Endothelial dysfunction and atherosclerosis

Pm, Vanhoutte

doi:10.1016/s0195-668x(97)90005-1

Cited by 185 publications

(104 citation statements)

References 80 publications

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“…Endothelial dysfunction is one of the first hallmarks in the pathogenesis of atherosclerosis [23]. Sattar et al [24] and Toikka et al [25] reported that endothelial dysfunction is related to a specific lipoprotein profile, which is characterized by a substantially decreased concentration of HDL.…”

Section: Discussionmentioning

confidence: 99%

Indoxyl Sulfate and Atherosclerotic Risk Factors in Hemodialysis Patients

Tsuruta²,

2007

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Background: Indoxyl sulfate is a uremic toxin that accelerates the progression of chronic kidney disease (CKD). Serum levels of indoxyl sulfate are increased in dialysis patients. It was reported that indoxyl sulfate plays a role in endothelial dysfunction in uremic patients, and stimulates proliferation of rat vascular smooth muscle cells (VSMC). We examined associations between indoxyl sulfate and several markers related to atherosclerosis. Methods: The association between indoxyl sulfate and atherosclerotic risk factors was studied in 224 hemodialysis (HD) patients (123 male, 101 female). Serum levels of indoxyl sulfate were measured by using high-performance liquid chromatography (HPLC). Results: There were significant differences in serum levels of creatinine, calcium × phosphate and pentosidine between high- and lowindoxyl sulfate level groups. Indoxyl sulfate showed significant positive correlations with pentosidine, creatinine, and protein catabolic rate, and a significant negative correlation with high-density lipoprotein (HDL) cholesterol. Further, pentosidine, creatinine, and HDL-cholesterol were independently associated with indoxyl sulfate by multiple linear regression analysis. Conclusion: In addition to creatinine, pentosidine and HDL-cholesterol, the risk factors of atherosclerosis, were associated with indoxyl sulfate in HD patients. Indoxyl sulfate may be involved in the pathogenesis of atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Indoxyl Sulfate and Atherosclerotic Risk Factors in Hemodialysis Patients

Tsuruta²,

2007

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“…Circulating serotonin is a potent biogenic amine that exhibits strong vasoactive properties [27,28], possibly through stimulation of serotonin receptors on endothelial cells and nitric oxide production [29,30]. Serotonin uptake into platelet dense granules protects the mammalian organism from serotonin-induced uncontrolled, harmful vasoconstriction or vasodilation [31]. Recently, serotonin synthesis was blocked by the disruption of the nonneuronal tryptophan hydroxylase 1 gene (tph1-/-) in mice.…”

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confidence: 99%

Circulating serotonin in vertebrates

Maurer‐Spurej

2005

CMLS, Cell. Mol. Life Sci.

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The role of circulating serotonin is unclear and whether or not serotonin is present in the blood of non-mammalian species is not known. This study provides the first evidence for the presence of serotonin in thrombocytes of birds and three reptilian species, the endothermic leatherback sea turtle, the green sea turtle and the partially endothermic American alligator. Thrombocytes from a fresh water turtle, American bullfrog, Yellowfin tuna, and Chinook salmon did not contain serotonin. Serotonin is a vasoactive substance that regulates skin blood flow, a major mechanism for endothermic body temperature regulation, which could explain why circulating serotonin is present in warm-blooded species. The temperature sensitivity of human blood platelets with concomitant changes in serotonin content further supports a link between circulating serotonin and thermoregulation. Phylogenetic comparison of the presence of circulating serotonin indicated an evolutionary divergence within reptilian species that might coincide with the emergence of endothermy.

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“…However, the mechanisms by which plasma membrane ER␣ initiate signaling events remain unresolved (12). The best-described agonists for eNOS, acetylcholine and bradykinin, activate specific plasma membrane-associated G protein-coupled receptors (GPCR) (13,14). G proteins are heterotrimers of ␣, ␤, and ␥ subunits (G␣␤␥), which dissociate into G␣ and G␤␥ upon GPCR stimulation, and activated G␣ and/or G␤␥ then modulate the activity of downstream effector molecules.…”

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confidence: 99%

Plasma Membrane Estrogen Receptors Are Coupled to Endothelial Nitric-oxide Synthase through Gαi

Wyckoff¹,

Chambliss²,

Mineo³

et al. 2001

Journal of Biological Chemistry

275

177

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Estrogen causes rapid endothelial nitric oxide (NO) production because of the activation of plasma membrane-associated estrogen receptors (ER) coupled to endothelial NO synthase (eNOS). In the present study, we determined the role of G proteins in eNOS activation by estrogen. Estradiol-17␤ (E 2 , 10 ؊8 M) and acetylcholine (10 ؊5 M) caused comparable increases in NOS activity (15 min) in intact endothelial cells that were fully blocked by pertussis toxin (Ptox). In addition, exogenous guanosine 5-O-(2-thiodiphosphate) inhibited E 2 -mediated eNOS stimulation in isolated endothelial plasma membranes, and Ptox prevented enzyme activation by E 2 in COS-7 cells expressing ER␣ and eNOS. Coimmunoprecipitation studies of plasma membranes from COS-7 cells transfected with ER␣ and specific G␣ proteins demonstrated E 2 -stimulated interaction between ER␣ and G␣ i but not between ER␣ and either G␣ q or G␣ s ; the observed ER␣-G␣ i interaction was blocked by the ER antagonist ICI 182,780 and by Ptox. E 2 -stimulated ER␣-G␣ i interaction was also demonstrable in endothelial cell plasma membranes. Cotransfection of G␣ i into COS-7 cells expressing ER␣ and eNOS yielded a 3-fold increase in E 2 -mediated eNOS stimulation, whereas cotransfection with a protein regulator of G protein signaling, RGS4, inhibited the E 2 response. These findings indicate that eNOS stimulation by E 2 requires plasma membrane ER␣ coupling to G␣ i and that activated G␣ i mediates the requisite downstream signaling events. Thus, novel G protein coupling enables a subpopulation of ER␣ to initiate signal transduction at the cell surface. Similar mechanisms may underly the nongenomic actions of other steroid hormones.The hormone estrogen classically exerts its effects by modifying gene expression through the action of estrogen receptors that serve as transcription factors (1). There are also important nongenomic actions of estrogen in a variety of tissues including bone, mammary gland, pituitary gland, neuron, ovary, and vasculature (2-5). We and others have previously shown that estrogen acutely stimulates the endothelial isoform of nitric oxide synthase (eNOS) 1 by mechanisms that are nongenomic yet mediated by estrogen receptor ␣ (ER␣) (6 -8).Recent studies demonstrate that there is a subpopulation of ER␣ localized to the endothelial cell plasma membrane in caveolae, where it functions in a signaling module with eNOS (9). Involvement of the tyrosine kinase-MAP kinase signaling pathway has been implicated in the mechanism of ER-mediated eNOS activation (8), and very recent work supports a role for the recruitment of the PI3-kinase-Akt pathway that may entail direct interaction between ER␣ and the p85 subunit of PI3-kinase (10, 11). However, the mechanisms by which plasma membrane ER␣ initiate signaling events remain unresolved (12). The best-described agonists for eNOS, acetylcholine and bradykinin, activate specific plasma membrane-associated G protein-coupled receptors (GPCR) (13,14). G proteins are heterotrimers of ␣, ␤, and ␥ subunits (G␣␤␥), which...

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Endothelial dysfunction and atherosclerosis

Cited by 185 publications

References 80 publications

Indoxyl Sulfate and Atherosclerotic Risk Factors in Hemodialysis Patients

Indoxyl Sulfate and Atherosclerotic Risk Factors in Hemodialysis Patients

Circulating serotonin in vertebrates

Plasma Membrane Estrogen Receptors Are Coupled to Endothelial Nitric-oxide Synthase through Gαi

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