Biomedical subjects

N Ferrara

Publications and source records attributed to N Ferrara.

At least 145 records · Page 8Linked to original sources

PubMed1994

Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR.

The recently identified placenta growth factor (PIGF) is a member of the vascular endothelial growth factor (VEGF) family of growth factors. PIGF displays a 53% identity with the platelet-derived growth factor-like region of VEGF. By alternative splicing of RNA, two PIGF isoforms are generated: PIGF131 (PIGF-1) and PIGF152 (PIGF-2). Relative to PIGF131, PIGF152 has a 21-amino acid insertion enriched in basic amino acids. Little is known at the present time about the significance and function of these proteins. To assess their potential role, we cloned the cDNAs coding for both isoforms, expressed them in mammalian cells, and purified to apparent homogeneity the recombinant proteins. Like VEGF, the PIGF isoforms are homodimeric glycoproteins. PIGF131 is a non-heparin binding protein, whereas PIGF152 strongly binds to heparin. We examined the ability of PIGF to bind to soluble VEGF receptors, Flt-1 and Flk-1/KDR, and characterized the binding of PIGF to endothelial cells. While the PIGF proteins bound with high affinity to Flt-1, they failed to bind to Flk-1/KDR. Binding of 125I-PIGF to human endothelial cells revealed two classes of sites, having high and low affinity. The high affinity site is consistent with Flt-1; the identity of the low affinity site remains to be determined. Purified PIGF isoforms had little or no direct mitogenic or permeability-enhancing activity. However, they were able to significantly potentiate the action of low concentrations of VEGF in vitro and, more strikingly, in vivo.

Adrenal Cortex↗

PubMed1994

Vascular endothelial growth factor. A cytokine modulating endothelial function in rheumatoid arthritis.

Angiogenesis is important in the proliferation of inflammatory synovial tissue. Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen that is also angiogenic in vivo. We examined the potential role of VEGF in mediating chemotaxis and proliferation of endothelial cells in rheumatoid arthritis (RA) using samples of synovial tissue and synovial fluid from 55 arthritic patients. Synovial fluid VEGF by ELISA was higher in RA synovial fluids (386 +/- 122 ng/ml) (SE) compared with osteoarthritis (OA) synovial fluids (< 0.8 ng/ml) (p < 0.05) or synovial fluids from patients with other arthritides (6.6 +/- 2 ng/ml). In addition to its known mitogenic properties, we found that human rVEGF was chemotactic for HUVECs at concentrations above 0.02 nM. Incubation of RA synovial fluids with neutralizing anti-VEGF resulted in 23 to 66% (mean 53 +/- 4%) inhibition of HUVEC chemotaxis. Conditioned medium from four of five RA synovial tissue explants was mitogenic for bovine adrenal capillary endothelial cells. Anti-VEGF neutralized from 19 to 42% (mean 28 +/- 4%) of this mitogenic activity. To determine the cellular source of VEGF in synovial tissue, we employed immunohistochemistry. VEGF+ cells were rarely (< 1%+) found in normal synovial tissues. In contrast, RA and OA synovial tissues exhibited VEGF+ lining cells (8% and 13%, respectively). A few synovial tissue macrophages were VEGF+ in both RA and OA (5% and 2%, respectively). These results elucidate a newly described function for VEGF as a potent chemotaxin for endothelial cells as well as a role for VEGF in RA-associated endothelial migration and proliferation.

Arthritis, Rheumatoid↗

PubMed1994

Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells.

Transforming growth factor beta (TGF-beta) is a multifunctional polypeptide that regulates the proliferation and differentiation of various cells and has an angiogenic effect in vivo, although it inhibits the growth of cultured endothelial cells. We report here that TGF-beta treatment of quiescent cultures of mouse embryo-derived AKR-2B cells, which are growth-stimulated by TGF-beta, and human lung adenocarcinoma A549 cells, which are growth-inhibited by TGF-beta, results in the induction of vascular endothelial growth factor (VEGF) mRNA and protein. Maximal VEGF mRNA levels occurred 4-8 h after stimulation with a decline to background levels in 24 h. In contrast, the related placenta growth factor mRNA was not induced by TGF-beta in these cells. No VEGF receptor mRNA was seen in AKR-2B cells. Also, TGF-beta treatment of endothelial cells, which express the FLT1 and KDR/FLK-1 receptors for VEGF, did not cause VEGF induction. Because VEGF is known to be a strong angiogenic factor for endothelial cells, the results suggest that the angiogenic effect of TGF-beta on endothelial cells in blood vessels may be mediated at least partly by a paracrine induction of VEGF in other surrounding cell types.

Animals↗

PubMed1994

In vitro angiogenic and proteolytic properties of bovine lymphatic endothelial cells.

The aim of the present study was to determine whether angiogenic cytokines, which induce neovascularization in the blood vascular system, might also be operative in the lymphatic system. In an assay of spontaneous in vitro angiogenesis, endothelial cells isolated from bovine lymphatic vessels retained their histotypic morphogenetic properties by forming capillary-like tubes. In a second assay, in which endothelial cells could be induced to invade a three-dimensional collagen gel within which they formed tube-like structures, lymphatic endothelial cells responded to basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in a manner similar to what has previously been observed with endothelial cells derived from the blood vascular system. Finally, since angiogenesis is believed to require extracellular proteolytic activity, we investigated the effects of bFGF and VEGF on lymphatic endothelial cell proteolytic properties by focussing on the plasminogen activator (PA) system. bFGF and VEGF increased urokinase, urokinase receptor, and tissue-type PA expression. This was accompanied by an increase in PA inhibitor-1, which is thought to play an important permissive role in angiogenesis by protecting the extracellular matrix against excessive proteolytic degradation. Taken together, these results demonstrate that with respect to in vitro morphogenetic and proteolytic properties, lymphatic endothelial cells respond to the previously described angiogenic factors, bFGF and VEGF, in a manner very similar to what has been described for endothelial cells derived from the blood vascular system.

Animals↗

PubMed1994

Role of aging on electrical, mechanical, and coronary modification induced by ouabain and epinine in isolated rat heart.

OBJECTIVE: The contractile response to digitalis and beta adrenoceptor agonists is lower in the senescent than in the adult myocardium, while the development of ventricular arrhythmias is increased. The aim of this study was to examine the effects of aging on cardiac response to digitalis and an adrenergic agonist used clinically. METHODS: The electrical and mechanical responses were tested in isolated and perfused hearts from 3-24 month old rats receiving 15 min infusion of digitalis drug (ouabain, 6 x 10(-5) M) alone, and after 5 min of beta adrenoceptor agonist drug (epinine, 1.5 x 10(-7) M). RESULTS: Ouabain action was associated with a rise in left ventricular end diastolic pressure (p < 0.01) which increased progressively with aging, and with an elevation of left ventricular developed pressure (p < 0.01) which decreased progressively with aging. Epinine induced a reduction of left ventricular end diastolic pressure (p < 0.01) and a rise in left ventricular developed pressure (p < 0.01) but both effects decreased progressively with aging. Ouabain reduced coronary flow and this decrease was more pronounced with aging (p < 0.01), while epinine caused an increase (p < 0.01) that diminished in older hearts. Ouabain given after epinine resulted in a greater increase in left ventricular end diastolic pressure than epinine (p < 0.01) but lower than that caused by ouabain alone (p < 0.01), a greater increase in left ventricular developed pressure than epinine and ouabain (p < 0.01), and a smaller reduction of coronary flow rate than ouabain alone (p < 0.01). All these effects, however, diminished progressively with aging. Arrhythmia scores were higher during ouabain than in control (p < 0.01) and in epinine treated hearts (p < 0.01); pretreatment with epinine did not modify arrhythmia score during ouabain administration. The number and severity of arrhythmias, however, increased with aging in all groups. CONCLUSIONS: Aging has a negative effect on both the positive inotropic and the arrhythmogenic effects of ouabain and epinine, although these phenomena are more pronounced during ouabain administration. However, when the two drugs are given simultaneously, epinine does not modify the arrhythmogenic effect of ouabain but reduces some of its deleterious haemodynamic effects.

Aging↗

PubMed1994

Vascular endothelial growth factor receptor localization and activation in human trophoblast and choriocarcinoma cells.

Vascular endothelial growth factor (VEGF; also known as vascular permeability factor) is a secreted angiogenic growth factor. It is highly specific for endothelial cells, and its receptor, the fms-like tyrosine kinase (flt), has been localized only to endothelial cells in vivo. Here we describe the expression of mRNA encoding flt in human trophoblast as revealed by in situ hybridization. This mRNA is highly expressed in the cytotrophoblast shell and columns and also highly expressed by the extravillous trophoblast (EVT) in the maternal decidua both in the first trimester and at term. The trophoblast-like choriocarcinoma cell line BeWo also expresses this receptor and the related receptor, kinase domain-containing receptor (KDR), which is also a receptor for VEGF. Treatment of the cell line BeWo with VEGF165 stimulated 3H-thymidine incorporation and tyrosine phosphorylation of MAP (mitogen-activated protein) kinase in a time- and dose-dependent fashion. This study is the first demonstration of the presence of flt on non-endothelial cells in vivo and suggests a role for VEGF in the growth and differentiation of cytotrophoblast at implantation.

Base Sequence↗

PubMed1994

Physiological assessment of augmented vascularity induced by VEGF in ischemic rabbit hindlimb.

This study was designed to assess the physiological consequences of augmented vascularity induced by administration of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen, in a rabbit model of hindlimb ischemia. Ten days after excision of the common and superficial femoral arteries from one hindlimb of 24 New Zealand White rabbits, VEGF (n = 15) or saline (control; n = 9) was selectively injected into the ipsilateral internal iliac artery. Limb perfusion was evaluated immediately pre-VEGF (baseline) and again at days 10 and 30. A Doppler guide wire was advanced to the internal iliac artery to record flow velocity at rest and at maximum flow velocity provoked by intra-arterial injection of papaverine. At baseline and at day 10, no differences in flow parameters were observed between the control and the VEGF-treated animals. By day 30, however, flow at rest (P < 0.05), maximum flow velocity (P < 0.001), and maximum blood flow (P < 0.001) were all significantly higher in the VEGF-treated group. These physiological findings complement previous-anatomic studies by providing evidence that a single intra-arterial bolus of VEGF augments flow, particularly maximum flow, in the rabbit ischemic hindlimb. These data thus support the notion that VEGF administration represents a potential treatment strategy for certain patients with lower extremity ischemia.

Animals↗

PubMed1994

Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model.

Vascular endothelial growth factor (VEGF) is a heparin-binding, endothelial cell-specific mitogen. Previous studies have suggested that VEGF is a regulator of naturally occurring physiologic and pathologic angiogenesis. In this study we investigated the hypothesis that the angiogenic potential of VEGF is sufficient to constitute a therapeutic effect. The soluble 165-amino acid isoform of VEGF was administered as a single intra-arterial bolus to the internal iliac artery of rabbits in which the ipsilateral femoral artery was excised to induce severe, unilateral hind limb ischemia. Doses of 500-1,000 micrograms of VEGF produced statistically significant augmentation of collateral vessel development by angiography as well as the number of capillaries by histology; consequent amelioration of the hemodynamic deficit in the ischemic limb was significantly greater in animals receiving VEGF than in nontreated controls (calf blood pressure ratio, 0.75 +/- 0.14 vs. 0.48 +/- 0.19, P < 0.05). Serial angiograms disclosed progressive linear extension of the collateral artery of origin (stem artery) to the distal point of parent vessel (reentry artery) reconstitution in seven of nine VEGF-treated animals. These findings establish proof of principle for the concept that the angiogenic activity of VEGF is sufficiently potent to achieve therapeutic benefit. Such a strategy might ultimately be applicable to patients with severe limb ischemia secondary to arterial occlusive disease.

Angiography↗

PubMed1994

In the human fetus, vascular endothelial growth factor is expressed in epithelial cells and myocytes, but not vascular endothelium: implications for mode of action.

Vascular endothelial growth factor (VEGF) is potentially an important regulator of angiogenesis, particularly during the extensive tissue growth and remodeling that occur in utero. In the present study, we have investigated the role of VEGF during human fetal development by analyzing the distribution of VEGF messenger RNA as well as the tissue- and cell-specific localization of VEGF peptide in the human midgestation (16-22 weeks) fetus. As a comparison, we conducted parallel studies on several human adult tissues. Messenger RNA encoding VEGF was detected in all fetal tissues studied and was most abundant in human fetal lung, kidney, and spleen; moderately abundant in heart, adrenal, pancreas, intestine, liver, testis, skin, muscle, and brain; and minimally detected in thymus and placenta. VEGF peptide, detected by immunohistochemistry, always was intracytoplasmic and localized principally in epithelial cells and myocytes, including the smooth muscle cells lining blood vessels. VEGF was not detected in vascular endothelial cells. As the cellular localization of VEGF in several human adult tissues was similar to that found in the cognate fetal tissues, VEGF is probably important not only in angiogenesis, but also in the maintenance of existing vessels. As VEGF was localized primarily in epithelial cells and myocytes and not in endothelial cells, these data are consistent with a paracrine mechanism of action whereby VEGF secreted by nonendothelial cells modulates activities in adjacent vascular endothelium.

Aging↗

PubMed1994

Intramuscular administration of vascular endothelial growth factor induces dose-dependent collateral artery augmentation in a rabbit model of chronic limb ischemia.

BACKGROUND: Despite major advances in both surgical and percutaneous revascularization techniques, limb salvage and relief of ischemic pain cannot be achieved in many patients with diffuse peripheral vascular disease. Vascular endothelial growth factor (VEGF) is a heparin-binding, endothelial cell-specific mitogen. Previous studies have suggested that VEGF is a regulator of naturally occurring physiological and pathological angiogenesis. In this study, the therapeutic potential of intramuscularly administered VEGF was investigated in a rabbit model of chronic hindlimb ischemia. METHODS AND RESULTS: Ischemia was induced in the hindlimb of 24 New Zealand White rabbits by ligation of the distal external iliac artery and complete excision of the femoral artery. Ten days after the induction of limb ischemia (day 0), saline (group A, n = 7) or the 165-amino acid isoform of recombinant human VEGF (group B: 200 micrograms, n = 6; group C: 500 micrograms, n = 7; group D: 1000 micrograms, n = 4) was administered intramuscularly into the ischemic limb daily for 10 days. Angiography on day 30 after initiation of therapy revealed statistically significant dose-dependent augmentation of collateral vessels in the ischemic limb (angiographic score: group A, 13.0 +/- 1.1; group B, 21.2 +/- 1.8; group C, 27.3 +/- 1.4; group D, 31.5 +/- 2.5). Capillary density in the thigh muscles on day 30 was 1.6 times greater in VEGF groups versus controls (176 +/- 15.3 versus 113 +/- 27.3 per square millimeter, P < .05). Amelioration of the hemodynamic deficit in the ischemic limb was documented by calf systolic blood pressure ratio (group A, 0.52 +/- 0.02; group B, 0.67 +/- 0.02; group C, 0.73 +/- 0.01; group D, 0.82 +/- 0.03). "Clinical" improvement (incidence of calf muscle atrophy and distal limb necrosis: group A, 85.7%; group B, 33.3%; group C, 14.3%; group D, 0%) was greater in VEGF-treated than in control animals, again in a dose-dependent fashion. CONCLUSIONS: These findings demonstrate a significant dose-dependent augmentation in limb perfusion accompanied by evidence of increased collateral formation after intramuscular administration of VEGF in ischemic rabbit hindlimbs. This study thus supports the hypothesis that administration of VEGF to stimulate angiogenesis may represent a new therapeutic modality in the management of arterial insufficiency.

Animals↗

PubMed1993

Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium.

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, induces endothelial proliferation in vitro and vascular permeability in vivo. The human transmembrane c-fms-like tyrosine kinase Flt-1 has recently been identified as a VEGF receptor. Flt-1 kinase has seven immunoglobulin-like extracellular domains and a kinase insert sequence, features shared by two other human gene-encoded proteins, kinase insert domain-containing receptor (KDR) and FLT-4. In this study we show that the mouse homologue of KDR, Flk-1, is a second functional VEGF receptor. Flk-1 binds VEGF with high affinity, undergoes autophosphorylation, and mediates VEGF-dependent Ca2+ efflux in Xenopus oocytes injected with Flk-1 mRNA. We also demonstrate by in situ hybridization that Flk-1 protein expression in the mouse embryo is restricted to the vascular endothelium and the umbilical cord stroma. VEGF and its receptors Flk-1/KDR and Flt-1 may play a role in vascular development and regulation of vascular permeability.

3T3 Cells↗

PubMed1993

Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo.

The development of new blood vessels (angiogenesis) is required for many physiological processes including embryogenesis, wound healing and corpus luteum formation. Blood vessel neoformation is also important in the pathogenesis of many disorders, particularly rapid growth and metastasis of solid tumours. There are several potential mediators of tumour angiogenesis, including basic and acidic fibroblast growth factors, tumour necrosis factor-alpha and transforming factors-alpha and -beta. But it is unclear whether any of these agents actually mediates angiogenesis and tumour growth in vivo. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen and an angiogenesis inducer released by a variety of tumour cells and expressed in human tumours in situ. To test whether VEGF may be a tumour angiogenesis factor in vivo, we injected human rhabdomyosarcoma, glioblastoma multiforme or leiomyosarcoma cell lines into nude mice. We report here that treatment with a monoclonal antibody specific for VEGF inhibited the growth of the tumours, but had no effect on the growth rate of the tumour cells in vitro. The density of vessels was decreased in the antibody-treated tumours. These findings demonstrate that inhibition of the action of an angiogenic factor spontaneously produced by tumour cells may suppress tumour growth in vivo.

Animals↗

PubMed1993

Role of metabolic therapy in cardiovascular disease.

The pathophysiological basis for the use of metabolic therapy in the treatment of heart failure is analyzed. Bioenergetical processes related to ATP bioavailability play a central role in regulating myocardial contractility at rest and on effort. Furthermore, a significant correlation has been demonstrated in diseased heart between ATP content, revealed at endomyocardial biopsy, and systolic and diastolic left ventricular indexes evaluated with invasive and noninvasive methods. Several international investigations demonstrate the beneficial effects of ubiquinone (coenzyme Q10) in the treatment of heart failure. Here the results of a study are reported that was conducted on patients with heart failure treated with ubiquinone. After 7 months of oral drug administration (100 mg/day), a significant improvement was observed in echocardiographic indexes of systolic function, cardiothoracic ratio, and clinical signs and symptoms of congestive heart failure. In conclusion, the introduction of metabolic drugs, such as ubiquinone, in the treatment of heart failure opens new horizons in the therapeutic approach to an ailment that entails substantial human and social costs.

Female↗

PubMed1993

The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF.

Vascular endothelial growth factor (VEGF)mRNA undergoes alternative splicing events that generate four different homodimeric isoforms, VEGF121, VEGF165, VEGF189, or VEGF206. VEGF121 is a nonheparin-binding acidic protein, which is freely diffusible. The longer forms, VEGF189 or VEGF206, are highly basic proteins tightly bound to extracellular heparin-containing proteoglycans. VEGF165 has intermediate properties. To determine the localization of VEGF isoforms, transfected human embryonic kidney CEN4 cells expressing VEGF165, VEGF189, or VEGF206 were stained by immunofluorescence with a specific monoclonal antibody. The staining was found in patches and streaks suggestive of extracellular matrix (ECM). VEGF165 was observed largely in Golgi apparatus-like structures. Immunogold labeling of cells expressing VEGF189 or VEGF206 revealed that the staining was localized to the subepithelial ECM. VEGF associated with the ECM was bioactive, because endothelial cells cultured on ECM derived from cells expressing VEGF189 or VEGF206 were markedly stimulated to proliferate. In addition, ECM-bound VEGF can be released into a soluble and bioactive form by heparin or plasmin. ECM-bound VEGF189 and VEGF206 have molecular masses consistent with the intact polypeptides. The ECM may represent an important source of VEGF and angiogenic potential.

Amino Acid Sequence↗

PubMed1993

Expression of vascular endothelial growth factor does not promote transformation but confers a growth advantage in vivo to Chinese hamster ovary cells.

Vascular endothelial growth factor (VEGF) is a mitogen with a specificity for endothelial cells in vitro and an angiogenic inducer in vivo. We tested the hypothesis that VEGF may confer on expressing cells a growth advantage in vivo. Dihydrofolatereductase--Chinese hamster ovary cells were transfected with expression vectors which direct the constitutive synthesis of VEGF. Neither the expression nor the exogenous administration of VEGF stimulated anchorage-dependent or anchorage-independent growth of Chinese hamster ovary cells in vitro. However, VEGF-expressing clones, unlike control cells, demonstrated an ability to proliferate in nude mice. Histologic examination revealed that the proliferative lesions were compact, well vascularized, and nonedematous. Ultrastructural analysis revealed that capillaries within the lesions were of the continuous type. These findings indicate that the expression of VEGF may confer on cells the ability to grow in vivo in the absence of transformation by purely paracrine mechanisms. Since VEGF is a widely distributed protein, this property may have relevance for a variety of physiological and pathological proliferative processes.

Animals↗

PubMed1993

Developmental expression of binding sites and messenger ribonucleic acid for vascular endothelial growth factor suggests a role for this protein in vasculogenesis and angiogenesis.

Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen and angiogenic inducer produced by a variety of cell lines and tissues. As a soluble protein that exhibits a unique target cell specificity for vascular endothelial cells, VEGF has the potential to play an important role in the development of the vascular system. To better understand the role of VEGF in the processes of vasculogenesis and embryonic angiogenesis, patterns of mRNA expression and [125I]VEGF-binding sites were examined in sections of rat embryos and surrounding tissues during the early stages of development. In situ hybridization revealed the most intense hybridization of VEGF mRNA in the giant trophoblast cells and the mesometrium of early postimplantation specimens. In contrast, only low levels of expression were detected in the embryo until later in embryonic development. Possible embryonic targets for this secreted protein, as identified by displaceable [125I] VEGF binding, were found in association with the early egg sac at E8 and evident in hemangioblasts (blood islands) within the yolk sac at E8-E11. In addition, at all stages, binding was observed along the lumina of blood vessels, of both maternal and embryonic origin. These results provide evidence to support the hypothesis that VEGF plays an important role in the normal development of the embryo and supporting tissues. In the presence of ubiquitous and persistent high affinity binding sites on vascular endothelial cells and precursors, the growth of the vascular system may be regulated in early development by regional expression of VEGF by trophoblast and maternally derived cells, and later on by cells within the embryo as they develop their differentiated phenotype.

Animals↗

PubMed1993

Leukemia inhibitory factor expression in human carotid plaques: possible mechanism for inhibition of large vessel endothelial regrowth.

One common feature of atherosclerotic plaques is the denudation of the endothelium covering the plaque and subsequent failure of endothelial regrowth in contrast to a marked proliferation of neocapillaries arising from the vasa vasorum within the medial wall. Previous studies in vitro have demonstrated the ability of leukemia inhibitory factor (LIF) to potently inhibit aortic endothelial cell growth while only slightly inhibiting the growth of adrenal cortex capillary endothelial cells. This selective effect of LIF on endothelial cells from different sources suggests that it may play a role in the failure of endothelial regrowth in atherosclerosis. Sections of human carotid endarterectomy samples were examined by in situ hybridization for LIF mRNA expression. In one-third of the samples (4/12) examined, cells within the atherosclerotic plaque exhibited LIF expression. Immunohistochemistry of serial sections suggested that the LIF-positive cells were activated macrophages. These results suggest that LIF may play a role in the pathogenesis of atherosclerosis, particularly the denudation of the large vessel endothelium.

Arteriosclerosis↗

PubMed1993

Left ventricular diastolic filling in elderly hypertensive patients.

OBJECTIVE: To evaluate the effects of mild to moderate hypertension and of LVH on diastolic filling and other Doppler indices in the elderly. DESIGN: Survey with a control group. SUBJECTS: Seventy-one hypertensives (34 men, 37 women) referred for echocardiograms and 32 age- and sex-matched normotensive volunteers. Thirty-six of the hypertensives had LVH; 34 did not. SETTING: Echocardiographic laboratory. MEASUREMENTS: M-mode, two-dimensional, and pulsed Doppler echocardiograms. A wide variety of Doppler-derived indices of diastolic function were assessed. RESULTS: All Doppler derived indices of left ventricular diastolic filling (peak E, peak A, their ratio, EF slope, time-velocity integrals, atrial filling fraction, and isovolumic relaxation time) were similar among the three groups. CONCLUSION: Elderly mild to moderate hypertensives with or without LVH have LV diastolic filling that is normal for age. The identification of pathological diastolic dysfunction requires comparison to age-matched controls, since aging, a major factor influencing diastolic filling, can mask the effect of hypertension.

Age Factors↗