Disease relevance of Pericytes

• More importantly, the defects in blood flow recovery, clinical manifestations of ischemia, ischemic reserve capacity, and pericyte recruitment into the growing neovasculature can be rescued by local intramuscular delivery of an adenovirus encoding a constitutively active allele of eNOS, eNOS S1179D, but not a control virus [1].
• We identified regulator of G-protein signaling-5 (RGS-5) as an angiogenic pericyte marker at sites of physiologic and pathologic angiogenesis [2].
• These findings suggest that endothelin is a regulator of the contractile properties of pericytes, which may be adversely affected in diabetic retinopathy [3].
• The effect of aminoguanidine and tolrestat on glucose toxicity in bovine retinal capillary pericytes [4].
• In multiple sclerosis, infiltrating lymphocytes did not express C3aR, but a strong staining was detected on smooth muscle cells (pericytes) surrounding blood vessels [5].

Psychiatry related information on Pericytes

• CONCLUSIONS: The results indicate that impaired glucose metabolism may influence one of the defense mechanisms for oxidative stress, but also suggest that decreased glutathione levels occur prior to morphological signs of pericyte loss and/or endothelial cell proliferation in this animal model of hereditary NIDDM [6].

High impact information on Pericytes

• This study revealed that the participation of Pdgfrb(-/-) cells in all muscle lineages (smooth, cardiac, skeletal and pericyte) was reduced by eightfold compared with Pdgfrb(+/+) cells, and that participation of Pdgfrb(+/-) cells was reduced by twofold (eightfold for pericytes) [7].
• Pericyte loss and microaneurysm formation in PDGF-B-deficient mice [8].
• Here we show that integrin alpha4beta1 (VLA-4) and VCAM-1 promote close intercellular adhesion between ECs and pericytes and that this interaction is required for blood vessel formation [9].
• Antagonists of this integrin-ligand pair block the adhesion of mural cells to proliferating endothelia in vitro and in vivo, thereby inducing apoptosis of ECs and pericytes and inhibiting neovascularization [9].
• In contrast, a kinase inhibitor incorporating selectivity for PDGFRs (SU6668) is shown to block further growth of end-stage tumors, eliciting detachment of pericytes and disruption of tumor vascularity [10].

Chemical compound and disease context of Pericytes

• As early as 2 days after hyperglycemia was induced, an increased apoptosis of endothelial cells and pericytes was detected by transferase-mediated deoxyuridine triphosphate nick-end labeling assay and electron microscopy [11].
• CONCLUSIONS: The results suggest that palmitate could induce apoptotic cell death in microvascular EC and pericytes through the overgeneration of intracellular ROS, and thus be involved in the development of diabetic retinopathy [12].
• These data are compatible with the hypothesis that altered inositol phospholipid metabolism accounts for the loss of pericytes in diabetic retinopathy [13].
• The gentamicin produced retinal whitening with a cherry-red spot, generalized vascular incompetence, diffuse retinal necrosis, thrombosis of the large retinal blood vessels, widespread loss of the retinal capillary pericytes and endothelial cells, and a rapid extinction of the electroretinogram [14].
• METHODS: Endothelial cell and pericyte area were assessed by quantitative immunocytochemistry for CD34 and alpha-smooth muscle actin respectively, taking into consideration the dynamics of lutein cell hypertrophy and atrophy throughout the cycle and after HCG treatment [15].

Biological context of Pericytes

• Antibodies to transforming growth factor-beta 1 (TGF-beta 1) abrogate the inhibition of BAE cell movement by pericytes or SMCs [16].
• Similar kinetic parameters were obtained for factor X hydrolysis by tissue factor-factor VIIa on unperturbed pericytes and phosphatidylcholine vesicles [17].
• Elevated levels of RGS-5 in pericytes are also observed during wound healing and ovulation indicating a strong correlation between RGS-5 expression and active vessel remodeling beyond tumor angiogenesis [2].
• Taken together, the data demonstrate that in neuroblastoma, stromally derived MMP-9 contributes to angiogenesis by promoting blood vessel morphogenesis and pericyte recruitment [18].
• Radioreceptor studies that used [125I]ET-1 showed that pericytes contained high-affinity binding sites with Kd of 3 x 10(-10) M, and these binding affinities were unaffected by glucose concentration [19].

Anatomical context of Pericytes

• Pre-treatment of two types of human vascular pericytes, liver fat-storing cells or glomerular mesangial cells, with IFN-gamma dramatically enhanced DNA synthesis in response to PDGF or EGF [20].
• Simultaneous localization of beta actin with the entire F-actin pool was performed on microvascular pericytes or endothelial cells and 3T3 fibroblasts recovering from injury using anti-beta actin IgG in combination with fluorescent phalloidin [21].
• We show that pericytes of true capillaries (midcapillaries) apparently lack the smooth muscle isoform of alpha-actin whereas transitional pericytes of pre- and postcapillary microvascular segments do express this isoform [22].
• Results of these experiments revealed that pericyte beta actin is localized beneath the plasma membrane in association with filopods, pseudopods, and fan lamellae [21].
• Here, we show that after ischemic challenge, eNOS knockout mice [eNOS (-/-)] have defects in arteriogenesis and functional blood flow reserve after muscle stimulation and pericyte recruitment, but no impairment in endothelial progenitor cell recruitment [1].

Associations of Pericytes with chemical compounds

• These results and our previous findings concerning the presence of a cyclic GMP-dependent protein kinase (Joyce, N., P. DeCamilli, and J. Boyles, 1984, Microvasc. Res. 28:206-219) in pericytes demonstrate that these cells contain significant amounts of at least two proteins important for contraction regulation [23].
• Identification of multiple genes in bovine retinal pericytes altered by exposure to elevated levels of glucose by using mRNA differential display [24].
• Blood-borne WGA-HRP labeled the entire cerebrovascular tree from the luminal side 5 min after injection; pericytes, located on the abluminal surface of cerebral endothelia, sequestered the lectin conjugate 6 hr later [25].
• STI571 treatment also decreased pericyte coverage on tumor-associated endothelial cells [26].
• The numbers of both endothelial cells and pericytes increased significantly under hypoxic conditions; the O2 concentrations that achieved maximal growth promotion were 10% for endothelial cells and 2.5% for pericytes [27].

Gene context of Pericytes

• This is functionally important as administration of an antiangiogenic TSP-1 peptide (ABT-526) markedly inhibited growth of VEGF(-/-) tumors, with some ingress of pericytes [28].
• Ang1 mediates vessel maturation and integrity by the recruitment of pericytes [29].
• Conversely, intraocular injection of VEGF accelerated pericyte coverage of the preformed endothelial plexus, thereby revealing a novel function of this pleiotropic angiogenic growth factor [30].
• Heterozygous angiopoietin-2 deficiency completely prevented diabetes-induced pericyte loss and reduced the number of acellular capillary segments [31].
• Our results show that SDF-1 protein and mRNA are normally expressed by endothelial cells, pericytes, and either resident or explanted CD1a+ dendritic cells [32].

Analytical, diagnostic and therapeutic context of Pericytes

• In the tissue sections, indirect immunofluorescence revealed intense labeling of vascular smooth muscle cells and precapillary pericytes for SM alpha-actin [33].
• The influence of elevated glucose concentration on resting membrane voltage, electrogenic Na(+)-K(+)-ATPase, and ATP-sensitive potassium channels (KATP channels) was studied in cultured bovine retinal capillary pericytes using conventional microelectrodes [34].
• To test the hypothesis that differentiation of mesenchymal cells to pericytes/smooth muscle cells (SMC) is accompanied by VEGF expression, we used endothelial cell (EC) and mesenchymal cell cocultures to model cell-cell interactions that occur during vessel development [35].
• METHODS: Pericyte and SMC differentiation was characterized by immunohistochemistry with antibodies to NG2, desmin, alpha-smooth muscle actin (SMA), calponin, and caldesmon [36].
• RT-PCR confirmed that mRNAs corresponding to the receptors for PGD2, -E2, -F(2alpha), and -I(2) were expressed in human retinal pericytes [37].

References