Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Triterpenoids are natural compounds that are found in a large variety of plants and vegetarian foods, and are used for medicinal purposes in many Asian countries. Pentacyclic triterpenes, such as ursolic acid, have been reported to exhibit anticancer and anti-inflammatory properties. The present study was designed to assess the effects of ursolic acid in the migration and proliferation of vascular smooth muscle cells (VSMC), and in a vascular injury model. The exposure of VSMC to ursolic acid results in a chemotaxis inhibition, in a reduction of the expression of proliferating cell nuclear antigen (PCNA) and in a disorganization of beta-tubulin and vimentin cytoskeletal proteins. Administration of ursolic acid in the rat carotid balloon catheter injury model shows a significant inhibition of neointimal hyperplasia. Thus, we have demonstrated that daily doses of 6 mg/kg body weight for 10 days reduce both the ratio of intimal to medial areas and the degree of stenosis by 80%, and suppress the expression of PCNA in both neointima and media. These results suggest that pentacyclic triterpenes may be of potential therapeutic value in vascular injury, and a possible treatment strategy for the prevention of the progression of atherosclerosis and restenosis after angioplasty.
Atherosclerosis 2006 Jan
PMID:Ursolic acid inhibits neointima formation in the rat carotid artery injury model. 1592 47

Native low-density lipoprotein (LDL) and oxidized LDL (oxLDL) possess a wide variety of biological properties, and play a central role in atherogenesis. In this study, we used a proteomic analysis of human monocyte THP-1 cells induced with oxLDL or with LDL, to identify proteins potentially involved in atherosclerotic processes. Of the 2500 proteins detected, 93 were differentially expressed as a result of priming with LDL or oxLDL. The proteins were unambiguously identified by comparing the masses of their tryptic peptides with those of all known proteins using MALDI-TOF MS and the NCBI database. The largest differences in expression were observed for vimentin (94-fold increase), meningioma-expressed antigen 6 (48-fold increase), serine/threonine protein phosphatase 2A (40-fold increase), and beta-1,3-galactosyltransferase (15-fold increase). In contrast, the abundance of an unnamed protein product and phosphogluconate dehydrogenase decreased 30-fold and 25-fold, respectively. The expression of some selected proteins was confirmed by Western blot and RT-PCR analyses. The proteins identified in this study are attractive candidates for further biomarker research. This description of the altered protein profiles induced by oxLDL in human monocytes will support functional studies of the macrophage-derived foam cells involved in the pathogenesis of atherosclerosis.
 ...
PMID:Proteome analysis of human monocytic THP-1 cells primed with oxidized low-density lipoproteins. 1640 58

In the present study, we examined the effect of sympathectomy on the distribution and the relative expression of cytoskeletal proteins used as markers of phenotypic modulation of vascular smooth muscle cells (SMCs) and myofibroblasts (MFBs) in rabbit femoral (FA) and basilar (BA) arteries. Adult rabbits were treated either with repeated 6-hydroxydopamine (6-OHDA) for sympathectomy or with vehicle for control. Cross sections taken from sympathectomized and control arteries 79 days later were immunolabelled for vimentin, desmin, alpha-smooth muscle actin (alpha-SM actin), beta-isoform of actin and h-caldesmon. The distribution of these proteins and the intensity of fluorescent labelled SMCs were examined under a confocal microscope. In the sympathectomized BA, there was no change for desmin, vimentin and h-caldesmon expression, but the expression of both alpha-SM actin and the beta-isoform was significantly higher (+19% and +30%, respectively). In the sympathectomized FA, the expression of the alpha- and beta-isoforms of actin remained unchanged, whereas those of desmin and vimentin were significantly higher (+35% and 17%, respectively) and h-caldesmon expression was lowered by 13%. In contrast to intact FAs, the external layers of sympathectomized FAs revealed migration of fibroblasts from the adventitia and death of SMCs. These results strongly suggest that sympathetic nerves intervene in the cytoskeletal protein remodelling through phenotypic modulation of both SMCs and MFBs during post-natal development, and in pathologies involving similar phenomena, such as atherosclerosis.
 ...
PMID:Differing influence of sympathectomy on smooth muscle cells and fibroblasts in cerebral and peripheral muscular arteries. 1642 1

Previously [Histochem J 1997;29:279-286], we found that sympathectomy induced neointima formation in ear but not cerebral arteries of genetically hyperlipidemic rabbits. To clarify the influence of sympathetic nerves in atherosclerosis, and whether their influence involves vascular NO activity, we studied groups of normocholesterolemic intact (NI) and sympathectomized (NS), and hypercholesterolemic intact (HI) and sympathectomized (HS) rabbits (diet/6-hydroxydopamine for 79 days). Segments of basilar (BA) and femoral (FA) arteries were studied histochemically, to evaluate differentiation (anti-desmin, anti-vimentin, anti-h-caldesmon, and nuclear dye), by confocal microscopy, and by in vitro myography. In BAs, staining of NI and NS groups was similar. In hypercholesterolemic groups, a small neointima developed, more frequently in HS segments where smooth muscle cells (SMCs) positive for all antibodies appeared to be migrating into the neointima. In FAs, SMCs stained for the three antibodies in the NI group, but we observed desmin- and h-caldesmon-negative, vimentin-positive cells in some external medial layers of the NS, HI and HS groups, identical to adventitial fibroblasts. Large neointimas of the HS group contained vimentin-positive and largely desmin- and h-caldesmon-negative cells. Relaxation of BA or FA segments to acetylcholine was not decreased by sympathectomy. Sympathectomy increased the contraction of resting FAs to nitro-L-arginine (p = 0.0379). Thus, sympathectomy aggravates the tendency for FA SMCs to migrate and dedifferentiate, increasing atherosclerotic lesions, without decreasing NO activity, but has only minor effects on BAs.
 ...
PMID:Sympathectomy causes aggravated lesions and dedifferentiation in large rabbit atherosclerotic arteries without involving nitric oxide. 1665 46

Vascular adventitia is thought to change functions and contribute to diseases such as atherosclerosis, vascular restenosis, and fibrosis. To determine whether the adventitia contains mesenchymal stem/progenitor cells (MPCs), we cultured human vascular adventitial fibroblasts (hVAFs) from pulmonary arteries and analyzed their characteristics. The doubling time of the hVAFs was 1.5days, and the average number of passage was 11, which was independent of age and sex. The hVAFs were positive for vimentin, collagen type-1, CD29, CD44, and CD105, but negative for hematopoietic and endothelial cell markers. When hVAFs were cultured in appropriate media, they showed osteogenic and adipogenic differentiation by von Kossa, alkaline phosphatase, and oil red O staining. Myogenic differentiation was identified by increased expression of smooth muscle actin and calponin. These findings demonstrate that human vascular adventitia contains MPCs, and that hVAFs may be an ideal source for further experiments on stem cell biology and tissue engineering.
 ...
PMID:Human vascular adventitial fibroblasts contain mesenchymal stem/progenitor cells. 1823 Mar 45

In a previous study, we showed that after sympathectomy, the femoral (FA) but not the basilar (BA) artery from non-pathological rabbits manifests migration of adventitial fibroblasts (FBs) into the media and loss of medial smooth muscle cells (SMCs). The aim of the present study was to verify whether similar behaviour of arteries occurred in the pathological context of atherosclerosis. Thus, similar experiments were conducted on hypercholesterolemic rabbits, which were chemically sympathectomized with 6-hydroxydopamine (n=4) or treated with vehicle for control (n=5). Cross-sections of BA and FA were immunolabelled for five markers of phenotypic modulation of vascular SMCs and FBs: vimentin, desmin, alpha-smooth muscle actin, beta-isoform of actin, and h-caldesmon and examined using a confocal microscope. Also, 3D images were constructed and morphometric analysis performed using image analysis software. Both intact and sympathectomized BA and FA developed atherosclerotic plaques, but the thickening of the intima was more advanced in sympathectomized animals, as judged by increased plaque frequency and by the phenotypic modulation of SMCs in the intima. Our results show that in the media of FAs hypercholesterolemia induces changes similar to those observed in sympathectomized rabbits in non-pathological conditions, i.e., migration of adventitial FBs to the media and loss of medial SMCs. These latter changes, which can be ascribed to pathological events, were accentuated after sympathectomy in the hypercholesterolemic rabbits. The present study reveals that pathological events, including migration and phenotypic modulation of vascular FBs and loss of SMCs, may be under the influence of sympathetic nerves.
 ...
PMID:Similar pathological effects of sympathectomy and hypercholesterolemia on arterial smooth muscle cells and fibroblasts. 1837 68

There is increasing evidence suggesting that oxidized low-density lipoproteins (ox-LDL) play a critical role in endothelial injury contributing to the age-related physio-pathological process of atherosclerosis. In this study, the effects of native LDL and ox-LDL on the mechanical properties of living human umbilical vein endothelial cells (HUVEC) were investigated by atomic force microscopy (AFM) force measurements. The contribution of filamentous actin (F-actin) and vimentin on cytoskeletal network organization were also examined by fluorescence microscopy. Our results revealed that ox-LDL had an impact on the HUVEC shape by interfering with F-actin and vimentin while native LDL showed no effect. AFM colloidal force measurements on living individual HUVEC were successfully used to measure stiffness of cells exposed to native and ox-LDL. AFM results demonstrated that the cell body became significantly stiffer when cells were exposed for 24 h to ox-LDL while cells exposed for 24 h to native LDL displayed similar rigidity to that of the control cells. Young's moduli of LDL-exposed HUVEC were calculated using two models. This study thus provides quantitative evidence on biomechanical mechanisms related to endothelial cell dysfunction and may give new insight on strategies aiming to protect endothelial function in atherosclerosis.
 ...
PMID:Oxidized-LDL induce morphological changes and increase stiffness of endothelial cells. 1869 95

Neointima formation participates in the pathophysiology of atherosclerosis and restenosis. Proliferation and migration of vascular smooth muscle cells (VSMC) are initial responses to vascular injury. The aim of the present study was to assess the effect of gliotoxin, an inhibitor of nuclear factor (NF)-kappaB, on migration and proliferation of cultured rat VSMC and neointimal formation in injured rat vessels. In cultured VSMC, gliotoxin inhibited the nuclear translocation of the p65 subunit of NF-kappaB in response to inflammatory stimuli. In addition, gliotoxin inhibited VSMC migration and proliferation in response to platelet-derived growth factor-BB. This was associated with a rapid rearrangement of the F-actin and vimentin cytoskeleton. Furthermore, gliotoxin inhibited endothelial cell nuclear translocation of p65, cell surface expression of adhesion molecules such as VCAM-1, ICAM-1 and E-selectin, and monocytic cell adhesion to a cytokine-activated endothelial monolayer. In the rat carotid artery balloon catheter injury model, the systemic administration of gliotoxin for 10 days decreased neointimal hyperplasia and luminal stenosis by up to 90% and decreased the expression of proliferating cell nuclear antigen in the vessel wall by up to 70%, depending on the dose. These observations suggest that gliotoxin favorably regulates the response to vascular injury through actions on VSMC. However, further studies evaluating the therapeutic benefit of gliotoxin in restenosis after balloon angioplasty are required.
 ...
PMID:Gliotoxin inhibits neointimal hyperplasia after vascular injury in rats. 1903 90

Hyperhomocysteinemia is a common independent risk factor for cardiovascular diseases. The promoting effect of homocysteine (Hcy) on vascular smooth muscle cell (VSMC) proliferation has been considered as one of the important pathological bases of atherosclerosis. However, the mechanism of VSMC proliferation induced by Hcy remains unclear. The present research used proteomic techniques to globally analyze the protein changes in proliferative VSMCs. After comparing the protein expression profiles of VSMCs between the Hcy-treated and non-treated groups, 11 protein spots were found altered markedly in proliferative VSMCs with expression of eight protein spots increased and three protein spots decreased. In the differentially expressed proteins, eight protein spots were identified successfully including glycolytic metabolism proteins: pyruvate kinase M2 (PKM2), triosephosphate isomerase (TPI) and aldose reductase (AR); cytoskeletal proteins: lamin C and vimentin; and three other proteins: calreticulin; similar to WDR1 protein and LIM and SH3 protein 1. The differentially expressed proteins were further validated by Western blot and confirmed by assay of enzymes' activities and ATP content. These results may provide some clues for comprehensively understanding the mechanism of VSMC proliferation and pathogenesis of atherosclerosis induced by Hcy.
 ...
PMID:Proteomic analysis of homocysteine induced proliferation of cultured neonatal rat vascular smooth muscle cells. 1903 67

The invasion of monocytes through the endothelial wall of arteries and their transformation from macrophage into form cells has been implicated as a critical initiating event in atherogenesis. Human THP-1 monocytic cells can be induced to differentiate into macrophages by phorbol myristate acetate (PMA) treatment, and can be converted into foam cells by exposure to oxidized low-density lipoprotein (oxLDL). To identify proteins potentially involved in atherosclerotic processes, we performed a proteomic analysis of THP-1 macrophages exposed to oxLDL generated by treatment with native LDL with hypochlorous acid/hypochlorite (HOCl/OCl(-)). We detected more than a thousand proteins, of which 104 differentially expressed proteins were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) and the NCBI database. The largest differences in expression were observed for bifunctional purine biosynthesis protein, vacuolar protein sorting 33A, breast carcinoma amplified sequence, adenine phosphoribosyltransferase, and tropomyosin alpha 3 chain. Interestingly, many apoptotic proteins such as lamin B1, poly (ADP-ribose) polymerase, Bcl-2 related protein A1 and vimentin were identified by MALDI-TOF analysis. Identities were confirmed by matching the sequence of several tryptic peptides using MALDI-TOF/TOF MS, Western blot analyses and immunofluorescent microscopy. The data described here will contribute to establishing a functional profile of the human macrophage proteome. Furthermore, the proteins identified in this study are attractive candidates for further biomarkers involved in the pathogenesis of atherosclerosis.
 ...
PMID:Proteomic analysis of human macrophages exposed to hypochlorite-oxidized low-density lipoprotein. 1910 13


<< Previous 1 2 3 4 5 6 Next >>