Biomedical subjects

Akira Kitabatake

Publications and source records attributed to Akira Kitabatake.

At least 37 records · Page 2Linked to original sources

PubMed2005

Loss of insulin receptor substrate-1 signaling induces the cardiovascular and proteo(fibrino)lytic system derangements typical of insulin resistance.

BACKGROUND: Type 2 diabetes and insulin resistance have been associated with several cardiac features including diastolic heart failure, impaired ventricular function, perimicrovascular fibrosis and increased expression of plasminogen activator inhibitor type-1 (PAI-1) in coronary arterial walls. Insulin receptor substrate-1 (IRS-1) is one mediator of insulin signaling. This study was performed to determine whether induction of cardiac manifestations typical of insulin resistance and increased PAI-1 expression occur developmentally or post-developmentally as a result of loss of IRS-1-mediated signaling. METHODS: IRS-1 knockout mice were studied at 20 weeks of age. RESULTS: Compared with control mice, the left ventricular (LV) and cardiac mass to body weight ratios were increased. Diastolic and systolic LV diameters and decreased fractional shortening were indicative of LV dilatation and dysfunction. Coronary perimicrovascular fibrosis, an increased coronary arterial wall to lumen ratio, increased immunoreactivity of PAI-1 in the tunica media and increased PAI-1 mRNA expression were present consistent with constrained mural proteo(fibrino)lysis. These cardiac manifestations were similar to those we and others have observed previously in insulin-resistant mice without impaired IRS-1-mediated signaling. CONCLUSIONS: Loss of IRS-1 signaling is sufficient to induce cardiac manifestations typical of insulin resistance including increased coronary arterial mural PAI-1 expression. Furthermore, increased PAI-1 expression is not dependent on IRS-1 signaling.

Animals↗

PubMed2005

No positive association between adrenergic receptor variants of alpha2cDel322-325, beta1Ser49, beta1Arg389 and the risk for heart failure in the Japanese population.

AIMS: We investigated the correlation of adrenergic receptor polymorphisms, alpha(2c)Del322-325, beta(1)Ser49Gly and beta(1)Arg389Gly, with the risk of heart failure in the Japanese population. METHODS: These polymorphisms were analysed by polymerase chain reaction-restriction fragment length polymorphism in patients with chronic heart failure due to idiopathic dilated cardiomyopathy (DCM) and compared with the control group. RESULTS: There were no differences or any trends in the allele and genotype frequencies of the beta(1)Ser49Gly and beta(1)Arg389Gly polymorphisms. The allele frequency of the alpha(2c)Del322-325 variant was lower in patients than in controls (0.11 vs. 0.04, P = 0.011 < 0.017, by Bonferroni correction), while the genotype frequency just failed to reach significance (P = 0.022 > 0.017, by Bonferroni correction). CONCLUSIONS: In this population, the variants beta(1)Ser49, beta(1)Arg389, and alpha(2c)Del322-325 do not appear to be risk factors for chronic heart failure due to DCM. The alpha(2c)Del322-325 variant may in fact confer some protection.

Aged↗

PubMed2005

Chronic beta-adrenergic receptor stimulation enhances the expression of G-Protein coupled receptor kinases, GRK2 and GRK5, in both the heart and peripheral lymphocytes.

BACKGROUND: Enhanced expression of G protein-coupled receptor kinase (GRK) has been reported in failing hearts and in the present study the stability of enhanced GRK mRNA expression, and the correlation between the expression level of GRK mRNA in peripheral lymphocytes and in the heart were both evaluated. METHODS AND RESULTS: Isoproterenol was injected into rats for 2 weeks, and then GRK5 mRNA was assessed by quantitative reverse transcriptase-palymerase chain reaction. An enhanced expression of cardiac GRK5 mRNA was observed even after 4 weeks of recovery. The isoproterenol-induced increased expression of GRK2 and GRK5 mRNA was equally observed in the heart and lymphocytes, and there was a close correlation between the heart and lymphocytes in the level of expression of each GRK mRNA. CONCLUSIONS: The GRK mRNA level is maintained at a high level for a long period without continuous beta-adrenergic receptor stimulation. The level in circulating lymphocytes could be used as a surrogate marker to estimate the level of cardiac GRK expression and, presumably, the beta-adrenergic receptor function of cardiomyocytes.

Adrenergic beta-Agonists↗

PubMed2005

Mural thrombus in an ectatic right coronary artery caused acute myocardial infarction at downstream coronary artery.

A 72-year-old woman was admitted to our institution because of sudden chest pain. Emergency coronary angiography revealed thrombotic occlusion of the distal right coronary artery. A large cylindrical thrombus was retrieved from her distal right coronary artery using a thrombus aspiration catheter. IVUS showed minimal atherosclerosis and moderate ectatic change at the proximal right coronary artery. A reconstructed IVUS image also showed that a mural thrombus with abrupt ending was still retained at the ectatic segment. Based on this evidence, coronary ectasia was thought to be the primary cause for the thrombus formation and acute myocardial infarction in this case.

Aged↗

PubMed2005

Experimental studies on artificial blood usage for hemodilution during cardiopulmonary bypass.

BACKGROUND: Although hemodilution is usually utilized during cardiopulmonary bypass (CPB), hemodilution can cause adverse effects such as hypotension and hypoxia. The purpose of this study was to evaluate a novel perfluoro-octyl bromide (PFOB) emulsion, one of perfluorochemicals (PFCs) emulsions, administered during hemodilution CPB. METHODS: Fifteen dogs were subjected to CPB for 2 hours under mild hypothermia. Animals were divided into three groups; control group, hemodilution group and PFOB group. During the experiment, hemodynamics, complete blood count and blood chemistry were monitored. In addition, serum complement titer (CH50), bradykinin and histamine concentrations were also measured. RESULTS: Heart rate (HR) was markedly elevated in the hemodilution groups (p<0.05). Mean arterial pressure (MAP) did not change in the three groups. White blood cell (WBC) and platelet (PLT) count did not significantly differ among the three groups. Plasma lactate concentration was markedly elevated only in hemodilution group during late phase of CPB (p<0.05). In the hemodilution group, CH50, bradykinin and histamine, were markedly elevated during the CPB and just after CPB (p<0.05). CONCLUSIONS: The present study demonstrated possible benefits of the new PFC emulsion during cardiac surgery by counteracting the adverse effects of hemodilution during CPB.

Analysis of Variance↗

PubMed2004

An S-nitrosylated hemoglobin derivative protects the rat hippocampus from ischemia-induced long-term potentiation impairment with a time window.

Evidence suggests that S-nitrosylation is a biological process involved in cerebral ischemia. The aim of the present study was to elucidate the effects of S-nitrosylated (SNO) polyethylene glycol-conjugated (PEG) hemoglobin (Hb) developed as an artificial oxygen carrier, which can absorb free NO and translocate NO to a sulfhydryl (SH) moiety, on ischemic cerebral dysfunction. Long-term potentiation (LTP) in the perforant path-dentate gyrus synapses of the rat hippocampus was evaluated as functional outcome 4 days after transient incomplete cerebral ischemia (2-vessel occlusion: 2VO, 10 min). SNO-PEG-Hb (250 mg/kg, i.v.) administered on Day 0, 1, 2, or 4 (immediately, 24 h, 48 h, or 96 h after reperfusion, respectively) alleviated 2VO-induced LTP impairment with a therapeutic time window. The effect was significant when SNO-PEG-Hb was administered on Day 1 or 2. SNO-PEG-Hb altered NOS features observed in the vehicle-treated 2VO rat, upregulation of eNOS, nNOS, and iNOS expressions at mRNA and protein levels; SNO-PEG-Hb further upregulated eNOS and nNOS and downregulated iNOS expressions. These findings suggest that SNO-PEG-Hb might have protective effects on the rat hippocampus from ischemia/reperfusion-induced functional damages, thereby increasing the therapeutic potential as an artificial oxygen carrier for use in the area of oxygen therapy.

Animals↗

PubMed2004

Exposure to pressure stimulus enhances succinate dehydrogenase activity in L6 myoblasts.

Contraction of skeletal muscle generates pressure stimuli to intramuscular tissues. However, the effects of pressure stimuli, other than those created by electricity or nerve impulse, on physiological and biochemical responses in skeletal muscles are unknown. The purpose of this study is to examine the effects of a pure pressure stimulus on metabolic responses in a skeletal muscle cell line. Atmospheric pressure was applied to L6 myoblasts using an original apparatus. Succinate dehydrogenase (SDH) activity was evaluated by colorimetric assay using tetrazolium monosodium salt. The amounts of 2-deoxy-[(3)H]glucose uptake and lactate release were measured. SDH activity was 2.6- to 2.9-fold higher in pressurized L6 cells than in nonpressurized L6 cells (P < 0.01), and 2-deoxy-[(3)H]glucose uptake was 2.2-fold higher (P < 0.001). In addition, the amount of released lactate decreased from 6.8 to 3.7 mumol/dish when pressure was applied (P < 0.001). In contrast, the intracellular lactate contents of the pressurized cells were higher than those of nonpressurized cells (P < 0.01). However, the total amount of released lactate and intracellular lactate was lower in the pressurized cells than in nonpressurized cells. These findings demonstrate that a pure pressure stimulus enhances aerobic metabolism in L6 skeletal muscle cells and raise the possibility that elevated intramuscular pressure during muscle activity may be an important factor in stimulating oxidative metabolic responses in skeletal muscles.

Animals↗

PubMed2004

Can exercise training with weight loss lower serum C-reactive protein levels?

OBJECTIVE: C-reactive protein (CRP), an obesity-related inflammatory marker, is a promising predictor for cardiovascular disease and may be a mediator for atherogenesis. It has been reported that diet-induced weight loss lowered CRP levels. However, the effect of exercise training, another therapy that can reduce weight, on CRP is still unclear. We examined effects of exercise training with weight loss on CRP levels and conventional cardiovascular risks. METHODS AND RESULTS: A total of 227 apparently healthy women were recruited, and 199 subjects (average age 52 years) completed a 2-month weight reduction program consisting of supervised aerobic exercises. After the program, weight was reduced from 65.8 to 62.8 kg (P<0.0001), and all conventional variables were remarkably improved. Similarly, CRP levels were significantly decreased, from 0.63 (0.28 to 1.19) to 0.41 (0.18 to 0.80) mg/L (P<0.0001). However, in contrast to other variables, the changes in CRP levels were not proportionally associated with the extent of weight reduction. In the quartile analysis of % weight reduction, the largest weight reduction quartile did not show significant decreases in CRP levels, whereas moderate quartile showed remarkable CRP decreases. CONCLUSIONS: Exercise training with weight reduction disproportionately lowered CRP levels. Considering inflammatory status, there might be an optimal pace of exercise with weight loss.

C-Reactive Protein↗

PubMed2004

Gonadal hormones and frontocortical expression of vascular endothelial growth factor in male stroke-prone, spontaneously hypertensive rats, a model for attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (AD/HD) is a common pediatric behavioral disorder associated, in part, with male preponderance and reduced regional cerebral blood flow (rCBF). However, mechanism(s) underlying male preponderance and reduced rCBF in AD/HD are unclear. The present study profiles the expression of angiogenic and hormonal factors likely to underlie these symptoms using a recently characterized AD/HD animal model, juvenile male stroke-prone spontaneously hypertensive rats (SHRSP). Because vascular endothelial growth factor (VEGF) signaling cascade and gonadal steroids are key regulators of angiogenesis and gender-based behavior, respectively, we profiled their patterns of expression in the frontal cortex of SHRSP to elucidate their roles in the genesis of AD/HD male preponderance and rCBF. Interestingly, levels of VEGF, VEGF receptors (KDR, Flt-1), endothelial nitric oxide synthase, phosphorylated Akt (pAkt), estrogen receptor-alpha, aromatase, and capillary density in sham-operated SHRSP were remarkably down-regulated, whereas androgen receptor levels were up-regulated, compared with age-matched genetic control, Wistar-Kyoto rats. Castration, estrogen, and androgen receptor antagonist (flutamide) counteracted these effects. Dihydrotestosterone, but not testosterone, reversed the beneficiary effects of castration. Estrogen receptor-beta levels remained unchanged in all groups examined. We postulate that changes in androgen metabolism that tend to up-regulate local dihydrotestosterone concentration and diminish estrogen synthesis, in the frontal cortex of juvenile male SHRSP, may lower levels and/or activity of VEGF and its signaling cascade and, subsequently, reduce rCBF. These findings could, in part, help explain the pathogenesis of reduced rCBF and male preponderance in AD/HD.

Animals↗

PubMed2004

Role of osteopontin in cardiac fibrosis and remodeling in angiotensin II-induced cardiac hypertrophy.

Osteopontin (OPN) is upregulated in several experimental models of cardiac fibrosis and remodeling. However, its direct effects remain unclear. We examined the hypothesis that OPN is important for the development of cardiac fibrosis and remodeling. Moreover, we examined whether the inhibitory effect of eplerenone (Ep), a novel aldosterone receptor antagonist, was mediated through the inhibition of OPN expression against cardiac fibrosis and remodeling. Wild-type (WT) and OPN-deficient mice were treated with angiotensin II (Ang II) for 4 weeks. WT mice receiving Ang II were divided into 2 groups: a control group and an Ep treatment group. Ang II treatment significantly elevated blood pressure and caused cardiac hypertrophy and fibrosis in WT mice. Ep treatment and OPN deficiency could reduce the Ang II-induced elevation of blood pressure and ameliorate the development of cardiac fibrosis, whereas Ep-only treatment abolished the development of cardiac hypertrophy. Most compelling, the reduction of cardiac fibrosis led to an impairment of cardiac systolic function and subsequent left ventricular dilatation in Ang II-treated OPN-deficient mice. These results suggest that OPN has a pivotal role in the development of Ang II-induced cardiac fibrosis and remodeling. Moreover, the effect of Ep on the prevention of cardiac fibrosis, but not cardiac hypertrophy, might be partially mediated through the inhibition of OPN expression.

Aldosterone↗

PubMed2004

Natural killer T cells accelerate atherogenesis in mice.

We have investigated the potential role of CD1d-restricted natural killer T (NKT) cells in the development of atherosclerosis in mice. When fed an atherogenic diet (AD), NKT cell-deficient CD1d(-/-) mice had significantly smaller atherosclerotic lesions than AD-fed C57BL/6 (wild-type [WT]) mice. A significant reduction in atherosclerotic lesions was also demonstrated in AD-fed, low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice reconstituted with CD1d(-/-) bone marrow cells compared with the lesions observed in Ldlr(-/-)mice reconstituted with WT marrow cells. In addition, repeated injections of alpha-GalCer or the related glycolipid OCH to apolipoprotein E knockout (apoE(-/-)) mice during the early phase of atherosclerosis significantly enlarged the lesion areas compared with mice injected with vehicle control. However, administering alpha-GalCer to apoE(-/-) mice with established lesions did not significantly increase the lesion area but considerably decreased the collagen content. Atherosclerosis development in either AD-fed WT or apoE(-/-) mice was associated with the presence of Valpha14Jalpha18 transcripts in the atherosclerotic arterial walls, indicating that NKT cells were recruited to these lesions. Thioglycolate-elicited macrophages pulsed with oxidized low-density lipoproteins expressed enhanced CD1d levels and induced NKT cells to produce interferon-gamma, a potentially proatherogenic T-helper 1 (TH1) cytokine. Collectively, we conclude that NKT cells are proatherogenic in mice.

Animals↗

PubMed2004

Maladaptive arterial remodeling with systemic hypertension associated with increased concentrations in blood of plasminogen activator inhibitor type-1 (PAI-1).

Increased carotid artery intima-media thickness (IMT), but not necessarily peripheral vessel IMT, accompanies atherosclerosis. We hypothesized that IMT in a peripheral, muscular artery known to be resistant to atherosclerotic changes would increase with hypertension, thereby limiting increases in wall stress and potentially preserving endothelial cell function reflected by flow-mediated dilation (FMD). Plasminogen activator inhibitor type-1 (PAI-1) can inhibit vascular smooth muscle cell migration contributing to increased IMT. Thus, increased PAI-1 may attenuate the mural adaptive response. A high-resolution scanner designed to delineate brachial artery FMD and IMT was used in studies of previously untreated patients with essential hypertension (n = 18) and age- and gender-matched normotensive subjects (n = 15). Brachial IMT was increased with hypertension (0.36 +/- 0.07 vs 0.27 +/- 0.03 mm in controls, p <0.01), and FMD was lower (3.6 +/- 1.5% vs 7.8 +/- 3.6, p <0.01). PAI-1 antigen in blood was increased (40.5 +/- 31.8 vs 26.3 +/- 11.6 ng/ml, p <0.05). IMT and FMD correlated positively (r = 0.63, p <0.05) in hypertensive patients. FMD correlated inversely with wall stress (r = -0.57, p <0.05). IMT correlated inversely with PAI-1 (r = -0.61, p <0.05). These observations support the hypothesis that increased PAI-1 attenuated increases in neointimal vascular smooth muscle cell cellularity. Thus, increased PAI-1 may attenuate a mural, adaptive response to hypertension associated with preservation of endothelial cell function.

Carotid Arteries↗

PubMed2004

Low-dose carvedilol improves left ventricular function and reduces cardiovascular hospitalization in Japanese patients with chronic heart failure: the Multicenter Carvedilol Heart Failure Dose Assessment (MUCHA) trial.

BACKGROUND: The efficacy and optimum dose of beta-blockers have not been established in Japanese patients with chronic heart failure (CHF). The efficacy and safety of two doses of carvedilol, a beta-blocker with vasodilator and antioxidant actions, were investigated in Japanese patients with CHF. METHODS: After screening and a carvedilol challenge phase, 174 patients with mild to moderate CHF were randomly assigned (double-blinded) to placebo, 2.5 mg of carvedilol twice daily, or 10 mg of carvedilol twice daily. After a 2- to 4-week uptitration phase, maintenance treatment was continued for 24 to 48 weeks. The primary end point was improvement of the global assessment of CHF by the attending physician. Secondary end points were death or hospitalization for cardiovascular disease, cardiovascular hospitalization, hospitalization for heart failure, change of left ventricular ejection fraction, and change in New York Heart Association class. RESULTS: Carvedilol therapy achieved dose-dependent improvement of all end points (P for linear trend, range.002 to <.001). Both carvedilol groups showed marked risk reduction (71% to 91%) for cardiovascular and CHF hospitalization and for death or cardiovascular hospitalization (P range,.024 to <.001 for pairwise comparisons with placebo). No significant differences were observed for noncardiovascular hospitalization or adverse events. CONCLUSIONS: In Japanese patients with mild or moderate CHF, carvedilol achieved dose-related improvement of CHF and left ventricular ejection fraction; cardiovascular hospitalization was markedly reduced. At 5 mg/d, carvedilol conferred an important patient benefit, less than at 20 mg/d.

Adrenergic beta-Antagonists↗

PubMed2004

Salutary effects of attenuation of angiotensin II on coronary perivascular fibrosis associated with insulin resistance and obesity.

Obesity and insulin resistance confer increased risk for accelerated coronary disease and cardiomyopathic phenomena. We have previously shown that inhibition of angiotensin-converting enzyme (ACE) prevents coronary perimicrovascular fibrosis in genetically obese mice that develop insulin resistance. This study was performed to elucidate mechanism(s) implicated and to determine the effects of attenuation of angiotensin II (Ang) II. Genetically obese ob/ob mice were given ACE inhibitor (temocapril) or Ang II type 1 (AT(1)) receptor blocker (olmesartan) from 10 to 20 weeks. Cardiac expressions of plasminogen activator inhibitor (PAI)-1, the major physiologic inhibitor of fibrinolysis, and transforming growth factor (TGF)-beta(1), a prototypic profibrotic molecule, were determined and extent of perivascular coronary fibrosis was measured. Twenty-week-old obese mice exhibited increased plasma levels of PAI-1 and TGF-beta(1) compared with the values in lean counterpart. Perivascular coronary fibrosis in arterioles and small arteries was evident in obese mice that also showed increased left ventricular collagen as measured by hydroxyproline assay. Immunohistochemistry confirmed the deposition of perivascular type 1 collagen. Markedly increased PAI-1 and TGF-beta were seen immunohistochemically in coronary vascular wall and confirmed by western blotting. When obese mice were treated with temocapril or olmesartan from 10 to 20 weeks, both were equally effective and prevented increases in perivascular fibrosis, plasma PAI-1 and TGF-beta(1), left ventricular collagen and mural immunoreactivity for PAI-1, TGF-beta and collagen type 1. The c-Jun NH(2)-terminal kinase (JNK) activity was elevated in the left ventricle of obese mice (western) and blocked by temocapril and olmesartan. Ang II-mediated upregulation of PAI-1 and TGF-beta(1) with collagen deposition may explain the mechanism of perivascular fibrosis in obese mice. ACE inhibition and blockade of AT(1) receptor may prevent coronary perivascular fibrosis and collagen deposition even before development of overt diabetes. JNK activation may be a mediator of obesity-related cardiac dysfunction and a potential therapeutic target.

Angiotensin II↗

PubMed2004

Blockade of macrophage migration inhibitory factor ameliorates experimental autoimmune myocarditis.

Macrophage migration inhibitory factor (MIF) is a cytokine that plays a critical role in the regulation of macrophage effector functions and T-cell activation. However, its role in the pathogenesis of experimental autoimmune myocarditis (EAM) has remained unresolved. In this study, we studied the role of the MIF in EAM. We investigated the expression of MIF in EAM using enzyme-linked immunosorbent assay, Northern blotting, and immunohistochemistry. Moreover, a neutralizing antibody (Ab) to MIF was injected intraperitoneally from day 0 to 20 (experiment 1), or from day 13 to 19 (experiment 2), after the immunization. Disease severity was estimated by the macroscopic and microscopic findings for the heart, heart weight to body weight ratio, and cellular and humoral immune responses on day 21. Enhanced MIF protein and mRNA expression in the heart tissue and an elevated serum MIF concentration were confirmed in EAM. In experiment 1, the anti-MIF Ab treatment markedly inhibited the onset of EAM. Moreover, a significant reduction in disease severity was also achieved even after the delayed anti-MIF Ab treatment in experiment 2. Furthermore, we demonstrated that MIF blockade decreased the expression of VCAM-1, TNF-alpha, and IL-1beta and the migration of T-cells and macrophages in the EAM heart. These results demonstrate an important role of MIF in the pathogenesis of EAM and suggest that MIF blockade may be a promising new strategy for the treatment of myocarditis.

Animals↗

PubMed2004

A randomized, open-label, comparative study of simvastatin plus diet versus diet alone on angiographic retardation of coronary atherosclerosis in adult Japanese patients: Japanese utilization of simvastatin therapy (JUST) study.

BACKGROUND: Cholesterol-lowering therapy reduces the risk of cardiovascular events by slowing the progression or enhancing the regression of coronary atherosclerosis. OBJECTIVE: This study assessed the effects of simvastatin 10 mg/d on progressive coronary atherosclerosis in Japanese patients with coronary artery disease and mild to moderate hypercholesterolemia. METHODS: In a 2-year, open-label comparative study, patients with coronary atherosclerotic lesions (> or =50% diameter stenosis) and serum total cholesterol levels > or =200 and < or =280 mg/dL were randomly assigned to 2 groups: 1 group received simvastatin 10 mg/d taken orally with diet (S-D) and the other group was assigned to diet alone (D). Atherosclerotic progression in coronary segments was compared in the 2 groups using quantitative coronary angiography (QCA). QCA measurements were done under blinded conditions. The study's primary end point was the comparison of mean changes in each segment's minimum obstruction diameter (MOD) or mean segment diameter (MSD) between the S-D group and the D group. RESULTS: A total of 299 patients were randomized, 146 to the S-D group and 153 to the D group. Mean (SD) age was 58.7 (8.0) years and mean (SD) total cholesterol level was 232.6 (21.6) mg/dL at baseline. After 2 years, serum low-density lipoprotein cholesterol levels decreased by 31.9% in the S-D group and by 2.0% in the D group. QCA showed significant stenotic progression in the D group, with reductions in MOD and MSD both by per-segment-based (P < 0.001 and P = 0.004, respectively) and per-patient-based (both P = 0.004) analyses. Although simvastatin treatment suppressed atherosclerotic progression in both per-segment- and per-patient-based analyses, significant reductions were found only in MOD values with per-segment-based analyses (P = 0.034). In a categorical approach, progression was found in significantly fewer segments in the S-D group compared with the D group (MOD, P = 0.014; MSD, P = 0.003), with odds ratios (S-D) group/D group) of 0.571 for MOD and 0.390 for MSD. Significantly fewer patients with angiographic progression were observed in the S-D group (23.3%) compared with the D group (39.4%) with respect to MSD (P = 0.02). CONCLUSION: Two years of treatment with simvastatin 10 mg/d improved patients' lipid profile and retarded coronary atherosclerotic progression in Japanese patients with coronary artery disease and mild to moderate hypercholesterolemia

Anticholesteremic Agents↗

PubMed2004

Pure pressure stress increased monocarboxylate transporter in human aortic smooth muscle cell membrane.

Lactate is formed and utilized continuously under fully aerobic conditions. Lactate is oxidized actively at all times, especially during exercise. Family of monocarboxylate transport proteins (MCTs) that are differentially expressed in cells and tissues accomplishes the facilitated transport of lactate across membranes. Previously we reported that there is MCT1 in blood circulation. We also reported the pressure stress stimulated cell proliferation in aortic smooth muscle cells (HASMC). In this experiment we attempted to prove the existence of MCT1 in HASMC and to clarify the effect of pressure stress on MCT1 localization in HASMC. We determined succinate dehydrogenase (SDH) activity as a marker of energy metabolism in cells. SDH activity was increased by pressure stress. Lactate enhanced the SDH activity under pressure stress (160 mmHg for 3 h) as dose dependent manner. On the other hand, lactate excretion was suppressed by the addition of lactate. We could detect MCT1 in the cytosolic and the membrane fractions of HASMC. The pressure stress increased MCT1 in the membrane fraction in the presence of extracellular lactate. In summary, we proved the existence of MCT1 in HASMC. Pressure stress changed the localization of MCT1. The increased membranous MCT1 may transport lactate for energy metabolism in cells.

Aorta↗

PubMed2004

Regulatory molecules for coronary expressions of VEGF and its angiogenic receptor KDR in hypoestrogenic middle-aged female rats.

We studied the effects of estrogen deprivation and replacement on the protein and gene expression levels molecules that can be considered to be essential for coronary angiogenesis in middle-aged female rats. The animals were subjected to sham operation, ovariectomy, or ovariectomy with estrogen replacement therapy (ERT). Following ovariectomy, protein and gene expressions of vascular endothelial growth factor (VEGF) and its angiogenic receptor (KDR) showed a marked decline in coronary vessels, as determined by immunohistochemistry and in situ hybridization. ERT resulted in restoration of the ovariectomy-induced changes to intact levels. The coronary expression level of basic fibroblast growth factor was unaffected by estrogen deprivation or treatment. The changes in VEGF and KDR expressions were strongly associated with those in endothelial nitric oxide synthase (eNOS) expression in coronary vessels. Moreover, the age- and gender-dependent accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) protein appeared to be a determinant molecule of VEGF expression in middle-aged female rats. We reached a conclusion that the VEGF-KDR system plays a key role in coronary angiogenesis in hypoestrogenic elderly women and is critically regulated by estrogen, eNOS and HIF-1alpha.

Age Factors↗