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At least 649 records · Page 36Linked to original sources
PubMed2000

Control of vascular smooth muscle cell growth by cyclin-dependent kinase inhibitory proteins and its implication in cardiovascular disease.

While quiescence is a defining characteristic of differentiated vascular smooth muscle cells (VSMCs) residing within the medial layer of elastic arteries in the adult organism, mature VSMCs can undergo phenotypic modulation and reenter the cell cycle in response to several physiological and pathological stimuli. Abnormal VSMC proliferation is thought to contribute to the pathogenesis of vascular occlusive lesions, including atherosclerosis, vessel renarrowing after successful angioplasty (restenosis), and graft atherosclerosis after coronary transplantation. Therefore, elucidating the molecular mechanisms limiting VSMC growth is currently the subject of active research. This review will focus on the role of cyclin-dependent kinase inhibitory proteins in the regulation of VSMC proliferation and its implication in intimal lesion formation during the pathogenesis of vascular proliferative diseases.

Arteriosclerosis↗
PubMed1991

Time-related distribution profiles of sulfated glycosaminoglycans in cells, cell surfaces, and media of cultured rat liver fat-storing cells.

Fat-storing cells (perisinusoidal lipocytes, Ito cells), the principal proteoglycan-producing cell type in liver, were maintained for various times in primary and secondary culture to monitor the amount and pattern of [35S]sulfate-labeled glycosaminoglycans (GAG) in the cells, on the cell surface, and in the medium. In parallel with the phenotypic modulation of fat-storing cells toward myofibroblast-like cells, intracellular GAG decrease progressively, whereas cell surface-bound and medium GAG increase several-fold. These changes are associated with time-dependent alterations of the pattern of GAG in the various compartments. Dermatan sulfate is the most prominent intracellular GAG type in primary cultures, but on the cell surface and in the medium chondroitin sulfate prevails and reaches almost 70% of all medium GAG in secondary cultures. The results point to a highly dynamic expression of the specific types of GAG in the cellular and extracellular compartments of fat-storing cell cultures that seems to accompany the spontaneous transformation into myofibroblast-like cells. The latter one is a mainly chondroitin sulfate-producing cell type, whereas the initial fat-storing cell generates predominantly dermatan sulfate.

Animals↗
PubMed2003

[Supplementing Qi and activating blood circulation in gene regulation of vascular smooth muscle cells].

According to the theory of traditional Chinese medicine, blood stasis is a main pathological mechanism in the development of vascular diseases. Supplementing Qi and activating blood circulation, as the therapeutic principle for the blood stasis, has been adapted. Studies demonstrated that the supplementing Qi and activating blood circulation recipe could regulate the expression of vasoactive peptides in vascular smooth muscle cells (VSMCs). The recipe inhibited the formation of neointima following arterial intimal lesions through down-regulating expression of proliferation-related genes and phenotypic modulation of VSMCs. The recipe also markedly inhibited the adhesion and migration of VSMCs and matrix remodelling by means of a mechanism that balances extracellular matrix turnover rate. The purpose of this review is to summarize the recent advances made in our understanding of new functions for the recipe in regulating VSMCs behaviours and their microenvironment relevant to vascular diseases and maintaining proper homeostasis.

Cell Division↗
PubMed2004

Atherosclerosis and matrix dystrophy.

Atherosclerosis is characterized by inflammatory metabolic change with lipid accumulation in the artery. Atherosclerotic plaque occurs at discrete locations in the arterial system and involves the proliferation of smooth muscle cells (SMCs) together with imbalance of the extracellular matrix elements, elastic fiber in particular. The role of elastin in arterial development and disease was confirmed by generating mice that lack elastin. Thus, elastin is a critical regulatory molecule that regulates the phenotypic modulation, proliferation and migration of SMCs. We estimated that elastin expression and SMC proliferation are coupled inversely: potent stimulators of cell proliferation may potentially inhibit elastin expression and potent inhibitors of cell proliferation can stimulate elastin expression. Moreover, elastin was found to be expressed maximally at the G(0) and minimally at the G(2)/M phase during the cell cycle, suggesting that its expression is regulated by the cell growth state. The elastin peptide VPGVG enhanced SMC proliferation, resulting in the reduction of elastin expression. The inhibition of elastin expression by elastin fragments may be reflected in the negative feedback regulatory mechanism. The relationship between cell proliferation and elastin expression may be changed in atherosclerosis. Areas of atherosclerotic plaque show abnormality of elasticity and permeability from the viewpoint of the physiological function of the arterial wall. The etiology was estimated to be that cholesterol and calcium are deposited on the elastic fiber, resulting in decreased elastin synthesis and cross-linking formation. In addition, these dysfunctions of elastin fiber are also associated, in that the down-regulation of elastin and its related components (fibrillin-1 and lysyl oxidase) are directly related to calcification in SMCs. The denatured arterial elastin by cholesterol and calcium accumulation was also susceptible to proteolytic enzymes such as elastase and matrix metalloproteinase (MMP). Therefore, metabolic change in elastic fiber induces decreased elasticity and is associated with essential hypertension. Vitamin K(2) is used in drug therapy against atherosclerosis, or calcification in diabetes mellitus or dialysis, due to its promotion of the carboxylation of the matrix Gla protein.

Animals↗
PubMed1999

Inheritance in erythropoietic protoporphyria: a common wild-type ferrochelatase allelic variant with low expression accounts for clinical manifestation.

Erythropoietic protoporphyria (EPP) is a rare autosomal dominant disorder of heme biosynthesis characterized by partial decrease in ferrochelatase (FECH; EC 4.99.1.1) activity with protoporphyrin overproduction and consequent painful skin photosensitivity and rarely liver disease. EPP is normally inherited in an autosomal dominant pattern with low clinical penetrance; the many different mutations that have been identified are restricted to one FECH allele, with the other one being free of any mutations. However, clinical manifestations of dominant EPP cannot be simply a matter of FECH haploinsufficiency, because patients have enzyme levels that are lower than the expected 50%. From RNA analysis in one family with dominant EPP, we recently suggested that clinical expression required coinheritance of a normal FECH allele with low expression and a mutant FECH allele. We now show that (1) coinheritance of a FECH gene defect and a wild-type low-expressed allele is generally involved in the clinical expression of EPP; (2) the low-expressed allelic variant was strongly associated with a partial 5' haplotype [-251G IVS1-23T IVS2microsatA9] that may be ancestral and was present in an estimated 10% of a control group of Caucasian origin; and (3) haplotyping allows the absolute risk of developing the disease to be predicted for those inheriting FECH EPP mutations. EPP may thus be considered as an inherited disorder that does not strictly follow recessive or dominant rules. It may represent a model for phenotype modulation by mild variation in expression of the wild-type allele in autosomal dominant diseases.

Alleles↗
PubMed1999

Effects of proteasome and calpain inhibitors on the structural reorganization and proliferation of vascular smooth muscle cells in primary culture.

Vascular smooth muscle cells exhibit a striking plasticity and are able to change from a differentiated, contractile phenotype to a more immature, synthetic phenotype. This includes a prominent structural reorganization with loss of myofilaments and construction of a large secretory apparatus. As a result, the cells lose their contractility and become able to migrate, proliferate, and secrete extracellular matrix components. In vivo, this phenotypic shift is a chief factor behind the involvement of smooth muscle cells in formation of atherosclerotic and restenotic lesions. Here, the effects of the proteasome inhibitors carbobenzoxy-leucyl-leucyl-leucinal, N-acetyl-leucyl-leucyl-norleucinal, and lactacystin on the morphologic structure and growth of rat aortic smooth muscle cells in primary culture were examined. Electron microscopic analysis revealed that the volume density of myofilaments was higher and the volume density of the endoplasmic reticulum and the Golgi complex was lower in cells exposed to these drugs than in solvent-treated controls. Moreover, diffuse material representing incompletely degraded proteins gathered in the cytoplasm of exposed cells. Similar material was also found in lysosomes. Immunogold staining showed a positive reaction in the diffuse cytoplasmic aggregates with antibodies against ubiquitin-protein conjugates and proteasomes, whereas the material collecting in lysosomes reacted only with those against ubiquitin-protein conjugates. Moreover, weak staining for smooth muscle alpha-actin was noted in the cytoplasmic aggregates. Otherwise, reactivity for this protein was concentrated in myofilaments. In addition to the effects on cell structure described above, the proteasome inhibitors blocked cell multiplication. This was probably due to a decreased rate of transition into a synthetic state as well as direct interference with cell cycle progression in synthetic cells. These observations suggest that proteasomes have the major responsibility for protein degradation during transition of smooth muscle cells from a contractile to a synthetic phenotype. If proteasome activity is inhibited, undegraded material accumulates in the cytoplasm and is only partially taken up into lysosomes for digestion. These findings raise the possibility that proteasome inhibitors may have a beneficial effect on vascular pathologies associated with phenotypic modulation and proliferation of smooth muscle cells.

Actins↗
PubMed2000

Wound healing in the mitral valve.

BACKGROUND AND AIMS OF THE STUDY: Limited information is available on the healing of wounds in the mitral valve. In the present study, this process has been evaluated in young sheep. METHODS: Histologic, histochemical and transmission electron microscopic studies were made of the healing of wounds produced surgically under cardiopulmonary bypass, in the mitral valve (a 1 cm-long radially oriented incision at the free edge of the anterior leaflet) of young sheep (n = 11). RESULTS: All animals developed severe mitral regurgitation, as demonstrated by hemodynamic, ultrasound and ventriculographic studies. At four to five weeks, the edges of the incision were only partially covered by endothelium and had small deposits of fibrin. Two types of granulation tissue were associated with wound healing. The first covered the cut edge and consisted of myxoid tissue that extended from the valvular spongiosa and fibrosa; the second type consisted of spindle-shaped cells arranged parallel to the surface and surrounded by a slightly myxoid stroma. This granulation tissue resembled that caused by reactive fibrosis in regurgitant mitral valves. The connective tissue cells in granulation tissue developed increasing amounts of actin-like filaments as a function of time after operation. This differentiation resulted in the development of myofibroblasts. In contrast to the avascular nature of normal mitral leaflets, capillaries and arterioles first appeared in the middle portion of the leaflet at eight weeks, and at the proximal edges of the wounds at 12 weeks. CONCLUSION: The healing of mitral valvular wounds is a slow process that requires between eight and 12 weeks for the formation of a dense collagenous scar at the edges and complete restoration of the endothelial lining. Progression of healing is associated with the phenotypic modulation of connective tissue cells from fibroblasts to myofibroblasts and neovascularization of the leaflets.

Connective Tissue↗
PubMedDate not supplied

Culture of vascular cells in tridimensional (3-D) collagen: a methodological review.

Experimental models based on the culture of cells within tridimensional (3-D) gels add a 3-D organization to the classical 2-D culture of vascular cells. They allow the study of cell structure in an environment which is more representative of the in vivo situation and the investigation of cellular functions which cannot be studied using the basic 2-D models. This review shows examples of the use of cultures of vascular cells (endothelial cells, smooth muscle cells as well as fibroblasts) in 3-D collagen matrices for the study of cellular functions as diverse as angiogenesis, extracellular matrix reorganization, migration through 3-D collagen gels or phenotype modulation. It also describes recent advances in the in vitro reconstruction of biological blood vessels by bioengineering. A method for the preparation of 3-D collagen gels is described.

Cells, Cultured↗
PubMed2000

[Effect of heparinoid derived from porcine duodenum on the proliferation of cultured smooth muscle cells].

AIM: To study the antiproliferative effect of haparinoid derived from porcine duodenum (heparinoid) on cultured vascular smooth muscle cells. METHODS: Cultured bovine aortic smooth muscle cells (BASMCs) of 5-10 passages were seeded into 24 and 72-well cluster culture plates and were synchronized by 48 h serum deprivation. Then, the cells were re-stimulated by serum repletion with or without heparinoid. The antiproliferative effect of heparinoid was evaluated by crystal violet staining and MTT assay 72 h after serum repletion. To study the drug action on cytomorphological changes, three kinds of cells [quiescent cells, cells treated with 10% fetal calf serum (FCS) with or without heparinoid] were observed by transmission electron microscopy. After synchronized and re-stimulated as above, BASMCs were treated with heparinoid 0.8 mg.mL-1 at selected points during serum repletion. The cells were harvested at specified times after serum repletion, then cellular DNA contents (to estimate the proportions of cells in different phases of the cell cycle) and the contents of alpha-actin, c-myc and c-fos proteins were measured by flow cytometry. RESULTS: Heparinoid was shown to inhibit the proliferation of BASMCs induced by 10% FCS. The inhibitory effect was weakened when heparinoid was added 2 h after serum repletion, and there was no antiproliferative effect when heparinoid was added 12 h after serum repletion. Electron micrographs showed that cells treated with 10% FCS and heparinoid expressed a contractile phenotype, while cells treated with 10% FCS only expressed a synthetic phenotype. Flow cytometry study showed remarkable increase of alpha-actin, and decrease of c-myc and c-fos proteins in the cells treated with heparinoid. CONCLUSION: Heparinoid was found to inhibit the proliferation of BASMCs. The antiproliferative effect occurred at the early phase of the cell cycle. It might be due to the drug's influence on cell phenotype modulation and the down regulation of c-myc and c-fos proto-oncogenes expression.

Animals↗
PubMed2002

Variants of the microsomal triglyceride transfer protein gene are associated with plasma cholesterol levels and body mass index.

The microsomal triglyceride transfer protein (MTP) is required for the assembly and secretion of apolipoprotein B (apoB)-containing lipoproteins from liver and intestine. We set out to study the phenotypic modulation of all common genetic variants in the MTP gene. In addition, we aimed at characterizing the association between the various polymorphisms. A total of 564 healthy men were genotyped for the MTP -493 G/T, -400 A/T, and -164 T/C promoter polymorphisms, as well as the Q/H 95, I/T 128, Q/E 244, and H/Q 297 missense polymorphisms. The -493 G/T, -164 T/C, and I/T 128 polymorphisms showed to be in almost complete linkage disequilibrium. Subjects homozygous for the less common -493 T, -164 C, and T 128 alleles showed significantly lower plasma total and LDL cholesterol levels and plasma LDL apoB levels, and also significantly higher body mass index (BMI) and plasma insulin levels compared with carriers of the common alleles. The associations between plasma total cholesterol and MTP -493 genotype was verified in a cohort consisting of 1,117 disease-free control subjects of the West of Scotland Coronary Prevention Study (WOSCOPS). None of the other polymorphisms showed any significant change in either lipid and lipoprotein levels or anthropometric variables. In summary, two promoter polymorphisms and one missense polymorphism in the MTP gene alter plasma total and LDL cholesterol levels, plasma LDL apoB levels, BMI, and insulin levels. This may, in turn, have implications for genetic regulation of cardiovascular risk factors.

Alleles↗
PubMed1992

Analysis of the basis of resistance and susceptibility of CD4+ T cells to human immunodeficiency virus (HIV)-gp120 induced anergy.

The resistance and susceptibility of T cells to human immunodeficiency virus (HIV)-gp120 induced anergy was examined. Antigen-dependent proliferation of polyclonal T cells was markedly inhibited by gp120, whereas from the analysis of monoclonal populations, T cells resistant to the effects of gp120 could be identified. Similarly, exposure of monoclonal T cells to gp120 in the absence of accessory cells, also demonstrated that some T cells could resist the induction of anergy. Loss of antigen recognition was associated with phenotypic modulation of CD3 and CD28, which was not observed in T cells resistant to functional inactivation by gp120. Modulation of CD4 was not related to induction of anergy in the monoclonal T cells examined in this study. Inhibition of T-cell responses by anti-CD4 antibodies was compared to that by gp120. Anti-CD4 antibodies, which cross-compete with gp120 for binding to CD4, inhibited the response to antigen of monoclonal T cells. In contrast, no tolerogenic signals were delivered by pretreating T cells with the anti-CD4 antibodies in the absence of accessory cells, indicating that inhibition was due to abrogation of the interaction of CD4 with major histocompatibility complex (MHC) class II molecules expressed on accessory cells. Although the free CD4-binding region peptide of gp120 could inhibit polyclonal T-cell responses, only the carrier-bound peptide was able to modulate cloned T cells, suggesting a conformational requirement for functional inactivation through engagement of CD4. The results reported here using clonal CD4+ T-cell populations demonstrate that effects of gp120 on antigen-dependent proliferation are not uniform, and that therapeutic intervention might be directed at T-cell populations identified as susceptible to HIV-gp120 induced anergy.

Antigens, CD↗
PubMedDate not supplied

Modulation of differentiation-related responses in human colon carcinoma cells by protein kinase inhibitor H-7.

1-(isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), a potent inhibitor of protein kinases, has been used as a tool to examine the role of protein kinases in a variety of cellular functions. Contingent on the cell type, H-7 has been reported either to inhibit or to promote differentiation. The biological effects of H-7 on human colon adenocarcinoma cells have not been reported. In this study we investigated the effects of H-7 on differentiation - related parameters such as cellular morphology, proliferation, the expression of carcinoembryonic antigen (CEA), fibronectin and cytokeratins in human adenocarcinoma cell lines HCT116 and SW480. H-7 induced pronounced morphological alterations in both cell lines. It induced fibronectin expression and down-modulated CEA expression and secretion in the SW480 cells, but not in the HCT116 cells. Expression of acidic keratins was not affected by H-7 treatment in both cell lines. However, the expression of basic keratins were down-modulated in the HCT116 cells and enhanced in the SW480 cells. These studies showed that the protein kinase inhibitor, H-7, modulated phenotypic properties in human colon adenocarcinoma cells. Alterations in phenotypic properties and their significance in regard to the induction of differentiation are discussed.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2003

[Elevated expression of argentophilic proteins from the nucleolar organizer regions in myocardium of patients with obstructive hypertrophic cardiomyopathy and mutations in p53 tumor suppressor gene].

Silver staining for nucleolar proteins was used to evaluate the ribosomal genes activity in cardiomyocytes (Cm) and fibroblast-like cells (FBS) of intraventricular septum, and other regions of the left ventricle. Specimens to be analysed were taken from 7 patients with idiopathic obstructive hypertrophic cardiomyopathy (OHCM). In this group the quantity of nucleoli and AgNORs, reflecting the transcriptional and processing level of pre-ribosomal RNA in all type of cells, was at least 2 and 3 times higher than in patients with essential hypertension and in healthy control, respectively. We suggest that nucleolar hypertrophy in patients with hypertrophic cardiomyopathies, inappropriate to hypertrophy in other pathological conditions, may be most probably of compensatory character, and this may be in part explained by nuclear hyperploidy and chromosomal endoreduplication. We have noted a marked heterogeneity in shape, size and quantity of nucleoli, and in AgNORs of FBC. Nuclei with modulated phenotype containing nucleoli of high activity were revealed. This article presents the first data on p53 mutation identification in patients with advanced OHCM.

Adult↗
PubMed2004

Overexpression of c-met in oral SCC promotes hepatocyte growth factor-induced disruption of cadherin junctions and invasion.

Hepatocyte growth factor (HGF), the ligand for the c-met proto-oncogene product, is a multifunctional protein that enhances tumor cell motility, extracellular matrix invasion, and mitogenic or morphogenic activities of various cell types. In this study we examined the expression of the c-Met receptor in human oral squamous cell carcinoma (SCC) in vivo and in vitro to explore its relationship to tumor progression and invasiveness. Biopsy specimens of human oral SCC were immunohistochemically stained for c-Met. Nearly all primary oral SCC lesions and lymph node metastases consistently showed intense staining for c-Met, whereas normal oral mucosa showed faint to negative staining only on basal cells. In a panel of human oral SCC cell lines, we found a strong correlation between the levels of c-Met expression and the cells' response to HGF in motility and invasion assays. Sensitivity to HGF also correlated with the expression of the c-Met 9-kb mRNA. When the non-invasive HOC-605 cell line, which expresses a low level of c-Met receptor, was transfected with an expression plasmid containing human c-met cDNA, the transfectant cells showed motile and invasive responses to HGF. Immunostaining and immunoprecipitation studies demonstrated that E-cadherin and c-Met were physically associated at SCC cell-cell junctions, suggesting a direct role for c-Met in induction of junctional integrity. Importantly, HGF caused a rapid elevation of unbound beta-catenin, suggesting its availability for nuclear signal transduction and triggering of cell motility and invasiveness. Thus, overexpression of c-Met may facilitate disruption of E-cadherin junctions. Collectively, these results suggest that HGF/c-Met signaling is a common event in oral SCC that may trigger phenotype modulation and enhanced invasion and metastasis.

Blotting, Northern↗
PubMed2006

Inhibitory effects of polymyxin B on NF-kappaB activation and expression of procollagen I, III in pre-eclamptic umbilical artery smooth muscle cells.

BACKGROUND: It has been identified that in patients with pre-eclampsia, several factors were released into the serum, which can regulate the proliferation of vascular smooth muscle cells and stimulate the synthesis of extracellular matrix (ECM). However, the signal transduction pathway of the growth factors and cytokines synthesized by endothelial cells leading to the proliferation and ECM synthesis of human umbilical arterial smooth muscle cell (HUASMC) is unknown. The aim of this study was to research the effects of protein kinase C (PKC) inhibitor, polymyxin B (PMB), on the proliferation, nuclear factor-kappa B (NF-kappaB) activation, and expression of procollagen I and III mRNA in HUASMC cultured with pre-eclamptic umbilical sera. METHODS: Normal HUASMCs were treated with pre-eclamptic umbilical serum (pre-eclamptic group), pre- eclamptic umbilical serum plus PMB (PMB group), or normal umbilical serum (normal group). The expression of I-kappaB, NF-kappaB was detected by Western blotting after the HUASMC was incubated for 2 hours. The proliferation of HUASMC was evaluated by MTT, the cell cycle was analyzed by flow cytomerty, and the expression of procollagen I, III mRNA was measured by RT-PCR assay after HUASMC was incubated for 48 hours. ANOVA was used for statistical analysis. RESULTS: Umbilical sera in pre-eclampsia could stimulate the proliferation, the DNA synthesis, the transition of G(0) + G(1) phase or G(2)/M phase to S and phase, the activation of NF-kappaB, and the expression of procollagen I mRNA of HUASMC as compared with normal umbilical sera (P < 0.01). PMB could inhibit the proliferation, the DNA synthesis, the transition of G(0) + G(1) or G(2)/M phase phase to S phase, the activation of NF-kappaB, and the expressions of procollagen I mRNA of HUASMC stimulated by umbilical sera in pre-eclampsia (P < 0.01). CONCLUSION: PKC-NF-kappaB signal transduction pathway may play a key role in SMC phenotype modulation, which is more important in the pathogenesis of placental blood vessel in pre-eclampsia.

Cell Cycle↗
PubMed1990

Smooth muscle differentiation in scleroderma fibroblastic cells.

Using antibodies to alpha-smooth muscle actin and desmin on paraffin-embedded formalin-fixed tissue sections, the authors demonstrate that fibroblastic cells of localized and systemic scleroderma lesions express features of smooth muscle differentiation. Eleven of eleven skin specimens of systemic sclerosis patients and two of four skin specimens of localized scleroderma displayed the presence of fibroblasts expressing alpha-smooth muscle actin, a cell population that predominated in areas of prominent collagen deposition. A similar fibroblastic phenotype was found in the esophagus, the liver, and the lung specimens obtained from four patients who died of progressive systemic sclerosis. Immunostaining for desmin, performed on adjacent tissue sections, demonstrated that a minority of these fibroblastic cells present in skin and visceral lesions contained this protein. The authors' observations indicate that scleroderma fibroblasts are phenotypically related to the stromal cells previously identified in hypertrophic scars, fibromatoses, and desmoplasia; they might provide novel criteria for the characterization of scleroderma lesions and help to identify the factors responsible for phenotypic modulations in fibroblastic cells.

Cell Differentiation↗
PubMed1990

Induction of thrombospondin expression in vascular smooth muscle cells by angiotensin II.

Vascular smooth muscle cells (VSMCs), unlike cardiac or skeletal myocytes, are capable of undergoing reversible phenotypic modulation from "contractile" to "proliferative/synthetic" cells in vivo. We have investigated the ability of angiotensin II (Ang II) to influence this process via modulation of extracellular matrix synthesis. Ang II induced a rapid (within 2 h), dose (10(-6)-10(-9) M)-dependent stimulation (14-fold) of thrombospondin (TSP) gene expression in rat VSMCs in the absence of additional factors. This was followed by an enhanced platelet-derived growth factor (PDGF) A chain and transforming growth factor-beta (TGF beta) gene expression. These effects of Ang II could be negated by the simultaneous addition of saralasin (IC50 approximately 10(-9) M for Ang II at 10(-7) M) to cells. Transcription levels for TSP were further enhanced (to 28 X control values) by 6 h, at which time the synthesis of PDGF A chain mRNA was maximal. Although exposure of cells to TSP (5 X 10(-8) M) stimulated signal transduction pathways, it did not enhance levels of either PDGFA or TGF beta transcripts. The glycoconjugate content of extracellular matrices elaborated by cells chronically exposed to Ang II was elevated compared to control cultures and there was a small increase in cell number.

Angiotensin II↗
PubMed1991

[From cholesterol to lipoprotein particle markers and/or risk factors].

Among the risk factors for atherosclerosis, lipoproteins play a central role, particularly in the development of coronary artery disease. The plasma cholesterol level was the first definite indicator of the risk factor. Thereafter, technical progress has permitted the measurement of the cholesterol fractions, LDL cholesterol which is positively correlated with atherosclerosis, and HDL cholesterol, which is protective. However, the measurement of these fractions in a subject does not permit accurate determination of the risk to the subject. Likewise the measurement of apo A-I and B has brought an improvement in determining the risk factor but is still insufficient. The clarification of new markers would allow better definition of the potential atherogenic risk to a given individual Lp A-I (lipoproteins containing apo A-I but not apo A-II) level is probably an important indicator. Similarly, Lp(a) level is certainly an atherogenic lipoprotein and the apo E phenotype modulates the development of atherosclerosis. All these new markers and others, in the future, will better define the risk for an asymptomatic subject, with regard of atherosclerosis and therefore help to prevent it.

Arteriosclerosis↗