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M C Cid

Publications and source records attributed to M C Cid.

At least 19 recordsLinked to original sources
PubMed2001

Small-vessel vasculitis surrounding a spared temporal artery: clinical and pathological findings in a series of twenty-eight patients.

OBJECTIVE: Occasionally, a temporal artery biopsy reveals small-vessel vasculitis (SVV) surrounding a spared temporal artery, the significance of which is unclear. We analyzed the final diagnosis in a series of patients with this condition and tried to identify histopathologic features with potential usefulness in predicting the ultimate diagnosis. METHODS: We performed a clinical and histopathologic review of 28 patients in whom SVV surrounding a spared temporal artery was the first histologic finding that led to the diagnosis of vasculitis. For comparison purposes, we analyzed the pattern of small vessel involvement in 30 patients with biopsy-proven giant cell arteritis (GCA). RESULTS: GCA was considered the most likely diagnosis in 12 patients, based on the absence of clinical evidence of additional organ involvement and normal findings on muscle biopsy and electrophysiologic study. Three patients had systemic necrotizing vasculitis (SNV), based on the demonstration of typical lesions on subsequent muscle, nerve, or kidney biopsy. After extensive evaluation, 4 patients remained unclassifiable. Nine patients were incompletely studied. Fibrinoid necrosis was significantly more frequent in patients with SNV (P = 0.0022), whereas involvement of vasa vasorum was more frequent in patients classified as having GCA (P = 0.022). No differences in the pattern of small vessel involvement were found in patients with SVV surrounding a spared temporal artery who were classified as having GCA compared with patients with biopsy-proven GCA. Granulocytes were observed at similar frequency in all conditions. CONCLUSION: SVV may be the only abnormal feature in a temporal artery biopsy and the only histologic evidence of vasculitis. The diagnosis of GCA can be reasonably established in most of these patients when there is no apparent evidence of additional organ involvement. However, when fibrinoid necrosis is observed or the temporal artery vasa vasorum are not involved, SNV must be extensively excluded.

Adult↗
PubMed2001

Tissue targeting and disease patterns in systemic vasculitis.

The systemic vasculitides include a group of diseases with highly heterogeneous organ distribution and disease expression patterns. The mechanisms mediating tissue targeting in systemic vasculitis are largely unknown. Mechanical forces may contribute to the distribution of lesions in immune complex-mediated vasculitis. The site at which the antigen is encountered may be crucial in determining the location of inflammatory infiltrates in some vasculitides. Co-existence of different immunopathogenic mechanisms with variable dominance may generate diversity in disease presentation patterns. Heterogeneous and incompletely understood triggering mechanisms attract inflammatory cells to the site of interest through sophisticated molecular mechanisms: interplay between leukocyte receptors and endothelial ligands, and interactions between chemokines and chemokine receptors. Even with a similar distribution of lesions, patients with vasculitis may display highly variable clinical manifestations. Variations in genes involved in immune response might determine the severity of disease, the intensity of the systemic inflammatory response, the degree of vessel occlusion and the response to therapy.

Adult↗
PubMed2000

Cell adhesion molecules in the development of inflammatory infiltrates in giant cell arteritis: inflammation-induced angiogenesis as the preferential site of leukocyte-endothelial cell interactions.

OBJECTIVE: To investigate the expression pattern of adhesion molecules involved in leukocyte-endothelial cell interactions in giant cell arteritis (GCA). METHODS: Immunohistochemical analysis was performed on frozen temporal artery sections from 32 patients with biopsy-proven GCA and from 12 control patients with other diseases. Adhesion molecules identified were intercellular adhesion molecule 1 (ICAM-1), ICAM-2, ICAM-3, vascular cell adhesion molecule 1 (VCAM-1), platelet endothelial cell adhesion molecule 1 (PECAM-1), E-selectin, P-selectin, L-selectin, lymphocyte function-associated antigen 1 (LFA-1), very late activation antigen 4 (VLA-4), Mac-1 (CD18/CD11b), and gp 150,95 (CD18/CD11c). Clinical and biochemical parameters of inflammation in the patients, as well as the duration of previous corticosteroid treatment, were prospectively recorded. RESULTS: Constitutive (PECAM-1, ICAM-1, ICAM-2, and P-selectin) and inducible (E-selectin and VCAM-1) endothelial adhesion molecules for leukocytes were mainly expressed by adventitial microvessels and neovessels within inflammatory infiltrates. Concurrent analysis of leukocyte receptors indicated a preferential use of VLA-4/VCAM-1 and LFA-1/ICAM-1 at the adventitia and Mac-1/ICAM-1 at the intima-media junction. The intensity of inducible endothelial adhesion molecule expression (E-selectin and VCAM-1) correlated with the intensity of the systemic inflammatory response. Previous corticosteroid treatment reduced, but did not completely abrogate, the expression of the inducible endothelial adhesion molecules E-selectin and VCAM-1. CONCLUSION: Inflammation-induced angiogenesis is the main site of leukocyte-endothelial cell interactions leading to the development of inflammatory infiltrates in GCA. The distribution of leukocyte-endothelial cell ligand pairs suggests a heterogeneity in leukocyte-endothelial cell interactions used by different functional cell subsets at distinct areas of the temporal artery.

Adrenal Cortex Hormones↗
PubMed1999

Fibronectin upregulates gelatinase B (MMP-9) and induces coordinated expression of gelatinase A (MMP-2) and its activator MT1-MMP (MMP-14) by human T lymphocyte cell lines. A process repressed through RAS/MAP kinase signaling pathways.

T-lymphocyte migration into tissues requires focal degradation of the basement membrane. In this study, we show that transient adherence to fibronectin induces the production of activated forms of matrix metalloproteinase-2 (MMP-2) and MMP-9, as well as downregulation of tissue inhibitor of metalloproteinase-2 (TIMP-2) by T-cell lines. MMP-2 activation was likely achieved by inducing a coordinated expression of membrane-type matrix metalloproteinase-1 (MMP-14), a major activator of MMP-2. Blocking monoclonal antibodies against alpha4, alpha5, and alphav integrins strongly reduced MMP-2 and MMP-9 production induced by fibronectin. Disrupting actin cytoskeleton organization by cytochalasin D strongly enhanced fibronectin-induced MMP-2 and MMP-9 expression. Inhibiting Src tyrosine kinases with herbimycin A reduced MMP-2 and MMP-9 production with no effect on cell attachment. By contrast, G-protein inhibition by pertussis toxin, or transfection with a dominant negative mutant of Ha-Ras strongly increased fibronectin-induced MMP-2 and MMP-9. Inhibition of PI3 kinase, MAPkinase (MEK1), or p38 MAPkinase by wortmannin, PD 98059, or SB 202190, respectively, strongly promoted fibronectin-induced MMP2 and MMP-9. Cells at high density lost their ability to synthesize MMP-2 and MMP-9 in response to fibronectin and MMP expression was restored by transfection with a dominant-negative mutant of Ha-Ras or by treatment with wortmannin, PD 98059, or SB 202190. Our findings suggest that adhesion to fibronectin transduces both stimulatory (through Src-type tyrosin kinases) and inhibitory signals (through Ras/MAPKinase signaling pathways) for MMP-2 and MMP-9 expression by T lymphocytes and that their relative predominance is regulated by additional stimuli related to cell adhesion, motility, and growth.

Androstadienes↗
PubMed1999

Interferon-alpha may exacerbate cryoblobulinemia-related ischemic manifestations: an adverse effect potentially related to its anti-angiogenic activity.

The discovery of the strong association between hepatitis C virus (HCV) infection and the development of mixed cryoglobulinemia has motivated active testing of antiviral-directed alternative therapies. Several trials have demonstrated that classic cryoglobulinemia-associated manifestations improve with interferon-alpha (IFNalpha) treatment. Herein we report on 3 HCV-infected patients with severe cryoglobulinemia-related ischemic manifestations who were closely followed up during IFNalpha therapy. Clinical evaluations with special attention to ischemic lesions, liver function tests, and cryocrit determinations were serially performed. In addition to prednisone and immunosuppressive agents, the patients received IFNalpha at 3 x 10(6) units, 3 times per week for 2 months, 3 months, and 4 months, respectively. In all 3 patients, systemic features improved, liver function results returned to normal, and cryocrit values decreased. However, ischemic lesions became less vascularized and ischemia progressed, leading to transmetatarsal and subcondylar amputation, respectively, in 2 of the patients and fingertip necrosis and ulcer enlargement in the third. Skin biopsies performed before IFNalpha therapy and after 2 months of IFNalpha therapy in the third patient showed a significant decrease in subepidermal microvessels. When IFNalpha was discontinued, the lesions finally healed. Cryoglobulinemia-related ischemic lesions may worsen during IFNalpha treatment, presumably through a decrease in inflammation-induced angiogenesis. The anti-angiogenic activity of IFNalpha may delay the appropriate healing of ischemic lesions.

Cryoglobulinemia↗
PubMed1999

Circulating soluble adhesion molecules in patients with giant cell arteritis. Correlation between soluble intercellular adhesion molecule-1 (sICAM-1) concentrations and disease activity.

OBJECTIVE: To evaluate whether changes in concentrations of circulating adhesion molecules are related to disease activity in patients with giant cell arteritis (GCA). METHODS: A sandwich ELISA was used to measure soluble intercellular adhesion molecule-1 (sICAM-1), sICAM-3, vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), and L-selectin (sL-selectin) in serum and plasma samples from patients with GCA. A cross sectional study was performed on 64 GCA patients at different activity stages and on 35 age and sex matched healthy donors. Thirteen of these patients were evaluated at the time of diagnosis and serially during follow up. RESULTS: At the time of diagnosis, sICAM-1 concentrations were significantly higher in active GCA patients than in controls (mean (SD) 360.55 (129.78) ng/ml versus 243.25 (47.43) ng/ml, p < 0.001). In contrast, sICAM-3, sVCAM-1, sE-selectin, and sL-selectin values did not differ from those obtained in normal donors. With corticosteroid administration, a decrease in sICAM-1 concentrations was observed, reaching normal values when clinical remission was achieved (263.18 (92.7) ng/ml globally, 293.59 (108.39) ng/ml in the group of patients in recent remission, and 236.83 (70.02) ng/ml in those in long term remission). In the 13 patients followed up longitudinally, sICAM-1 values also normalised with clinical remission (225.87 (64.25) ng/ml in patients in recent remission, and 256.29 (75.15) ng/ml in those in long term remission). CONCLUSIONS: Circulating sICAM-1 concentrations clearly correlate with clinically apparent disease activity in GCA patients. Differences with results previously found in patients with other vasculitides may indicate that different pathogenic mechanisms contribute to vascular inflammation in different disorders.

Aged↗
PubMed1999

Expression of beta-integrin adhesion molecules in non-Hodgkin's lymphoma: correlation with clinical and evolutive features.

PURPOSE: To analyze beta-integrin expression in non-Hodgkin's lymphomas (NHLs) in order to assess its distribution among histologic subtypes and correlate with clinical features and outcome. PATIENTS AND METHODS: The expression of alpha2 through alpha6 and beta1 common chains of very late activation antigen (VLA ) molecules and alphaL (CD11a) and beta2 common (CD18) chains of leukocyte function-associated antigen 1 molecule were studied in 137 patients with NHL. Immunostaining was performed by a streptavidin-biotin alkaline phosphatase method, and integrin expression was semiquantitatively assessed. Correlation with clinical features was analyzed in 80 patients consecutively diagnosed as having immunocytoma (five cases), follicular lymphoma (19 cases), mantle-cell lymphoma (MCL; four cases), diffuse large-cell lymphoma (DLCL; 40 cases), lymphoblastic lymphoma (LL; six cases), anaplastic Ki-1-positive lymphoma (one case), and other peripheral T-cell lymphoma (five cases). RESULTS: MCL cells did not show alpha2 and alpha6 expression, whereas most expressed weak to moderate levels of alpha3, alpha4, and alpha5. LL mostly showed alpha2 to alpha5 expression, whereas alpha6 was observed in seven of 11 cases (higher proportion than that shown in other subgroups). Alpha chains of VLA molecules were present more frequently in T-cell than in B-cell lymphomas. Patients with moderate/strong alpha4, CD11a, and beta2 common chain expression presented more frequently with advanced stage and bone marrow infiltration. Moderate/strong alpha4, alpha5, and beta1 common chain expression correlated with extranodal involvement. In the subset of B-cell DLCL patients, negative/weak expression of alpha3 and alpha4 chains was related to a higher complete response rate. Moreover, negative or weak expression of alpha2, alpha3, alpha4, and beta1( )common chain had favorable significance for overall and failure-free survivals. CONCLUSION: In NHL, beta-integrin expression is related to histologic subtype. The expression pattern of these molecules probably influences disease dissemination and patients' prognoses.

CD18 Antigens↗
PubMed1998

Association between strong inflammatory response and low risk of developing visual loss and other cranial ischemic complications in giant cell (temporal) arteritis.

OBJECTIVE: To identify clinical and biochemical parameters that have good predictive value for identifying giant cell (temporal) arteritis (GCA) patients who are at high or low risk of developing cranial ischemic events. METHODS: In this multicenter study, records of patients at 3 university hospitals in Barcelona were reviewed retrospectively. Two hundred consecutive patients with biopsy-proven GCA were studied. RESULTS: Thirty-two patients developed irreversible cranial ischemic complications. The duration of clinical symptoms before diagnosis was similar in patients with and those without ischemic events. Patients with ischemic complications less frequently had fever (18.8% versus 56.9%) and weight loss (21.9% versus 62%) and more frequently had amaurosis fugax (32.3% versus 6%) and transient diplopia (15.6% versus 3.6%). Patients with ischemic events had lower erythrocyte sedimentation rates (ESR) (82.7 mm/hour versus 104.4 mm/hour) and higher concentrations of hemoglobin (12.2 gm/dl versus 10.9 gm/dl) and albumin (37.4 gm/liter versus 32.7 gm/liter). Clinical inflammatory status and biologic inflammatory status were defined empirically (clinical: fever and weight loss; biologic: ESR > or =85 mm/hour and hemoglobin < 11.0 gm/dl). Patients not showing a clinical and biologic inflammatory response were at high risk of developing ischemic events (odds ratio [OR] 5, 95% confidence interval [95% CI] 2.05-12.2). The risk was greatly reduced among patients with either a clinical (OR 0.177, 95% CI 0.052-0.605) or a biologic (OR 0.226, 95% CI 0.076-0.675) inflammatory reaction. No patient with both a clinical and a biologic response developed ischemic events. CONCLUSION: The presence of a strong acute-phase response defines a subgroup of patients at very low risk of developing cranial ischemic complications. Our findings provide a rationale for testing less aggressive treatment schedules in these individuals. Conversely, a low inflammatory response and the presence of transient cranial ischemic events provide a high risk of developing irreversible ischemic complications and require a prompt therapeutic intervention.

Aged↗
PubMed1998

Dynamic pattern of endothelial cell adhesion molecule expression in muscle and perineural vessels from patients with classic polyarteritis nodosa.

OBJECTIVE: To investigate endothelial cell adhesion molecule expression in vessels from patients with classic polyarteritis nodosa (PAN). METHODS: Frozen sections of 21 muscle and 16 nerve samples from 30 patients with biopsy-proven PAN and 12 histologically normal muscle and 2 histologically normal nerve samples from 12 controls were studied immunohistochemically, using specific monoclonal antibodies (MAb) that recognize adhesion molecules. Adhesion molecules identified were intercellular adhesion molecule 1 (ICAM-1), ICAM-2, ICAM-3, vascular cell adhesion molecule 1 (VCAM-1), platelet endothelial cell adhesion molecule 1 (PECAM-1), E-selectin, P-selectin, L-selectin, lymphocyte function-associated antigen 1 (LFA-1), and very late activation antigen 4 (VLA-4). Neutrophils were identified with a MAb recognizing neutrophil elastase. Endothelial cells were identified with the lectin ulex europaeus. RESULTS: In early lesions, expression of PECAM-1, ICAM-1, ICAM-2, and P-selectin was similar to that in control samples, and VCAM-1 and E-selectin were induced in vascular endothelium. In advanced lesions, immunostaining for adhesion molecules diminished or disappeared in luminal endothelium, whereas these molecules were clearly expressed in microvessels within and surrounding inflamed vessels. Staining in endothelia from vessels in a healing stage tended to be negative. A high proportion of infiltrating leukocytes expressed LFA-1 and VLA-4, and only a minority expressed L-selectin. No relationship between the expression pattern of adhesion molecules and clinical features, disease duration, or previous corticosteroid treatment was observed. CONCLUSION: Endothelial adhesion molecule expression in PAN is a dynamic process that varies according to the histopathologic stage of the vascular lesions. The preferential expression of constitutive and inducible adhesion molecules in microvessels suggests that angiogenesis contributes to the persistence of inflammatory infiltration in PAN.

Adult↗
PubMed1998

Large vessel vasculitides.

During the past few years remarkable progress has been achieved in the understanding of the pathogenic mechanisms leading to vascular inflammation and injury in giant cell (temporal) arteritis. T lymphocytes are activated by specific recognition of a putative antigen residing in the arterial wall and, subsequently, activate macrophages that undergo a functional differentiation and contribute to vessel damage through various pathways. Vascular response to inflammation amplifies the inflammatory response through neovascularization and adhesion molecule expression. We are beginning to appreciate that products released by infiltrating inflammatory cells may play an important role in vessel occlusion and resulting ischemic complications. Concomitantly, synovitis underlying polymyalgia rheumatica musculoskeletal symptoms has been immunopathologically characterized and the nature of its relationship to giant cell arteritis is discussed. Although some components of the disease are highly corticosteroid responsive, other underlying pathogenic mechanisms may remain active. Long-term outcome is heterogeneous in patients with giant cell arteritis. Much less is known about the pathogenesis of Takayasu's arteritis. Recent work supports its association with HLA class I antigens, which may differ in different geographic areas or ethnic groups. Because Takayasu's disease expression may vary in different ethnic settings, this possibility has led to the proposal of new diagnostic criteria. Finally, the role of new imaging techniques in diagnosis and assessment of disease activity is discussed.

Angiography↗
PubMed1998

Expression of the adhesion molecule ICAM-1 in non-Hodgkin's lymphoma: relationship with tumor dissemination and prognostic importance.

PURPOSE: To study the expression of intercellular adhesion molecule-1 (ICAM-1) by non-Hodgkin's lymphomas and to assess its correlation with disease extension and prognosis. PATIENTS AND METHODS: ICAM-1 (CD54-IOL54) expression was studied in 70 patients (35 male/35 female; median age, 56 years) with non-Hodgkin's lymphoma from a single institution. Immunostaining was performed using a streptavidine-biotin alkaline phosphatase method and ICAM-1 expression was evaluated in a semiquantitative manner. The histologic distribution of the cases was the following: small lymphocytic, five cases; follicular, 14; mantle cell, five; diffuse large cell, 41; and T lymphoblastic, five. Forty patients (57%) were in stage IV, bulky disease was observed in 25 patients (36%), and extranodal involvement in 48 patients (69%). RESULTS: ICAM-1 expression was negative (-) in 14 patients (20%), weak (+) in 21 (30%), positive (++) in 30 (43%), and strongly positive ( ) in five (7%). No significant relationship was found between ICAM-1 expression and the lymphoma histologic subtype. Patients with negative or weak ICAM-1 expression had more frequently disseminated (stage IV) disease (74% v 40%; P = .007), extranodal involvement (86% v 51%; P = .004), and bone marrow infiltration (57% v 26%; P = .015) than the remainders. Positive ICAM-1 patients had survival rates significantly better than those in whom ICAM-1 was negative or weakly expressed [2-year overall survival: 77% v 50%, respectively; P < .025]. In a multivariate study, ICAM-1 (P = .005) maintained, along with histologic subtype (P = .001) and the international prognostic index (IPI) (P = .056), its importance for predicting survival. Finally, when the group of aggressive non-Hodgkin's lymphoma patients was analyzed, ICAM-1 expression inversely correlated with advanced stage (P = .025), extranodal involvement (P = .01), and bone marrow infiltration (P = .01), complete response (CR) achievement (65% v 32%; P = .025), and overall survival (70% v 26% at 2 years; P < .005). CONCLUSION: In lymphoma patients, ICAM-1 expression correlates with lymphoma dissemination and is useful to assess prognosis.

Adolescent↗
PubMed1997

T-cell population of primary and secondary cutaneous B-cell lymphomas does not express the cutaneous lymphocyte-associated antigen (CLA).

Primary cutaneous B-cell lymphomas (CBCL) are a group of malignant lymphomas with apparently distinct clinicopathological and immunophenotypical features. As in other B-cell lymphomas, the accompanying benign cell population in CBCL includes a variable number of T lymphocytes whose role is not well understood. In the present study we characterized the immunophenotype of these T cells and compared it with that of the reactive T-cell population in specific skin involvement by noncutaneous B-cell malignancies. Our results indicated that most T cells in both primary and secondary B-cell lymphomas were CLA+ memory/effector helper T cells which differed from the currently known CLA+ memory/effector helper T lymphocytes of the skin-associated lymphoid tissue (SALT) system. However, the endothelial CLA ligand, E-selectin, was expressed on dermal vessels. These results suggest that a B cell environment and/or a lack of epidermal involvement promote(s) the recruitment into the skin of a different, apparently less specific, subset of memory helper T cells from those seen in T-cell-mediated dermatoses.

Antigens, CD7↗
PubMed1997

Circulating soluble adhesion molecules in patients with classical polyarteritis nodosa.

The objective was to evaluate whether changes in circulating soluble adhesion molecule levels reflect disease activity in patients with systemic polyarteritis nodosa (PAN). A sandwich ELISA was used to measure soluble (s) intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), E-selectin, L-selectin and P-selectin in sera and plasma from 22 patients with active PAN, in sera from 13 of these patients taken serially during follow-up, and in sera from 13 healthy controls. At the time of diagnosis, sICAM-1, sVCAM-1 and sE-selectin levels (488.5 +/- 201.3, 1176.5 +/- 514.1 and 60.6 +/- 27 ng/ml, respectively) were significantly higher in patients than in controls (P < 0.0001, P = 0.001 and P = 0.003, respectively). In contrast, sL-selectin levels tended to be lower in patients than in controls. Within the first 7 days after starting treatment, there was a significant increase in sICAM-1 concentrations, which fell thereafter, but did not completely reach normal levels when patients achieved clinical remission. sE-selectin also remained elevated during follow-up. Only sVCAM-1 decreased, tending to reach normal values in inactive disease. Increased levels of sICAM-1, sVCAM-1 and sE-selectin, and decreased levels of sL-selectin, in active PAN suggest immune and endothelial stimulation during disease activity. Abnormal levels of soluble adhesion molecules in clinically inactive patients might reflect persistence of immune activation and/or endothelial cell exposure to a remaining inflammatory microenvironment.

Adult↗
PubMed1997

Clinical features in patients with permanent visual loss due to biopsy-proven giant cell arteritis.

The objective was to determine associated clinical findings in patients with visual loss due to giant cell arteritis (GCA) by means of a record review of 146 patients with biopsy-proven GCA. Twenty-three (15.75%) patients had lost vision. All of these patients complained of classical GCA cranial symptoms for an average of 1.3 months, 34.8% had an apparent isolated polymyalgia rheumatica for an average of 10.8 months and 65.2% had premonitory visual symptoms before visual loss for an average of 8.5 days. A clear delay in diagnosis and treatment was present in 15 patients (65.2%) who complained of at least two classical cranial symptoms for longer than 3 weeks and/or who had presented premonitory visual symptoms for longer than 72 h before blindness. Two additional patients lost vision while receiving standard steroid therapy. In conclusion, a high proportion of patients with permanent visual loss have a delayed diagnosis and treatment. A wider recognition of the disease would potentially reduce the prevalence of irreversible visual loss among GCA patients.

Biopsy↗
PubMed1996

Expression of an estrogen receptor by human coronary artery and umbilical vein endothelial cells.

BACKGROUND: Premenopausal women have much lower susceptibility to coronary artery disease than do men or postmenopausal women. It has been proposed that estrogen plays a role in cardioprotection, but little information is available regarding the mechanism by which estrogen may help to protect the vasculature. Here, we describe an estrogen receptor (ER) in human coronary artery and umbilical vein endothelial cells. METHODS AND RESULTS: Human umbilical vein endothelial cells and human coronary artery endothelial cells were cultured in hormone-free medium for 48 hours before experiments. Estradiol (3.7 nmol/L) added to cultures promoted proliferation by a mechanism that is inhibited by the specific ER antagonist ICI182,780. Estradiol-treated cells incorporated twice the [3H]thymidine of hormone-free cells; this increase was prevented by ICI182,780. Endothelial cells from both sources stained in a nuclear pattern with an ER-specific antibody. Ribonuclease protection assay detected mRNA for the ER. Ligand-binding studies estimated 2 x 10(4) to 8 x 10(4) receptors per cell and a Kd of approximately 5 nmol/L. Interaction of ERs with a consensus estrogen response element was shown by an electrophoretic mobility shift assay. In addition, an antibody against the ER supershifted the protein-DNA complex. CONCLUSIONS: These studies define the presence of an ER in human coronary artery and umbilical vein endothelial cells. They support the hypothesis that cardioprotective effects of estrogen are mediated, at least in part, through a classic steroid hormone receptor mechanism.

Arteries↗