Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years more than 150 cases of glomerulonephritis characterized by deposits of irregularly arranged fibrils have been documented. In the majority of these cases immunoglobulins and complement are the prime constituents of these deposits. We recently made a diagnosis of fibrillary glomerulonephritis without immunoglobulin deposition in two members of a family, a father and a son. In the father, proteinuria was first discovered 18 years ago. In 1985 he was referred to our outpatient clinic because of hypertension and increasing proteinuria. From that time onward he was regularly seen for blood pressure control. Nephrotic-range proteinuria persisted, without hardly any evidence of deterioration of renal function. Renal biopsies were performed in 1985 and 1993. His son underwent a renal biopsy in 1993 because of moderate proteinuria. The biopsies of both patients disclosed a distinct form of fibrillary glomerulonephritis that was characterized by massive deposits of a homogeneous, eosinophilic material in the mesangial and subendothelial areas. Staining for amyloid was negative. Immunofluorescence revealed that the biopsy specimens only stained faintly for immunoglobulins, complement factors C1q and C3, the extracellular matrix proteins, collagen IV, and laminin. However, they strongly stained for fibronectin. Using monoclonal antibodies specific for cell-derived fibronectin (IST-9) and plasma- and cell-derived fibronectin (IST-4), in the biopsy of the son we demonstrated that the fibronectin deposited in the glomeruli was mainly derived from the plasma, and to a lesser extent from resident glomerular cells. In addition, a moderate staining for amyloid P and vitronectin also was present. No or minor enhanced staining for collagen I, III, or V, heparan sulfate proteoglycan or its glycosaminoglycan side chains, tenascin, or thrombospondin could be observed. By electron microscopy the deposits in the mesangium and the subendothelial spaces appeared focally to be composed of irregularly arranged fibrils or microtubules 10 to 12 nm in diameter. Fibrillary glomerulonephritis with massive deposits of fibronectin represents a rare form of familial glomerulonephritis. In our patients the glomerulonephritis has an indolent course with hardly any deterioration of renal function.
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PMID:Familial glomerulonephritis characterized by massive deposits of fibronectin. 774 33

Fibrosis makes an important contribution to the pathophysiological events leading to the development of heart failure in ischemic and hypertensive heart disease. Since cardiac fibroblasts are mainly responsible for the synthesis and deposition of the extracellular matrix, we have established a method for isolating and cultivating human cardiac fibroblasts from explanted human hearts. The cell yield was 2.14+/-0.25x10(6 )cells in five independent isolations and the cell purity was 95-97%, contaminating cells being vascular smooth muscle cells and pericytes. Cultured cells were studied with respect to growth properties, morphology and deposition of components of the extracellular matrix. Isolated cells displayed a differentiated phenotype, including the second passage in culture; they synthesised collagen I, III, IV, fibronectin, vitronectin, tenascin and chondroitin sulphate and expressed an atypical angiotensin receptor. This atypical angiotensin receptor internalised angiotensins II and III but not angiotensin IV in a time-dependent manner. Stimulation of the cells with angiotensins II and III but not with angiotensin IV resulted in a dose-dependent stimulation of DNA synthesis. Co-incubation with the subtype-specific receptor antagonists Losartan and PD 123317 did not prevent the stimulation of DNA synthesis. The further characterisation of this receptor should provide insights into the pathobiochemical events leading to heart failure in hypertension and ischemic heart disease.
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PMID:Isolation and characterisation of human cardiac fibroblasts from explanted adult hearts. 878 Dec 21

This study was to assess the role of different components of the extracellular matrix (ECM) on the mobilization of Cai++ induced by angiotensin II in vascular smooth muscle cells (VSMC) from hypertensive (SHR) and normotensive (WKY) rats. The effect of AII (10-6 M) on Cai++ release was studied in VSMC isolated from the aorta of 5-week-old WKY and SHR using fluorescent imaging microscopy (fura-2). Cai++ mobilization was characterized by amplitude, slope of Cai++ increase and total amount of Cai++. Cells were cultured on glass coverslips (control) or coated with either collagen I, collagen IV, vitronectin, fibronectin and extracellular matrix (ECM) and studied at confluence between passage 3 and 9. A significant increase of Cai++ released by AII has been observed with cells from WKY cultured on collagen I (meam +/- SEM, amplitude: 192 +/- 12% of control values, slope: 194 +/- 13%, total amount Cai++: 173 +/- 12%, n = 270, p < or = 0.0001 for each, unpaired t-test). Conversely, response with SHR was not significatively modified. Cai++ mobilization was not significatively modified after culture of VSMC from SHR and WKY on collagen IV. A significative decrease of the slope (WKY: 66 +/- 6%, p < or = 0.0001; SHR: 83 +/- 5%, p < or = 0.03) and of the amount of Cai++ (WKY: 74 +/- 7%, p < or = 0.01; SHR: 74 +/- 5%, p < or = 0.01) has been observed after culture of VSMC from the 2 strains on vitronectin. A decrease in amplitude (53 +/- 3%, p < or = 0.0001), slope (38 +/- 4%, p < or = 0.0001) and Cai++ release (69 +/- 5%, p < or = 0.004, n = 106) has been observed in VSMC from SHR seeded on fibronectin. Conversely, in VSMC from WKY, Cai++ mobilisation has not been modified compared with control cells. Culture of VSMC from SHR on ECM induced a significative decrease of amplitude (49 +/- 2%), slope (54 +/- 4%) and Cai++ release (53 +/- 3%, p < or = 0.0001 for each, n = 122), while in WKY, ECM induced a significative stimulation of these parameters (amplitude: 157 +/- 11%, slope: 149 +/- 13% and Cai++ release: 130 +/- 9%, p < or = 0.0001 for each, n = 247). These results show that the Cai++ mobilization induced by AII is modified by the adhesion of cells to different ECM components. This suggests a modulation of the A II-associated signalling events via the focal adhesion points. Furthermore, a difference in this modulation is observed between SHR and WKY when cells are seeded on collagen I, fibronectin or ECM. These modulations of Cai++ mobilization could play a role in the regulation of growth and differentiation of cells during the development of hypertension.
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PMID:[Cellular adhesion to elements of the extracellular matrix in the hypertensive rat modulates the effect of angiotensin II]. 1048 64

Loss of membrane complement regulators accompanied by complement activation is suggested to be involved in the pathophysiological processes leading to tissue damage in myocardial ischaemia. In the present study we have investigated whether the same phenomenon may occur in ischaemic and/or venous hypertension leg ulcers. The deposition of complement, plasma complement regulators and expression of membrane regulators were detected by immunohistochemical methods, including immunofluorescence with antibodies against C3d, the terminal complement complex (TCC), vitronectin, clusterin, decay-accelerating factor (CD55) and protectin (CD59). Eleven frozen biopsies from ischaemic leg ulcers, 10 biopsies from venous hypertension leg ulcers, and 10 biopsies from normal skin were studied. In 9 of 11 ischaemic and in 5 of 10 venous hypertension leg ulcers, marked staining for TCC was found around the capillaries, most often at the ulcer margin. No TCC staining was found in normal skin. Staining for TCC was always accompanied by staining for clusterin and vitronectin and C3d. In normal skin, CD59 was found on the elastic fibers in the dermis, on the muscle coat, the Schwann sheath and acinar cells. Semiquantitative measurement of CD59 showed marked increased staining intensity in the endothelium in venous hypertension ulcers and diminished intensity in ischaemic ulcers compared to normal skin. No such difference could be observed for CD55. When TCC was positive in the capillary walls, weak or no staining for CD59 was found. A significantly higher ratio of TCC/CD59 was found in the ischaemic compared to venous ulcers (p = 0.018). This was due to a marked difference between the ulcer margins (p = 0.013). Localized areas in the venous ulcers had the same pattern as that seen in the ischaemic ulcers. Our results suggest that loss of CD59 may enhance deposition of TCC and that complement-dependent inflammation may be an important factor in the tissue-damaging processes seen in chronic leg ulcers.
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PMID:The terminal complement complex is generated in chronic leg ulcers in the absence of protectin (CD59). 1059 71

We recently demonstrated that alpha(v)beta(3) integrins are involved in the mechanisms of angiotensin II (Ang II)-induced DNA synthesis and collagen gel contractions in rat cardiac fibroblasts (CFBs), cellular mechanisms that are relevant for cardiac remodeling. The aim of the present study was to elucidate the effect of Ang II and other growth factors on the regulation of the alpha(v)beta(3) integrins in fibroblasts from neonatal rat hearts. The alpha(v)beta(3) integrin receptor expression was significantly increased (P<0.05) at the mRNA level after treatment with Ang II, transforming growth factor-beta(1) (TGF-beta(1)), and platelet-derived growth factor (PDGF) for 8 and 16 hours. The surface expression of the alpha(v) and beta(3) integrin subunits was elevated after 32 and 48 hours (P<0.05) as determined with flow cytometry. To investigate fibroblast motility, we performed chemotaxis experiments with transwell chambers. Ang II was chemotactic for CFBs, as tested with checkerboard experiments. The chemotactic effect was concentration dependent and was completely blocked by Ang II type 1 receptor blockers but not by Ang II type 2 receptor blocker PD 123319. Ang II- and PDGF-BB-mediated chemotaxis could be significantly inhibited by RGD peptides and the blocking antibodies against alpha(v)beta(3) integrin (both P<0.01). Adhesion of CFBs to vitronectin was partially inhibited by an antibody to alpha(v)beta(3) integrin but was mainly mediated by an alpha(v)beta(5) integrin. Relevant in vivo expression of alpha(v)beta(3) integrin by CFBs was confirmed with in situ hybridization with probes for alpha(v) and beta(3) mRNA in rat hearts. The present study demonstrates that the expression of alpha(v)beta(3) integrin is augmented by Ang II, PDGF, and TGF-beta(1) in neonatal CFBs. Furthermore, this integrin is involved in the chemotaxis, motility, and adhesion of CFBs. The present findings support the current concept that integrins participate in the control of fibroblast behavior during cardiac remodeling mechanisms.
Hypertension 2000 Apr
PMID:Angiotensin II and alpha(v)beta(3) integrin expression in rat neonatal cardiac fibroblasts. 1077 72

Both integrins and endothelins (ETs) are known to play important roles in vascular remodeling via proliferation, apoptosis, and migration of vascular smooth muscle cells (VSMCs), whose dysfunctions have been implicated in the pathogenesis of end-organ damage associated with hypertension and arteriosclerosis. However, whether there is any interaction between endothelin-1 (ET-1) and integrins remains unknown. Therefore, the aim of the present study was to elucidate whether ET-1 regulates the expression of integrin alpha(v) in rat VSMCs. ET-1 dose- and time-dependently suppressed the integrin alpha(v) messenger RNA (mRNA) transcripts, as quantified by a real-time quantitative polymerase chain reaction (PCR) method, and decreased the transcriptional activity of integrin alpha(v) gene, as demonstrated by integrin alpha(v)-luciferase assay. The inhibitory effect of ET-1 on integrin alpha(v) gene expression was abrogated by an ETA receptor antagonist (BQ123) but not by an ET(B) receptor antagonist (BQ788). ET-1 also suppressed the cell surface expression of integrin alpha(v)beta5 and the adhesion to vitronectin, but not to fibronectin. These results demonstrate that the adhesion of vitronectin to rat VSMCs is inhibited by ET-1 via the ET(A) receptors by suppressing integrin alpha(v) gene transcription, suggesting that ET-1 is involved in regulation of vascular integrin alpha(v) gene expression.
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PMID:Suppression of integrin alpha(v) expression by endothelin-1 in vascular smooth muscle cells. 1113 Dec 77

The interaction of the vascular smooth muscle cells (VSMCs) with the components of the matrix determines several functions of the cell, such as growth and differentiation. In contrast, an alteration in angiotensin (Ang) II-induced Ca(2+) mechanisms in VSMCs was reported in genetic hypertension. In this study, we wished to assess the effect of different components of the extracellular matrix on the increase of [Ca(2+)](i) induced by Ang II in VSMCs from spontaneously hypertensive rats (SHR) compared with those from normotensive Wistar-Kyoto rats (WKY). Results demonstrate for the first time that elements of the extracellular matrix modulate the Ang II-induced Ca(2+) transport mechanisms. This modulation is different in cells from WKY compared with those from SHR. Thus, growing cells from SHR on collagen I, collagen IV, fibronectin, vitronectin, or Matrigel induced a significant decrease in Ang II-induced Ca(2+) release from internal stores, whereas in cells from WKY, no effect could be observed except for those grown on collagen I, which increased Ca(2+) release. Fibronectin and vitronectin, however, induced a decrease in Ang II-induced Ca(2+) influx in WKY, whereas no effect could be observed in SHR. Conversely, collagen I and collagen IV induced an increase in this influx in SHR but not in WKY, whereas Matrigel increased the influx in both strains. These results suggest a modulation of the Ang II-associated signaling events by the matrix elements via the focal adhesion points. The understanding of these synergies should provide insight into issues such as development of hypertrophy of large vessels in hypertension.
Hypertension 2001 Jun
PMID:Effect of extracellular matrix elements on angiotensin II-induced calcium release in vascular smooth muscle cells from normotensive and hypertensive rats. 1140 96

Angiotensin II (Ang II) is involved in hypertension-related arterial wall hypertrophy [1]. Regulation of AT II transduction pathway in vascular smooth muscle cells (VSMC) may involve cytoskeleton and extracellular matrix (ECM) [2]. We assessed the role of components of ECM on Cai2+ increase induced by Ang II in Wistar-Kyoto (WKY) and Spontaneously Hypertensive Rats (SHR) aortic VSMC. The effect of Ang II (1 mumol) on Ca2+ mobilization was studied in cultured VSMC isolated from the aorta of 6-wk old WKY (MAP (m +/- SE) = 98 +/- 4 mmHg) and SHR (136 +/- 5 mmHg; p < 0.05), using fluorescent imaging microscopy (Fura-2 AM). Cai2+ release from internal stores and Ca2+ influx were assessed in the absence and upon reintroduction of external Ca2+ respectively. Cells were cultured on uncoated glass coverslips (control) or coated with either collagen I (10 micrograms/mL), collagen IV (7 micrograms/mL), vitronectin (0.1 microgram/mL), fibronectin (3 micrograms/mL) and extracellular matrix extract (matrigel, 1/10) and studied at confluence. Paxillin was located in cells by indirect immunofluorescence micrography. Results are expressed in % of Control. Statistical significance (p < 0.05) was assessed with Student's t-test for unpaired data. The effects on Ang II-induced Ca2+ mobilization of growing cells on ECM are in Table. Paxillin in Control cells appeared as dots at the cell boundaries. Density increased in cells grown on collagen I with a diffuse distribution in the WKY cells. On matrigel, paxillin was located in a belt-like fashion at the periphery of the cell. These effects were not linked to differences in cell cycle (flux cytometry).
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PMID:[Role of extracellular matrix in angiotensin II signalling in aortic smooth muscle cells: relationship with arterial hypertension]. 1236 72

Hantaviruses cause two diseases of man, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Pathogenic and non-pathogenic hantaviruses use beta3 and beta1 integrins, respectively, to enter endothelial cells. Beta3 integrins were recently reported to bind receptors that regulate vascular permeability suggesting that hantavirus beta3 integrin interactions may regulate endothelial cell function and contribute to viral pathogenesis. In this study we investigated the ability of pathogenic and non-pathogenic hantaviruses to regulate beta3 and beta1 integrin directed endothelial cell functions. We found that pathogenic NY-1, SNV, HTN, SEO and PUU viruses blocked endothelial cell migration on beta3, but not beta1, integrin ligands. Migration is similarly inhibited by antibodies to beta3 integrins which selectively block vitronectin directed endothelial cell migration. As a result, the ability of endothelial cells to migrate on integrin ligands was selectively inhibited by only pathogenic hantaviruses. Infection by NY-1 virus inhibited endothelial cell migration as early as 24-48 h post-infection. In contrast, non-pathogenic PH and TUL viruses had no effect on the ability of endothelial cells to migrate on either beta3 or beta1 integrin ligands from 1 to 5 days post-infection. These findings indicate that only hantaviruses which use beta3 integrins, and are associated with HPS and HFRS diseases, functionally dysregulate endothelial cell migration. These findings further demonstrate that hantaviruses regulate only beta3 integrin directed endothelial cell functions and have no effect on beta1 integrin functions. Since beta3 integrins are linked to changes in vascular permeability and the maintenance of vascular integrity, these findings suggest a means by which hantavirus usage and regulation of beta3 integrins may contribute to hantavirus pathogenesis.
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PMID:Pathogenic hantaviruses selectively inhibit beta3 integrin directed endothelial cell migration. 1237 53

Benidipine is a dihydropyridine-Ca2+ channel blocker used in the treatment of hypertension and angina pectoris. In the present study, we examined the effects of benidipine on the endothelial differentiation of circulating endothelial progenitor cells (EPCs) using an in vitro culture method. Peripheral blood derived mononuclear cells (PBMCs) containing EPCs were isolated from C57BL/6 mice, and then the cells were cultured on vitronectin/gelatin-coated slide glasses. After 7 days of culture, endothelial cells differentiated from EPCs were identified as adherent cells with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine-labeled acetylated low density lipoprotein (Dil-Ac-LDL) uptake and lectin binding under a fluorescent microscope. Incubation of PBMCs for 7 days with benidipine (0.01-1 micromol/l) significantly increased the number of Dil-Ac-LDL+/fluorescein isothiocyanate-lectin (FITC-Lectin)+ cells. Wortmannin, a phosphoinositide-3 kinase (PI3K) inhibitor, selectively attenuated the effect of benidipine on the endothelial differentiation. In addition, benidipine treatment augmented the phosphorylation of Akt, indicating that the PI3K/Akt pathway contributed, at least in part, to the endothelial differentiation induced by benidipine. These results suggest that the treatment with benidipine may increase the endothelial differentiation of circulating EPCs and contribute to endothelial protection, prevention of cardiovascular disease, and/or an improvement of the prognosis after ischemic damage.
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PMID:Benidipine, a dihydropyridine-Ca2+ channel blocker, increases the endothelial differentiation of endothelial progenitor cells in vitro. 1737 77


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