scholarly journals Tongqiaohuoxue Hinders Development and Progression of Atherosclerosis: A Possible Role in Alzheimer’s Disease

Biology ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 363
Author(s):  
Eunyoung Ha ◽  
Mikyung Kim ◽  
Jaemoo Chun ◽  
Chang-Seob Seo ◽  
YouMee Ahn ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adhesion Molecule ◽  
Cell Activation ◽  
Intercellular Adhesion Molecule ◽  
In Vitro Assays ◽  
High Cholesterol Diet ◽  
Therapeutic Effects ◽  
Endothelial Cell Activation ◽  
Progression Of Atherosclerosis

Atherosclerosis is closely associated with Alzheimer’s disease (AD). Tongqiaohuoxue decoction (THD) is a classical herbal prescription in traditional Chinese medicine widely used for the prevention and treatment of cerebrovascular disease. This study aimed to explore the therapeutic effects of THD on atherosclerosis and AD. Eight-week-old C57BL6/J wild-type and ApoE-deficient (ApoE-/-) mice were fed a high-fat and high-cholesterol diet for eight weeks, followed by oral phosphate-buffered saline vehicle or THD treatment for eight weeks further. In ApoE-/- mice, THD attenuated lipid deposition in the aorta and the brain, and abrogated atherosclerotic changes without affecting serum lipid profiles while decreasing amyloid plaque formation. In vitro assays undertaken to understand THD’s effects on lipid clearance in the aorta and brain vessels revealed that THD treatment inhibited the lipid uptake, stimulated by oxidized low-density lipoprotein, resulted in decreased endothelial cell activation through reduction in intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and monocyte chemoattractant protein-1 levels. Serum analysis revealed inhibitory effects of THD on resistin production, which has important roles in the development of both atherosclerosis and AD. In conclusion, the current study demonstrates beneficial effects of THD on the development and progression of atherosclerosis, and a possible protective role against AD.

scholarly journals Peripheral Markers of Vascular Endothelial Dysfunction Show Independent but Additive Relationships with Brain-Based Biomarkers in Association with Functional Impairment in Alzheimer’s Disease

2021 ◽  
pp. 1-13
Author(s):  
Jonathan D. Drake ◽  
Alison B. Chambers ◽  
Brian R. Ott ◽  
Lori A. Daiello ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Functional Impairment ◽  
Amyloid Β ◽  
Intercellular Adhesion Molecule ◽  
Csf Biomarkers ◽  
Linear Regression Models ◽  
Cognitively Normal

Background: Cerebrovascular dysfunction confers risk for functional decline in Alzheimer’s disease (AD), yet the clinical interplay of these two pathogenic processes is not well understood. Objective: We utilized Alzheimer’s Disease Neuroimaging Initiative (ADNI) data to examine associations between peripherally derived soluble cell adhesion molecules (CAMs) and clinical diagnostic indicators of AD. Methods: Using generalized linear regression models, we examined cross-sectional relationships of soluble plasma vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-Selectin to baseline diagnosis and functional impairment (clinical dementia rating sum-of-boxes, CDR-SB) in the ADNI cohort (n = 112 AD, n = 396 mild cognitive impairment (MCI), n = 58 cognitively normal). We further analyzed associations of these biomarkers with brain-based AD biomarkers in a subset with available cerebrospinal fluid (CSF) data (n = 351). p-values derived from main effects and interaction terms from the linear regressions were used to assess the relationship between independent and dependent variables for significance (significance level was set at 0.05 a priori for all analysis). Results: Higher mean VCAM-1 (p = 0.0026) and ICAM-1 (p = 0.0189) levels were found in AD versus MCI groups; however, not in MCI versus cognitively normal groups. Only VCAM-1 was linked with CDR-SB scores (p = 0.0157), and APOE ɛ4 genotype modified this effect. We observed independent, additive associations when VCAM-1 and CSF amyloid-β (Aβ 42), total tau, phosphorylated tau (P-tau), or P-tau/Aβ 42 (all <  p = 0.01) were combined in a CDR-SB model; ICAM-1 showed a similar pattern, but to a lesser extent. Conclusion: Our findings indicate independent associations of plasma-based vascular biomarkers and CSF biomarkers with AD-related clinical impairment.

scholarly journals Active Targeted Nanoemulsions for Repurposing of Tegaserod in Alzheimer’s Disease Treatment

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1626
Author(s):  
Line Séguy ◽  
Léna Guyon ◽  
Manon Maurel ◽  
Pascal Verdié ◽  
Audrey Davis ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Vitro Assays ◽  
Titration Calorimetry ◽  
Therapeutic Effects ◽  
Disease Treatment ◽  
Cellular Effects ◽  
Irritable Bowel ◽  
The Stability

Background and Purpose: The activation of 5-HT4 receptors with agonists has emerged as a valuable therapeutic strategy to treat Alzheimer’s disease (AD) by enhancing the nonamyloidogenic pathway. Here, the potential therapeutic effects of tegaserod, an effective agent for irritable bowel syndrome, were assessed for AD treatment. To envisage its efficient repurposing, tegaserod-loaded nanoemulsions were developed and functionalized by a blood–brain barrier shuttle peptide. Results: The butyrylcholinesterase inhibitory activity of tegaserod and its neuroprotective cellular effects were highlighted, confirming the interest of this pleiotropic drug for AD treatment. In regard to its drugability profile, and in order to limit its peripheral distribution after IV administration, its encapsulation into monodisperse lipid nanoemulsions (Tg-NEs) of about 50 nm, and with neutral zeta potential characteristics, was performed. The stability of the formulation in stock conditions at 4 °C and in blood biomimetic medium was established. The adsorption on Tg-NEs of peptide-22 was realized. The functionalized NEs were characterized by chromatographic methods (SEC and C18/HPLC) and isothermal titration calorimetry, attesting the efficiency of the adsorption. From in vitro assays, these nanocarriers appeared suitable for enabling tegaserod controlled release without hemolytic properties. Conclusion: The developed peptide-22 functionalized Tg-NEs appear as a valuable tool to allow exploration of the repurposed tegaserod in AD treatment in further preclinical studies.

Expression of intercellular adhesion molecule 1 (ICAM-1) in Alzheimer's disease

1991 ◽  
Vol 106 (1) ◽  
pp. 105-111 ◽  
Author(s):  
Elliot M. Frohman ◽  
Teresa C. Frohman ◽  
Sudhir Gupta ◽  
Antonin de Fougerolles ◽  
Stanley van den Noort
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adhesion Molecule ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1

Circulating Endothelial Cell/Leukocyte Adhesion Molecules in Atherosclerosis

1994 ◽  
Vol 72 (01) ◽  
pp. 151-154 ◽  
Author(s):  
Andrew D Blann ◽  
Charles N McCollum
Keyword(s):  
Endothelial Cell ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Activation ◽  
Leukocyte Adhesion ◽  
Clinical Manifestations ◽  
Intercellular Adhesion Molecule ◽  
Endothelial Cell Activation ◽  
Soluble Adhesion Molecules ◽  
Von Willebrand

SummarySoluble adhesion molecules E-selectin, intercellular adhesion molecule (sICAM) and vascular cell adhesion molecule (sVCAM) were measured alongside von Willebrand factor (vWf) in 40 patients with peripheral vascular disease (PVD), 43 with ischaemic heart disease (IHD) and in equal numbers of age and sex matched asymptomatic controls. Increased vWf was found in patients with IHD (p = 0.0008) and in patients with PVD (p = 0.0001) relative to their respective controls but levels did not differ between the two patient groups. Raised sICAM was found in both PVD (p = 0.0003) and IHD (p = 0.0059) compared to their respective controls and was higher in PVD than in IHD (p = 0.0088). In the subjects taken as a whole, there was no correlation between vWf and sICAM. Levels of soluble E-sel-ectin and sVCAM did not differ in patients or controls. These data suggest that soluble ICAM may be useful as an index of endothelial cell activation in clinical manifestations of atherosclerosis.

scholarly journals Synthetic Colloids Attenuate Leukocyte-Endothelial Interactions by Inhibition of Integrin Function

2005 ◽  
Vol 103 (4) ◽  
pp. 759-767 ◽  
Author(s):  
Boris Nohé ◽  
Tanja Johannes ◽  
Jörg Reutershan ◽  
Albert Rothmund ◽  
Helene A. Haeberle ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Cell Activation ◽  
Tissue Injury ◽  
Severe Infection ◽  
Intercellular Adhesion Molecule ◽  
Neutrophil Adhesion ◽  
Intercellular Adhesion Molecule 1 ◽  
Endothelial Cell Activation

Background It has been suspected that synthetic colloids may interfere with leukocyte adhesion by down-regulation of endothelial cell adhesion molecules. Although inhibition of endothelial inflammation might reduce leukocyte-related tissue injury, the same mechanism may be detrimental for host defense during severe infection. Regarding the widespread use of colloids, the authors performed a laboratory investigation to determine the mechanisms by which synthetic colloids interfere with leukocyte-endothelial interactions. Methods Adhesion molecule expression on native and cytokine-activated endothelium from umbilical veins was measured after pretreatment with gelatin and various preparations of dextran or hydroxyethyl starch. Inhibition of neutrophil adhesion to activated endothelium was examined in a flow chamber by perfusion of untreated and colloid-treated neutrophils over colloid-pretreated endothelium at 2 dyn/cm. Comparisons were made between untreated controls, colloid-pretreated endothelium, and colloid-cotreated neutrophils. Results Intercellular adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin, and P-selectin were not attenuated by any colloid. Accordingly, colloid pretreatment of endothelium alone did not reduce neutrophil adhesion. In contrast, when neutrophils were cotreated by addition of colloids to the perfusate immediately before perfusion, adhesion decreased by 31-51% (P &lt; 0.05) regardless of the colloid type. As indicated by the twofold increased rolling fractions, this reduction was due to an inhibition of neutrophil integrins. Conclusions This study shows that synthetic colloids inhibit neutrophil adhesion by a neutrophil-dependent mechanism rather than interfering with endothelial cell activation. This suggests that inhibition of leukocyte sequestration by volume support is a common and transient phenomenon depending on the colloid concentration in plasma.

Intercellular adhesion molecule-1 K469E gene polymorphism and Alzheimer’s disease

2003 ◽  
Vol 24 (2) ◽  
pp. 385-387 ◽  
Author(s):  
Roberto Pola ◽  
Andrea Flex ◽  
Eleonora Gaetani ◽  
Angelo Santoliquido ◽  
Michele Serricchio ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Polymorphism ◽  
Adhesion Molecule ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1

scholarly journals Endothelial cell activation leads to neutrophil transmigration as supported by the sequential roles of ICAM-2, JAM-A, and PECAM-1

Blood ◽  
2009 ◽  
Vol 113 (24) ◽  
pp. 6246-6257 ◽  
Author(s):  
Abigail Woodfin ◽  
Mathieu-Benoit Voisin ◽  
Beat A. Imhof ◽  
Elisabetta Dejana ◽  
Britta Engelhardt ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Cell Activation ◽  
Intercellular Adhesion Molecule ◽  
Dependent Manner ◽  
Wild Type ◽  
Endothelial Cell Activation ◽  
Leukocyte Transmigration ◽  
Ability To Act ◽  
Tnf Α

Abstract Leukocyte transmigration is mediated by endothelial cell (EC) junctional molecules, but the associated mechanisms remain unclear. Here we investigate how intercellular adhesion molecule-2 (ICAM-2), junctional adhesion molecule-A (JAM-A), and platelet endothelial cell adhesion molecule (PECAM-1) mediate neutrophil transmigration in a stimulus-dependent manner (eg, as induced by interleukin-1β [IL-1β] but not tumor necrosis factor-α [TNF-α]), and demonstrate their ability to act in sequence. Using a cell-transfer technique, transmigration responses of wild-type and TNF-α p55/p75 receptor-deficient leukocytes (TNFR−/−) through mouse cremasteric venules were quantified by fluorescence intravital microscopy. Whereas wild-type leukocytes showed a normal transmigration response to TNF-α in ICAM-2−/−, JAM-A−/−, and PECAM-1−/− recipient mice, TNFR−/− leukocytes exhibited a reduced transmigration response. Hence, when the ability of TNF-α to directly stimulate neutrophils is blocked, TNF-α–induced neutrophil transmigration is rendered dependent on ICAM-2, JAM-A, and PECAM-1, suggesting that the stimulus-dependent role of these molecules is governed by the target cell being activated. Furthermore, analysis of the site of arrest of neutrophils in inflamed tissues from ICAM-2−/−, JAM-A−/−, and PECAM-1−/− mice demonstrated that these molecules act sequentially to mediate transmigration. Collectively, the findings provide novel insights into the mechanisms of action of key molecules implicated in leukocyte transmigration.

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