Exploring the mechanism of Danggui Buxue Decoction in regulating atherosclerotic disease network based on integrated pharmacological methods.

OBJECTIVE: To explore the mechanism of Danggui Buxue Decoction (DGBXD) in regulating Atherosclerosis (AS) network based on integrated pharmacological methods. METHODS: The active ingredients and targets of DGBXD are obtained from TCMSP database and ETCM. AS-related targets were collected from the Genecards and OMIM databases. The drug-disease protein interaction (PPI) networks were constructed by Cytoscape. Meanwhile, it was used to screen out densely interacting regions, namely clusters. Finally, Gene Ontology (GO) annotations are performed on the targets and genes in the cluster to obtain biological processes, and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations are performed on the targets of the PPI network to obtain signaling pathways. RESULTS: A total of 212 known targets, 265 potential targets and 229 AS genes were obtained. The 'DGBXD known-AS PPI network' and 'DGBXD-AS PPI Network' were constructed and analyzed. DGBXD can regulate inflammation, platelet activation, endothelial cell apoptosis, oxidative stress, lipid metabolism, vascular smooth muscle proliferation, angiogenesis, TNF, HIF-1, FoxO signaling pathway, etc. The experimental data showed that compared with the model group, the expressions of ICAM-1, VCAM-1, and interleukin (IL)-1ß protein and mRNA in the DGBXD group decreased (P<0.05). However, plasma IL-1ß, TNF-α, and MCP-1 in the DGBXD group were not significantly different from the model group (P>0.05). CONCLUSION: The mechanism of DGBXD in the treatment of AS may be related to the improvement of extracellular matrix (ECM) deposition in the blood vessel wall and the anti-vascular local inflammatory response, which may provide a reference for the study of the mechanism of DGBXD.

microRNA-155 Is Decreased During Atherosclerosis Regression and Is Increased in Urinary Extracellular Vesicles During Atherosclerosis Progression.

Background: Atherosclerosis is a chronic inflammatory disease driven by macrophage accumulation in medium and large sized arteries. Macrophage polarization and inflammation are governed by microRNAs (miR) that regulate the expression of inflammatory proteins and cholesterol trafficking. Previous transcriptomic analysis led us to hypothesize that miR-155-5p (miR-155) is regulated by conjugated linoleic acid (CLA), a pro-resolving mediator which induces regression of atherosclerosis in vivo. In parallel, as extracellular vesicles (EVs) and their miR content have potential as biomarkers, we investigated alterations in urinary-derived EVs (uEVs) during the progression of human coronary artery disease (CAD). Methods: miR-155 expression was quantified in aortae from ApoE-/- mice fed a 1% cholesterol diet supplemented with CLA blend (80:20, cis-9,trans-11:trans-10,cis-12 respectively) which had been previously been shown to induce atherosclerosis regression. In parallel, human polarized THP-1 macrophages were used to investigate the effects of CLA blend on miR-155 expression. A miR-155 mimic was used to investigate its inflammatory effects on macrophages and on ex vivo human carotid endarterectomy (CEA) plaque specimens (n = 5). Surface marker expression and miR content were analyzed in urinary extracellular vesicles (uEVs) obtained from patients diagnosed with unstable (n = 12) and stable (n = 12) CAD. Results: Here, we report that the 1% cholesterol diet increased miR-155 expression while CLA blend supplementation decreased miR-155 expression in the aorta during atherosclerosis regression in vivo. CLA blend also decreased miR-155 expression in vitro in human THP-1 polarized macrophages. Furthermore, in THP-1 macrophages, miR-155 mimic decreased the anti-inflammatory signaling proteins, BCL-6 and phosphorylated-STAT-3. In addition, miR-155 mimic downregulated BCL-6 in CEA plaque specimens. uEVs from patients with unstable CAD had increased expression of miR-155 in comparison to patients with stable CAD. While the overall concentration of uEVs was decreased in patients with unstable CAD, levels of CD45+ uEVs were increased. Additionally, patients with unstable CAD had increased CD11b+ uEVs and decreased CD16+ uEVs. Conclusion: miR-155 suppresses anti-inflammatory signaling in macrophages, is decreased during regression of atherosclerosis in vivo and is increased in uEVs from patients with unstable CAD suggesting miR-155 has potential as a prognostic indicator and a therapeutic target.

Probiotic supplementation attenuates hippocampus injury and spatial learning and memory impairments in a cerebral hypoperfusion mouse model.

Probiotics are referred to species of living microscopic organisms may help conserve the normal balance of the digestive system and/or manage diseases. A number of autoimmune, psychiatric, cardiovascular and cerebrovascular disorders may be associated with the imbalance of gut microbiota. This study examines the effect of 21 days consumption of multistrain probiotics on hippocampus injury, spatial and learning memory and some potential molecular mechanisms in a mouse model with cerebral hypoperfusion. Cerebral hypoperfusion was established in the mouse model by bilateral common carotid artery occlusion (BCCAO) for 20 min and 24 h reperfusion. Mixtures of several probiotic bacteria at concentrations of 107, 108 and 109 CFU/day were orally administrated for 3 weeks before the BCCAO. Spatial and learning memory, histological damage and apoptosis were assessed in the CA1, CA3 and dentate gyrus (DG) of the hippocampus 24 h after ischemia. The malondialdehyde (MDA) content and brain-derived neurotrophic factor (BDNF) level were measured by ELISA technique. Prophylactic of probiotic considerably reduced the number of apoptotic cells and neuronal death in the CA1, CA3 and DG of the hippocampus at all three concentrations (P < 0.001). In addition, probiotics reduced spatial memory impairment and neurological dysfunction only at the 109-CFU/day (P < 0.01). Nonetheless, probiotics did not change the levels of BDNF and MDA in the hippocampus (P > 0.05). According to the findings, the daily prophylactic ingestion of probiotics reduced hippocampus damage and prevented the spatial learning and memory deficit by suppressing apoptosis in the mouse model with cerebral hypoperfusion. Probiotic supplementation may be suggested as a useful preventive dietary strategy for groups susceptible to cerebrovascular diseases.

Molecular Alterations and Effects of Acute Dehydroepiandrosterone Treatment Following Brief Bilateral Common Carotid Artery Occlusion: Relevance to Transient Ischemic Attack.

Transient ischemic attack (TIA) represents brief neurological dysfunction of vascular origin without detectable infarction. Despite major clinical relevance characterization of post-TIA molecular changes using appropriate experimental model is lacking and no therapeutic agent has been established yet. Neurosteroid dehydroepiandrosterone (DHEA) arose as one of the candidates for cerebral ischemia treatment but its effects on TIA-like condition remain unknown. Seeking an animal model applicable for investigation of molecular alterations in mild ischemic conditions such as TIA, 15-min bilateral common carotid artery occlusion with 24-h reperfusion was performed to induce ischemia/ reperfusion (I/R) injury in adult male Wistar rats. Additionally, effects of 4-h post-operative DHEA treatment (20 mg/kg) were investigated in physiological and I/R conditions in hippocampus (HIP) and prefrontal cortex (PFC). The study revealed absence of sensorimotor deficits, cerebral infarcts and neurodegeneration along with preserved HIP and PFC overall neuronal morphology and unaltered malondialdehyde and reduced glutathione level following I/R and/or DHEA treatment. I/R induced nitric oxide burst in HIP and PFC was accompanied with increased neuronal nitric oxide synthase protein level exclusively in HIP. DHEA had no effects in physiological conditions, while increase of Bax/Bcl2 ratio and dissipation of mitochondrial membrane potential in treated I/R group suggested DHEA-mediated exacerbation of post-ischemic changes that might lead to pro-apoptotic events in HIP. Interestingly, DHEA restored I/R-induced NO to the control level in PFC. Obtained results indicated that I/R may serve as an appropriate model for investigation of molecular changes and treatment outcome following mild ischemic conditions such as TIA.

Resveratrol Regulates BDNF, trkB, PSA-NCAM, and Arc Expression in the Rat Cerebral Cortex after Bilateral Common Carotid Artery Occlusion and Reperfusion.

The polyphenol resveratrol (RVT) may drive protective mechanisms of cerebral homeostasis during the hypoperfusion/reperfusion triggered by the transient bilateral common carotid artery occlusion followed by reperfusion (BCCAO/R). This immunochemical study investigates if a single dose of RVT modulates the plasticity-related markers brain-derived neurotrophic factor (BDNF), the tyrosine kinase trkB receptor, Polysialylated-Neural Cell Adhesion Molecule (PSA-NCAM), and Activity-regulated cytoskeleton-associated (Arc) protein in the brain cortex after BCCAO/R. Frontal and temporal-occipital cortical regions were examined in male Wistar rats randomly subdivided in two groups, sham-operated and submitted to BCCAO/R. Six hours prior to surgery, half the rats were gavage fed a dose of RVT (180 mg·kg-1 in 300 µL of sunflower oil as the vehicle), while the second half was given the vehicle alone. In the frontal cortex of BCCAO/R vehicle-treated rats, BDNF and PSA-NCAM decreased, while trkB increased. RVT pre-treatment elicited an increment of all examined markers in both sham- and BCCAO/R rats. No variations occurred in the temporal-occipital cortex. The results highlight a role for RVT in modulating neuronal plasticity through the BDNF-trkB system and upregulation of PSA-NCAM and Arc, which may provide both trophic and structural local support in the dynamic changes occurring during the BCCAO/R, and further suggest that dietary supplements such as RVT are effective in preserving the tissue potential to engage plasticity-related events and control the functional response to the hypoperfusion/reperfusion challenge.

Altered brain volume and its relationship to characteristics of carotid plaques in asymptomatic patients.

Carotid plaque is an aggregate marker of exposure to vascular risk factors, which are linked to structural brain changes. We investigated prestroke global and regional changes in brain volume in a carotid plaque population of cognitively healthy individuals and the association between carotid plaque characteristics and these changes.A total of 76 participants were divided into healthy control (HC, n = 28), vulnerable plaque (n = 27) and stable plaque groups (n = 21). All subjects underwent carotid ultrasound and brain magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) was used to examine differences in regional gray matter volumes (rGMVs) among the different groups.The plaque group had a significantly lower mean total cerebral brain volume (TCBV) than the HC group (P = .03). Carotid intima-media thickness (CIMT) was negatively correlated with TCBV (r = -0.311, P = .006) and rGMV in the right thalamus (r = -0.589, P = .001). The rGMVs of the right middle occipital gyrus and bilateral lingual gyrus were significantly different between the unstable and stable groups. The gray-scale median (GSM) of the plaque and the total plaque risk score (TPRS) were correlated with the volume of the right middle occipital gyrus (r=-0.478, P = .001; r = 0.541, P = .001) and bilateral lingual gyrus (r = -0.419, P = .003; r = 0.288, P = .04).Carotid plaque is related to the volume of the brain parenchyma and right thalamus. The rGMVs of the right middle occipital gyrus and bilateral lingual gyrus differed between the vulnerable plaque and stable plaque groups, and the characteristics of carotid plaques may serve as indexes that reflect these changes.

Internal carotid artery aneurysm mimicking normal-tension glaucoma.

Differentiating glaucomatous from nonglaucomatous optic disc cupping remains challenging. We present a case of a 48-year-old woman with an internal carotid aneurysm of approximately 3.5 mm × 6.5 mm that mimicked normal-tension glaucoma. The patient had a 2-year history of low vision acuity in her left eye and frontal oppressive headache. Owing to the carotid aneurysm, she developed an asymmetric vertical cup-to-disc ratio above 0.2, and marked inferotemporal neuronal rim loss and pallor of the residual rim were noted in the left disc. She also developed a visual field defect with an arcuate scotoma in the left eye. The patient was referred to a neurosurgeon and underwent endovascular aneurysm occlusion. This case highlights the diagnostic importance of recognizing that many neurological defects remain underdiagnosed.

Internal carotid artery aneurysm mimicking normal-tension glaucoma / Aneurisma de carótida interna simulando glaucoma de pressão normal

ABSTRACT Differentiating glaucomatous from nonglaucomatous optic disc cupping remains challenging. We present a case of a 48-year-old woman with an internal carotid aneurysm of approximately 3.5 mm × 6.5 mm that mimicked normal-tension glaucoma. The patient had a 2-year history of low vision acuity in her left eye and frontal oppressive headache. Owing to the carotid aneurysm, she developed an asymmetric vertical cup-to-disc ratio above 0.2, and marked inferotemporal neuronal rim loss and pallor of the residual rim were noted in the left disc. She also developed a visual field defect with an arcuate scotoma in the left eye. The patient was referred to a neurosurgeon and underwent endovascular aneurysm occlusion. This case highlights the diagnostic importance of recognizing that many neurological defects remain underdiagnosed.

RESUMO diferenciação de escavações glaucomatosas e não glaucomatosas ainda permanece um desafio ainda nos dias de hoje. Nos descrevemos um caso de aneurisma de carótida interna medindo 3.5mm x 6.5mm que simulava um glaucoma de pressão normal. O caso é sobre uma paciente feminino de 48 anos com história de 2 anos de baixa acuidade visual no olho esquerdo e cefaléia frontal. Devido ao aneurisma de carótida a paciente desenvolveu uma assimetria de escavação vertical maior que 0.2 no olho esquerdo em relação ao direito com defeito localizado da camada de fibras nervosas temporal inferior. Ela também apresentava um defeito arqueado temporal superior a esquerda, cruzando a linha média vertical consistente. Após o diagnostico confirmado pela ressonância magnética funcional, a paciente foi enviada para o neurocirurgião para realização de uma oclusão endovascular do aneurisma. Esse caso nos alerta da importância de se lembrar que não apenas o glaucoma gera escavações suspeitas no disco óptico e que ainda muitos defeitos por causas neurológicas são subdiagnosticados.

Acute administration of beta-caryophyllene prevents endocannabinoid system activation during transient common carotid artery occlusion and reperfusion.

BACKGROUND: The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) has been shown to stimulate early molecular changes that can be easily traced in brain tissue and plasma, and that are indicative of the tissue physiological response to the reperfusion-induced oxidative stress and inflammation. The aim of the present study is to probe the possibility to prevent the molecular changes induced by the BCCAO/R with dietary natural compounds known to possess anti-inflammatory activity, such as the phytocannabinoid beta-caryophyllene (BCP). METHODS: Two groups of adult Wistar rats were used, sham-operated and submitted to BCCAO/R. In both groups, 6 h before surgery, half of the rats were gavage-fed with a single dose of BCP (40 mg/per rat in 300 µl of sunflower oil as vehicle), while the second half were pre-treated with the vehicle alone. HPLC, Western Blot and immunohistochemistry were used to analyze cerebral cortex and plasma. RESULTS: After BCCAO/R, BCP prevented the increase of lipoperoxides occurring in the vehicle-treated rats in both cerebral cortex and plasma. In the frontal cortex, BCP further prevented activation of the endocannabinoid system (ECS), spared the docosahexaenoic acid (DHA), appeared to prevent the increase of cyclooxygenase-2 and increased the peroxisome-proliferator activated receptor-alpha (PPAR-alpha) protein levels, while, in plasma, BCP induced the reduction of arachidonoylethanolamide (AEA) levels as compared to vehicle-treated rats. CONCLUSIONS: Collectively, the pre-treatment with BCP, likely acting as agonist for CB2 and PPAR-alpha receptors, modulates in a beneficial way the ECS activation and the lipoperoxidation, taken as indicative of oxidative stress. Furthermore, our results support the evidence that BCP may be used as a dietary supplement to control the physiological response to the hypoperfusion/reperfusion-induced oxidative stress.

Neuroprotective Effects of Electroacupuncture on an Animal Model of Bilateral Common Carotid Artery Occlusion.

Mild cognitive impairment (MCI) is considered as an intermediate zone between normal aging and dementia. The most prominent feature of MCI is an isolated mild decline in memory, whereas other cognitive functions remain intact. The symptoms of vascular cognitive impairment (VCI) range from MCI to dementia, and an animal model of VCI has been established in a gerbil by transient bilateral common carotid artery occlusion (BCCAO). In the current study, we set out to investigate whether electroacupuncture (EA) could improve memory in gerbils with BCCAO-induced MCI. Animals were randomly divided into two groups: sham-operated group (n = 17) and a model group that was subdivided into BCCAO, n = 17, and EA-treated BCCAO, n = 28. Gerbils were treated with EA at KI3 or GV20 four times every other day using a set of electrical stimulus pulses (1 mA, 2 Hz) that were applied for 20 min. For investigation of cognitive function, we performed a Y-maze test and Western blotting to identify the expression of neuroinflammatory proteins. EA treatment at KI3 ("Taegye" acupoint) improved cognitive function and reduced the expression of neuroinflammatory proteins including ionized calcium-binding adaptor molecule 1, toll-like receptor 4, tumor necrosis factor alpha, and phospho-extracellular signal-regulated kinase in the hippocampus of gerbils that had undergone BCCAO. Furthermore, using micro-positron emission tomography/computed tomography, we demonstrated that EA treatment increased glucose metabolism in the hippocampus of these animals. The present study highlights the neuroprotective effect of EA treatment against BCCAO-induced memory dysfunction, neuroinflammation, and glucose metabolism. Our findings suggest that EA, which has previously been used in complementary and alternative medicine, might also be considered as a therapy that can improve memory and reduce neuroinflammation associated with dementia.

Atorvastatin treatment and carotid plaque morphology in first-ever atherosclerotic transient ischemic attack/stroke: a case-control study.

BACKGROUND: A relationship between echolucency of carotid plaques and the consequent risk of ipsilateral ischemic stroke has been observed. An aggressive lipid-lowering therapy may increase the echogenicity of carotid plaque in patients with elevated low-density lipoprotein cholesterol levels. The aim of this study is to prospectively evaluate the long-term effect of high-dose atorvastatin on carotid plaque morphology in patients with first-ever transient ischemic attack or stroke. METHODS: All patients with symptomatic first ischemic atherosclerotic cerebrovascular event occurred within the previous 10 days were enrolled. Carotid Doppler ultrasound of the neck vessels with 7-11 MHz probe for the definition of the atherosclerotic carotid framework was performed. The analysis of the gray-scale median (GSM) of each plate was carried out with image processing software. RESULTS: A total of 240 symptomatic plaques were included and divided into 3 groups: 80 in group A (atorvastatin 80 mg), 80 in group B (atorvastatin 40 mg), and 80 to group C (no atorvastatin). GSM score increases significantly more extensive in group A than in group B (+48.65 vs. +39.46, P < .02) and group C (+48.65 vs. 19.3, P = .0002). An inverse association between reduction of low-density lipoprotein and the increase in the GSM score (r = -.456, P = .007) has been observed. Moreover, the reduction of high-sensitive C-reactive protein correlates inversely with the increase of the GSM (r = -.398, P = .021). CONCLUSIONS: Dose-dependent effect of atorvastatin on symptomatic carotid plaque morphology may suggest a specific role of this drug in the atherosclerotic stroke prevention.

Acetyl-L-carnitine normalizes the impaired long-term potentiation and spine density in a rat model of global ischemia.

As a consequence of an ischemic episode, energy production is disturbed, leading to neuronal cell death. Despite intensive research, the quest for promising neuroprotective drugs has largely failed, not only because of ineffectiveness, but also because of serious side-effects and dosing difficulties. Acetyl-l-carnitine (ALC) is an essential nutrient which plays a key role in energy metabolism by transporting fatty acids into mitochondria for ß-oxidation. It is an endogenous compound and can be used at high dose without toxicity in research into ischemia. Its neuroprotective properties have been reported in many studies, but its potential action on long-term potentiation (LTP) and dendritic spine density has not been described to date. The aim of the present study was an evaluation of the possible protective effect of ALC after ischemic insults inflicted on hippocampal synaptic plasticity in a 2-vessel occlusion (2VO) model in rats. For electrophysiological measurements, LTP was tested on hippocampal slices. The Golgi-Cox staining technique was used to determine spine density. 2VO resulted in a decreased, unstable LTP and a significant loss of dendritic spines. ALC administered after 2VO was not protective, but as pretreatment prior to 2VO it restored LTP nearly to the control level. This finding paralleled the histological analysis: ALC pretreatment resulted in the reappearance of dendritic spines on the CA1 pyramidal cells. Our data demonstrate that ALC administration can restore hippocampal function and spine density. ALC probably acts by enhancing the aerobic metabolic pathway, which is inhibited during and following ischemic attacks.

Leukotriene haplotype × diet interaction on carotid artery hypertrophy and atherosclerosis in American Indians: the Strong Heart Family Study.

OBJECTIVE: Gene × diet interaction plays an important role in atherosclerosis, an inflammatory disorder. Leukotrienes are the most potent inflammatory mediators, and genetic variants encoding leukotriene genes have been implicated in atherosclerosis. This study tests nutrigenetic interaction of a previously defined leukotriene haplotype on carotid artery hypertrophy and atherosclerosis in American Indians. METHODS: This study included 3402 American Indians participating in the Strong Heart Family Study (SHFS). Carotid artery measurements, including intima-media thickness (IMT), vascular mass, and plaque, were assessed using ultrasound. Eleven tagSNPs in the leukotriene A4 hydrolase (LTA4H) gene were genotyped in all subjects. Main haplotype effect and haplotype × diet interaction were examined by generalized estimating equation, adjusting for known risk factors. RESULTS: There was no significant main effect of haplotype or diet on any of the carotid artery measures. However, a previously defined LTA4H haplotype, called HapE, significantly interacted with dietary intake of n-3 and n-6 fatty acids on both IMT (P(HapE × n3) = 0.018, P(HapE × n6) = 0.040) and vascular mass (P(HapE × n3) = 0.012, P(HapE × n6) = 0.018), but not plaque. The direction of this nutrigenetic interaction on IMT was consistent with that reported in a recent study of Caucasian twins. CONCLUSION: Dietary intake of polyunsaturated fatty acids significantly modifies the effect of a leukotriene haplotype on carotid artery hypertrophy but not atherosclerosis in American Indians, independent of established cardiovascular risk factors. Replication of nutrigenetic interaction in two distinct ethnic groups suggests the robustness and generalizability of our findings to diverse populations.

Composition and genesis of calcium deposits in atheroma plaques.

The composition of atheromatous plaque determines its progression toward rupture or thrombosis. Although its histopathological structure has been widely studied, little attention has been paid to its structural and chemical composition and even less to its mineral component. Thirty-three atheromatous plaques were obtained by carotid thromboendarterectomy. Three types of materials were observed under polarized light microscopy: apatite crystals in the form of glomeruli (dark with plane polarized illumination and greensh with cross-polarized illumination); fibrous-like cholesterol (uncolored or grayish with plane-polarized illumination); and amorphous organic material as brownish deposits. SEM-EDX analysis showed an abundance of phosphorus and calcium in sufficient quantities to form calcium phosphates, and appreciably reduced levels of sodium. X-ray diffraction results differentiated samples into three groups: group I with predominance of hydroxyapatite-type crystals, group II with crystalline material containing an amorphous component, and group III with wholly amorphous material. The most abundant mineral in atheromatous plaque is hydroxyapatite, on which crystals of cholesterol and lipid nuclei are deposited, stratifying the plaque into layers that reflect the different stages of its formation. The difference in calcium and sodium concentrations between arteries with and without atheromata may indicate an important relationship in the pathophysiological development of calcium deposits.

The effects of 3 years of calcium supplementation on common carotid artery intimal medial thickness and carotid atherosclerosis in older women: an ancillary study of the CAIFOS randomized controlled trial.

Calcium is an essential nutrient for skeletal health; however, it has been suggested that supplemental calcium may be associated with adverse cardiovascular effects, raising widespread concern about their use. One suggested mechanism is via increasing carotid atherosclerosis, however few randomized controlled trials (RCT) of calcium supplements have assessed these mechanisms. The calcium intake fracture outcome study (CAIFOS) was a 5-year RCT (1998 to 2003) of 1.2 g of elemental calcium in the form of calcium carbonate in 1460 elderly women. An ancillary study of 1103 women assessed common carotid artery intimal medial thickness (CCA-IMT) and carotid atherosclerosis at year 3 (2001). The effects of supplementation were studied in intention-to-treat (ITT) and per-protocol (PP) analyses before and after adjustment for baseline cardiovascular risk factors. The mean age of participants at baseline was 75.2 ± 2.7 years. In ITT analyses, women randomized to calcium supplementation had no difference in multivariable-adjusted mean CCA-IMT (calcium 0.778 ± 0.006 mm, placebo 0.783 ± 0.006 mm, p = 0.491) and maximum CCA-IMT (calcium 0.921 ± 0.007 mm, placebo 0.929 ± 0.006 mm, p = 0.404). Women randomized to calcium did not have increased carotid atherosclerosis (calcium 47.2%, placebo 52.7%, p = 0.066). However, in women taking at least 80% of the supplements, a significant reduction in carotid atherosclerosis was observed in unadjusted but not in multivariate-adjusted models (p = 0.033 and p = 0.064, respectively). Participants in the highest tertile of total calcium (diet and supplements) had reduced carotid atherosclerosis in unadjusted and multivariable-adjusted analyses compared with participants in the lowest tertile (odds ratio [OR] = 0.67 [95% confidence interval (CI) 0.50-0.90], p = 0.008, and OR = 0.70 [95% CI 0.51-0.96], p = 0.028, respectively). In conclusion, these findings do not support the hypothesis that calcium supplementation increases carotid artery intimal medial thickness or carotid atherosclerosis, and high calcium intake may reduce this surrogate cardiovascular risk factor.

Effect of Ginkgo biloba on brain volume after carotid artery occlusion in rats: a stereological and histopathological study.

BACKGROUND/AIM: This study investigated the effect of Ginkgo biloba (GB) on brain volume in cerebral ischemia induced by stopping carotid artery blood flow. MATERIALS AND METHODS: Twenty-four adult male rats were divided into 4 groups of 6 rats each. No procedure was performed on the control group. Ischemia was applied to the rats in the ischemia and ischemia + GB groups by clamping the arteria carotis communis for 30 min. The rats in the ischemia + GB group were given 100 mg/kg drops (Tebokan Fort Drop, Abdi Ibrahim Ilaç Sanayi A.$., Turkey) containing dry GB leaf extract orally, every day for 14 days from the day of ischemia. In the sham group, surgical stress alone was applied by performing a skin incision. On the 14th day, brain tissues were extracted and evaluated stereologically and histopathologically. RESULTS: The only statistically significant difference was observed between the sham and control groups. CONCLUSION: This result may be interpreted as surgical stress, established by cutaneous incision, having an adverse effect on brain volume. Additionally, the absence of any difference in terms of brain volume following 30 min of ischemia between the ischemia and control groups suggests that a probable postischemic rise in brain volume disappears within 14 days.

Rate of change of carotid intima-media thickness with magnesium administration in Abcc6⁻/⁻ mice.

Pseudoxanthoma elasticum (PXE), caused by mutations in the ABCC6 gene, demonstrates progressive build-up of calcium phosphate and proteoglycans in the skin, eye, and arteries, and is associated to myocardial infarctions, stroke, blindness, and elevated carotid intima-media thickness (CIMT). Although CIMT reduction with magnesium (Mg) has been documented in a mouse model for PXE (Abcc6(-/-) ), it is not clear if Mg is effective in humans with PXE to reduce CIMT. To examine this, we calculated the rate of change of CIMT (washout) in 15- and 12-month-old Abcc6(-/-) mice fed standard rodent diet with or without Mg supplementation for 2 months. Using means in untreated 15- and 12-month-old Abcc6(-/-) mice (145 and 120 µm, respectively), the rate of change was 8.3 µm/month. Using means in treated 15- and 12-month-old Abcc6(-/-) mice (118 and 104.6 µm, respectively), the rate of change was 4.5 µm. Compared to normal progression of CIMT in humans without PXE, PXE has advanced atherosclerosis and possibly a higher CIMT rate of change. This experiment may portend, at least in PXE, the rationale for a 1-year oral Mg CIMT clinical trial and may be useful for application in other progressive mineralizing disorders like atherosclerosis.

[Effect of Shenlian extracts on blood flow and vessel pathological changes in rabbits carotid atherosclerosis model induced by low shear stress].

Lipid accumulation in the vessel wall and tunica intima vasorum pathological changes are important factors in the development of atherosclerosis, which are closely related with hemodynamics. In this paper, we established a model of local low shear stress in rabbits using carotid artery cannula and a high cholesterol diet for 2 weeks, 4 weeks and 8 weeks. The effects of Shenlian extract on blood flow, vascular pathology formation and lipid metabolism were assessed by electromagnetic blood flow meter and hematoxylin-eosin staining of the proximal end in carotid artery at different times. The results demonstrate that the relationship between blood flow and shear stress for control, atorvastatin, Shenlian extract high-dose, Shenlian extract middle-dose, and Shenlian extract low-dose were linearly related. The blood flow and the shear stress of proximal end in carotid artery of Shenlian extract (1.12, 2.24, 4.48 g x kg(-1)), and atorvastatin (4.7 x 10(-4) g x kg(-1)) were significantly (P < 0.05)increased compared with the control. Plasma total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) ,and high density lipoprotein cholesterol (HDL-C) were markedly decreased with the increasing of dose and time. This study is the first to prove that the inhibition of Shenlian extract on low shear stress (LSS) induces rabbits carotid atherosclerosis with increasing blood flow and decreasing lipids and vessel pathological changes.