a functional oil for preventing risks of atheroscelerosis.

Hypocholesterolemic effect of physically refined rice bran oil: studies of cholesterol metabolism and early atherosclerosis in hypercholesterolemic hamsters.

Physically refined rice bran oil containing 2-4% nontriglyceride components as compared to other vegetable oils appears to be associated with lipid lowering and antiinflammatory properties in several rodent, primate and human models. These experiments were designed to investigate possible mechanisms for the hypocholesterolemic effect of the physically refined rice bran oil and to examine its effect on aortic fatty streak formation. In the first experiment, 30 hamsters were fed, for 8 weeks, chow-based diets plus 0.03% added cholesterol and 5% (wt/wt) coconut, canola, or physically refined rice bran oil (COCO, CANOLA or PRBO animal groups, respectively). Both plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly reduced in PRBO but not in CANOLA relative to COCO. PRBO also showed a significant 15-17% reduction in cholesterol absorption and significant 30% increase in neutral sterol (NS) excretion with no effect on bile acid (BA) excretion. Both CANOLA and PRBO showed a significant 300-500% increase in intestinal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and significant (>25%) decrease in hepatic HMG-CoA reductase activities with respect to COCO. In a second experiment, 36 hamsters were fed chow-based diets with 0.05% added cholesterol, 10% coconut oil and 4% additional COCO, CANOLA or PRBO. Relative to COCO and CANOLA, plasma TC and LDL-C were significantly reduced in PRBO. Early atherosclerosis (fatty streak formation) was significantly reduced (48%) only in PRBO, relative to the other two. These results suggest that the lipid lowering found in PRBO is associated with decreased cholesterol absorption, but not hepatic cholesterol synthesis, and that the decrease in fatty streak formation with this oil may be associated with its nontriglyceride components not present in the other two diets.

Dietary consumption of green tea catechins attenuate hyperlipidaemia-induced atherosclerosis and systemic organ damage in mice.

OBJECTIVE: The effects of consuming green tea catechins on the development of hyperlipidaemia-induced systemic organ damage have not been well studied; we investigated the effect using low density lipoprotein receptor knockout mice. METHODS AND RESULTS: Mice were treated with high cholesterol food containing 0.2 or 4% catechins and they were supplemented for 35 weeks. High plasma cholesterol levels, liver and renal dysfunctions were observed in no catechin fed mice, while chow containing catechin suppressed these levels and damages. Severe atherosclerosis of the aorta, fatty liver and renal injury were also shown in the control mice; inflammatory factors were enhanced in these lesions of nontreated mice. The lesions were attenuated with suppression of the inflammatory factors in the chow-contained catechin treatment group. CONCLUSION: Dietary consumption of tea catechins attenuated the development of the systemic organ damage; thus, this has a clinical effect against systemic inflammatory diseases.

Paradoxical effects of fenofibrate and nicotinic acid in apo E-deficient mice.

Atherosclerosis is a complex vascular disease initiated by abnormal accumulation of plasma lipoproteins in the subendothelial space. Elevated levels of plasma triglycerides (TG) and low-density lipoprotein (LDL)-cholesterol as well as low concentrations of high-density lipoprotein (HDL) play a causal role in the development and progression of atherosclerotic lesions. We have shown that apolipoprotein E-deficient (apo E-KO) mice have elevated triglyceride levels plus diminished HDL concentrations. Drugs such as fenofibrate and nicotinic acid are well known to reduce TG and increase HDL levels in humans. In this study, we investigated the beneficial effects of fenofibrate and niacin on lipid profile and atherogenesis in apo E-KO mice and their wild-type counterparts. Animals were fed with a cholesterol-enriched diet supplemented with fenofibrate (0.1% wt/wt, n = 8) or nicotinic acid (0.5% wt/wt, n = 8) for 14 weeks. Body weights were recorded weekly, and plasma lipid profiles were determined at 4-week intervals. The hearts and aortas were collected and fixed for histologic and morphometric evaluations of atherosclerotic lesions. Fenofibrate treatment in apo E-KO mice paradoxically increased total cholesterol and TG by 65% and 44%, respectively, and decreased HDL-cholesterol levels by 35% as compared with controls. Similar effects of fenofibrate on cholesterol levels, but not on TG concentrations, were observed in C57BL/6 mice. Fenofibrate-treated mice had lower body weight as compared with controls. Niacin had no effect on body weight gain but failed to decrease TG or to increase HDL levels in either apo E-KO mice or their wild-type counterparts. Neither fenofibrate nor niacin significantly influenced atherogenesis in apo E-KO mice as compared with controls. In conclusion, this study shows that neither niacin nor fenofibrate has beneficial lipid-modifying and antiatherosclerosis activities in mice. Identification of mechanisms underlying paradoxical effects of fenofibrate on lipoprotein metabolisms in apo E-KO mice merits further investigation.

Relationship of coffee consumption with risk factors of atherosclerosis in rats.

AIMS: In experimental animals we investigated the relationship of coffee consumption with risk factors of atherosclerosis such as cholesterol, homocysteine, oxidative stress and inflammatory cytokines. METHODS: Forty-eight male Wistar rats were assigned to 3 treatment groups (a control diet group, 0.62% coffee diet group, and 1.36% coffee diet group), and animals were maintained on the experimental diets for 140 days. RESULTS: Coffee diets led to an increase in the caffeine concentration to 0.53 +/- 0.11 and 1.77 +/- 0.22 microg/ml, respectively, although caffeine in serum was not detected in rats fed the control diet. It also led to slightly increased total serum levels of homocysteine and cholesterol, but no significant differences were found between the control and coffee diet groups. Coffee intake did not affect the production of IL-6 and TNF-alpha induced by LPS, which contributes to the atheroma-promoting effect of recurrent bacterial infection. Regarding the biomarkers of oxidative stress, the serum level of 15-isoprostane F(2t), which was significantly increased by LPS injection, was not altered by coffee intake. In contrast, urinary 8-hydroxy-2-deoxyguanosine was significantly increased in the coffee diet groups (p < 0.05). On the other hand, serum glutathione peroxidase (GPx) activity tended to decrease in the coffee groups compared with the control group, but no significant difference was found between the control and coffee diet groups. Interestingly, a significant negative correlation was observed between GPx activity and homocysteine levels in the sera from control and coffee diet groups (r = -0.403, p < 0.05). CONCLUSIONS: This report is the first animal study on the relationship of coffee consumption with risk factors for atherosclerosis. From these results, we conclude that moderate coffee intake is not a risk factor for atherogenesis.

Influence of alpha-linolenic acid and fish-oil on markers of cardiovascular risk in subjects with an atherogenic lipoprotein phenotype.

We tested the hypothesis that dietary alpha-linolenic acid (ALA) can exert effects on markers of cardiovascular risk similar to that produced by its longer chain counterparts in fish-oil. A dietary intervention study was undertaken to examine the effects of an ALA-enriched diet in 57 men expressing an atherogenic lipoprotein phenotype (ALP). Subjects were randomly assigned to one of three diets enriched either with flaxseed oil (FXO: high ALA, n = 21), sunflower oil (SO: high linoleic acid, n = 17), or SO with fish-oil (SOF n = 19) for 12 weeks, resulting in dietary intake ratios of n-6:n-3 PUFA of 0.5, 27.9 and 5.2, respectively. The relative abundance of ALA and EPA in erythrocyte membranes increased on the FXO diet (p < 0.001), whereas both EPA and DHA increased after fish-oil (p < 0.001). There were significant decreases in total plasma cholesterol within (FXO -12.3%, p = 0.001; SOF -7.6%, p = 0.014; SO -7.3%, p = 0.033) and between diets (p = 0.019), and decreases within diets after 12 weeks for HDL cholesterol on flaxseed oil (FXO -10%, p=0.009), plasma TG (-23%, p < 0.001) and small, dense LDL (-22% p = 0.003) in fish-oil. Membrane DHA levels were inversely associated with the changes in plasma TG ( p= 0.001) and small, dense LDL (p<0.05) after fish-oil. In conclusion, fish-oil produced predictable changes in plasma lipids and small, dense LDL (sdLDL) that were not reproduced by the ALA-enriched diet. Membrane DHA levels appeared to be an important determinant of these fish-oil-induced effects.

Protein tyrosine phosphatase LMW-PTP exhibits distinct roles between vascular endothelial and smooth muscle cells.

The present study examined the cellular functions of low-molecular-weight protein tyrosine phosphatase (LMW-PTP), which consists of two active isoforms IF-1 and IF-2, in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), focusing on cell growth and migration. We transduced recombinant IF-1 and IF-2, and ribozyme targeting both isoforms using an adenovirus vector in these cells. We detected the expression of IF-1 and IF-2 in both types of cells. IF-1 as well as IF-2 inhibited PDGF-induced DNA synthesis and migration in VSMCs. In contrast, both isoforms enhanced lysophosphatidic acid-stimulated cell migration without change in DNA synthesis in ECs. Whereas there is a report indicating that reactive oxygen species-dependent inactivation of LMW-PTP regulates actin cytoskeleton reorganization during cell spreading and migration, the isoforms conversely suppressed the PDGF-induced H2O2 generation with subsequent decrease in the p38 activity in VSMCs. Catalytically inactive LMW-PTP exerted the opposite and similar effects to the wild type in ECs and in VSMCs, respectively, suggesting that substrates for the phosphatase differ between these cells. Moreover, high concentrations of glucose suppressed the expression of LMW-PTP in both cells. These data suggest that LMW-PTP negatively regulates the pathogenesis of atherosclerosis and that glucose-dependent suppression of LMW-PTP expression may promote the development of atherosclerosis in diabetics.