© 1998 American Heart Association, Inc.
Original Contributions |
Early Coronary Angiogenesis in Response to Thyroxine
Growth Characteristics and Upregulation of Basic Fibroblast Growth Factor
From the Department of Anatomy and Cell Biology and the Cardiovascular Center, University of Iowa, Iowa City.
Correspondence to Robert J. Tomanek, PhD, Department of Anatomy and Cell Biology, Bowen Science Bldg, University of Iowa, Iowa City, IA 52242. E-mail robert-tomanek{at}uiowa.edu
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Abstract |
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Abstract—Although a substantial coronary angiogenesis occurs after thyroid hormone treatment, its regulation and relationship to cardiac hypertrophy are not understood. This study was designed to determine (1) the onset of capillary proliferation, (2) the sites of capillary proliferation, and (3) whether basic fibroblast growth factor (bFGF) upregulation occurs in response to thyroxine administration. Male Sprague-Dawley rats were injected daily with L-thyroxine (T4, 0.2 mg/kg SC). Bromodeoxyuridine labeling of capillary endothelial cells increased during the first 24 hours of treatment and peaked after 2 days of treatment. Northern blot analysis revealed a slight increase in bFGF mRNA during this period, followed by a doubling of expression by 48 hours, at which time bFGF protein was also increased. In situ hybridization, used to localize bFGF mRNA, showed an increase in transcripts within 24 hours after T4. This enhancement was uniform in the epimyocardium and endomyocardium. Histochemical analysis (double staining for alkaline phosphatase and dipeptidyl peptidase) of frozen sections, used to discriminate capillary profiles as arteriolar and venular, respectively, showed that growth occurred in the latter, since the percentage of capillary profiles positive for dipeptidyl peptidase was higher than the control value after 4 days of T4 administration. These data indicate that in the thyroxine model of cardiac hypertrophy (1) capillary DNA synthesis occurs after a single injection of thyroxine, (2) capillary growth coincides with an upregulation in bFGF mRNA and increase in bFGF protein, and (3) proliferation occurs in the venular capillaries.
Key Words: cardiac hypertrophy • in situ hybridization • basic fibroblast growth factor mRNA • capillary • microcirculation
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Introduction |
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Cardiac hypertrophy in response to chronically elevated thyroid hormone levels constitutes a model of volume overload leading to eccentric hypertrophy.1 2 3 4 5 6 7 8 9 10 In contrast to pressure-overload hypertrophy, which is often associated with decrements in ventricular function,1 hearts enlarged by thyroid hormone administration have enhanced left ventricular systolic function, including elevated maximal stroke volume1 2 and peak cardiac index.3 Thus, the hearts of hyperthyroid rats exhibit compensated ventricular function, a finding that may be related in part to substantial growth of coronary microvessels that has been documented by many studies.2 5 6 7 8 9 10 We have previously shown that maximal myocardial perfusion is normal or increased in this model.5 9 It is not surprising that this marked angiogenic response is not typical of other models of ventricular enlargement, since the stimulus evoking the cardiac hypertrophy is an important determinant of the response of the coronary vasculature.11 Administration of thyroid hormones causes a number of acute changes in cardiac function, including tachycardia, and increases in cardiac output, rate of change in left ventricular pressure (dP/dt), developed tension, and velocity of shortening (reviewed in References 12 and 1312 13 ). As a consequence of the increased metabolism, oxygen consumption and coronary flow are markedly elevated.14 Enhanced blood flow or increased metabolites linked to increased flow may provide the initial signal for angiogenesis.11 We previously demonstrated that intermittent increases in coronary flow after dipyridamole injection are associated with a 33% increase in coronary capillary length density in rabbits developing cardiac hypertrophy due to hypertension.15
Recent evidence from our laboratory suggests that coronary angiogenesis is not a response to cardiac hypertrophy evoked by thyroxine but that it occurs before significant ventricular enlargement.2 The present study explored the initiation of angiogenesis in this model by testing three hypotheses. Our first hypothesis was that capillary endothelial cell DNA synthesis is initiated during the first 2 days of thyroxine treatment.
The second hypothesis was that bFGF mRNA is enhanced in response to thyroxine treatment and thereby may serve as a mediator for angiogenesis. This hypothesis is based on our finding that bFGF mRNA expression is markedly enhanced during the early period of fetal coronary vascularization and during the early neonatal period when capillary proliferation is particularly high.17 At least three other findings provide a rationale for this hypothesis. First, exogenous bFGF has been shown to increase the number of capillaries and arterioles on the surface of infarcted rat hearts18 and to enhance collateral flow in the ischemic canine heart.19 Second, migration of endothelial cells from bovine coronary arteries is enhanced by bFGF and inhibited by anti-bFGF antibodies.20 Third, cell migration from embryonic hearts onto a collagen gel is enhanced when bFGF is added to the culture medium.21
The third hypothesis was that angiogenesis in the hyperthyroid model occurs preferentially in the venous capillary bed. Rationale for this hypothesis are based on (1) our finding that the relative proportion of venular capillaries is higher in rats 1 month after birth than at 2 months of postnatal life16 and (2) evidence that angiogenesis occurs in both capillaries and venules.17 22 Therefore, a possible explanation of the relatively higher proportion of venous capillaries during the neonatal period is that angiogenesis occurs preferentially in the venous capillary bed.
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Materials and Methods |
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Protocol
T4 (0.2 mg/kg SC) or saline was administered to male Sprague-Dawley rats for a period of 1 to 4 days.23 The day after the last injection, the rats were anesthetized with ketamine (50 mg/kg) and acepromazine (0.5 mg/kg). For bFGF mRNA in situ studies, we used hearts from treated and control rats that were fixed with 2% paraformaldehyde on the Langendorff-type apparatus described in protocol 1, processed, and embedded in Paraplast. Six-micrometer cross sections, stained with Gill's hematoxylin, from these hearts were used. To determine the extent of DNA synthesis in capillary endothelial cells, rats were injected twice (100 mg/kg in 0.1 mol/L IP PBS), 2 hours apart, with BrdU (Sigma Chemical Co), a thymidine analogue that is incorporated in the S phase of proliferating cells. Two hours after the second dose, the rat was anesthetized with ketamine, and the heart was rapidly excised and frozen in OCT compound in isopentane precooled to -80°C. Sections, 4 µm thick, were prepared with a cryostat, placed on polylysine-coated slides, and fixed in 70% ethanol in glycine buffer precooled to -20°C. The sections were then incubated with BrdU primary monoclonal antibody (BrdU detection kit I, Boehringer-Mannheim). Subsequently, the tissue sections were incubated with the secondary antibody (fluorescein-labeled sheep anti-mouse Ig) at 37°C. To indicate all nuclei, the tissues were stained with bisbenzimide H33258 for 15 minutes at room temperature.
To distinguish the arteriolar and venular potions of the capillary bed, we used 13-µm-thick sections cut on a cryostat to localize alkaline phosphatase and DPP IV, respectively.24 General histological analysis was based on sections (2 µm in thickness) from JB4-embedded specimens, which were stained with hematoxylin and eosin. To determine more subtle cellular and extracellular alterations, thin sections of Spurr epoxy resin–embedded specimens were cut with a diamond knife on a Reichert ultramicrotome, stained with uranyl acetate and lead citrate, and examined with a Hitachi H-7000 transmission electron microscope.
In Situ Hybridization
This procedure is identical to that recently published by
us.16 A 395-bp fragment of the coding sequence of
the rat bFGF was cloned into the pGEM 3Zf vector (Promega). The
sequence corresponded to nucleotides 603 to 998 of the
published clone of Shimasaki et al.25 Sense and
antisense RNA transcripts incorporating
[35 S]UTP were produced after restriction
digestion using EcoRI and HindIII, respectively.
The deparaffinized tissue sections were hybridized overnight as
described below.
After proteinase K (1 mg/mL) treatment at 37°C for 30 minutes,
sections were incubated overnight with 50 µL hybridization buffer
(0.3 mol/L NaCl, 20 mmol/L NaAc, 1 mmol/L EDTA, 0.4 mol/L
dithiothreitol, 1x Denhardt's–0.02% Ficoll, 0.02%
polyvinylpyrrolidone, 250 µg/mL yeast tRNA, 10% dextran sulfate, and
50% formamide) containing 
3.6x106 cpm
riboprobe at 50°C. Sections were then treated with 20 µg of RNase A
per milliliter and 1 U RNase T1 per milliliter at
37°C for 15 minutes. After they were washed, the slides were
dehydrated by immersion in graded ethanols containing 0.3 mol/L
ammonium acetate. The sections were air-dried, coated with NTB-2
nuclear tract emulsion, and stored in the dark with desiccant at 4°C
for 2 to 3 weeks. After development, the sections were counterstained
with hematoxylin and coverslipped with mounting medium. In situ
hybridization experiments were performed twice.
For quantitative analysis of grain density, micrographs representing four fields, in various parts of the left ventricle, of each antisense and each sense specimen were photographed using dark-field microscopy. The grains were counted over tissue and nontissue areas, and the latter were subtracted from the former. The net counts of sense were then subtracted from the net counts of antisense.
Quantification of DNA Labeling
In preliminary experiments, we determined that nearly all of the
DNA synthesis in T4-treated rats occurs in
endothelial cells. These data were obtained from
perfusion-fixed hearts from rats that had been injected with either
BrdU or [3H]thymidine before they were killed
for study. Slides from these rats were viewed with an oil-immersion
lens, and the fraction of labeled nuclei was determined. This method
has the advantage of discriminating cell types. We found that
nonmyocyte nuclei constitute 63% of the nuclei in an average
field (43% are endothelial and 20% are
interstitial cells consisting primarily of fibrocytes). In
order to include large numbers of nuclei (1200 per slide), we first
counted nuclei labeled with BrdU using a x40 objective and then
photographed the same fields using an ultraviolet cube to detect nuclei
with the bisbenzimide stain. To be certain that the nuclei labeled with
BrdU were nonmyocytes, the field was viewed alternatively with
polarized light, allowing us to see the myocyte profiles. In order to
express the number of labeled nuclei per nonmyocyte nuclei, we
multiplied the total number by 0.63. Thus, the number of labeled nuclei
is expressed per total nonmuscle nuclei. Since we found that
BrdU-positive nuclei are almost all from endothelial
cells, the percent labeled endothelial cells is an
underestimation.
Northern Blot Analysis
Total RNA was prepared from staged prenatal and postnatal rat
heart tissue using the guanidinium thiocyanate method of Chomczynski
and Sacchi.26 The samples were separated on 1.2%
agarose gels in MOPS buffer containing 6% formaldehyde. The separated
RNAs were transferred overnight onto nylon membrane by capillary action
using 25 mmol/L phosphate buffer, pH 6.5. Completeness of transfer
was checked by viewing the gel under UV light. The RNA transferred onto
the membrane was UV–cross-linked and then prehybridized at 42°C in
50% formamide, 5x SSC (750 mm sodium chloride and 75 mmol/L
sodium citrate, pH 7), 5x Denhardt's solution, 10% SDS, 5% dextran
sulfate, and 20 µg/mL freshly denatured salmon sperm DNA. After 1
hour, 4x106 cpm/mL of freshly denatured
32P-labeled DNA prepared by antisense
transcription, as described for in situ hybridization, was added to the
hybridization solution. The membranes were hybridized overnight at
55°C and then washed twice in 2x SSC and 0.2% SDS and twice in
0.1x SSC and 1% SDS at 50°C. The dried membranes were exposed to
Kodak X-OMAT film. After development, the quantity of mRNA was
standardized to hybridization of the same film to 28S RNA, which served
as an internal standard.
Western Blot Analysis
Western blotting was used to estimate bFGF protein in the left
ventricular samples. Frozen tissue samples were
homogenized in Tris-EDTA buffer containing protease
inhibitors. The homogenate was
centrifuged at 20 000g for 90 minutes, and the
resulting supernatant was applied to a heparin-Sepharose affinity
column. bFGF was eluted with 2 mol/L NaCl–10 mmol/L Tris, pH 7.
This material was concentrated, and protein levels were determined and
separated on a 15% SDS-polyacrylamide gel. The protein bands
were transferred to nitrocellulose, blocked with 5% powdered milk, and
incubated overnight with fibroblast growth factor-2 rabbit polyclonal
antibody diluted 1:400 (Santa Cruz Biotechnology). The nitrocellulose
was washed and blocked as described above and incubated for 1 hour with
anti-rabbit IgG conjugated to horseradish peroxidase. After further
washing, the nitrocellulose was incubated for 1 minute with the ECL
detection reagent (Amersham Life Sciences) and exposed to Kodak X-OMAT
x-ray film for 2 minutes to permit visualization of the protein
bands.
Statistical Analysis
Data are presented as group means (±SEM) and were
analyzed using a one-way ANOVA and a Bonferroni adjustment for
multiple comparisons, with P
.05 selected to denote
statistical significance. Because of unequal variances for the DNA
synthesis data, we used log transformation to reduce the
heterogeneity of variance between groups. An ANOVA was
performed on the transformed values, and the means presented
are to the original scale.
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Results |
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Early Onset of Capillary Proliferation
To determine whether histological or cytological changes occurred in response to early thyroxine treatment, we examined tissues from rats treated for 2 or 4 days. Degenerative changes were not observed with the light microscope. In cross-sectional fields of rats treated for 4 days, we did note the presence of capillary profiles within cardiac myocytes. With the electron microscope such capillary profiles could be seen as being surrounded by a single myocyte profile (Fig 1
). Thus, the capillary growth
associated with thyroxine treatment includes infolding of the
cardiocyte cell membranes, allowing the adjacent capillary to
lie closer to the cell center.
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All data illustrated in Fig 2 are from
rats treated with thyroxine for 4 days. The ratio of heart weight to
body weight in these rats was elevated by 16%. Profiles that were from
the arteriolar and venular ends of the capillary bed (based on alkaline
phosphatase and DPP IV enzyme histochemistry) were quantified in tissue
sections. The percentage of DPP IV (venular)–positive capillaries
increased slightly but significantly in both the
epimyocardium (7%) and endomyocardium (8%)
after 4 days of thyroxine treatment. In both areas of the
myocardium, there was no overlap between the treated and
control individual values. Since capillary numerical density was
unchanged, overall capillary growth kept pace with the myocardial
hypertrophy, and this growth can be accounted for by
proliferation of the venular portion of the capillary bed.
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DNA synthesis of endothelial cells, determined by BrdU
labeling, increased significantly during the first 24 hours after
T4 administration, as noted by a nearly 5-fold
increase over the control value (Fig 3).
After 2 days, BrdU labeling peaked, with a 9-fold increase. By 4 days,
the values were identical to those observed at 1 day. Thus,
endothelial DNA synthesis is a relatively early
response to thyroxine administration and supports the observed increase
in capillarity noted at 4 and 5 days.
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bFGF Expression During Early Thyroxine Treatment
Quantification of bFGF mRNA was determined by densitometric
scanning of autoradiograms (Fig 4). During the first 24 hours after
thyroxine administration, bFGF mRNA tended to increase (15%), and by
48 hours, it doubled. Thus, an increase in message for this growth
factor occurs relatively early during thyroxine administration, and the
increase at 48 hours corresponds to the peak
endothelial DNA synthesis shown in Fig 3
.
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In situ hybridization experiments revealed a fairly uniform labeling
throughout the myocardium (Fig 5). To demonstrate uniformity of grain
distribution throughout the left ventricle, we compared counts from the
four fields used to obtain mean counts. Mean standard deviations were
21% and 16% in the control and treated groups, respectively.
Endomyocardial and epicardial fields were similar
with respect to labeling. Grain counts (counts/1000
µm2, mean±SEM) demonstrate an increase in
transcripts with thyroxine treatment: rats treated for 1 day (n=8),
32.8±3.3 counts/1000 µm2; control rats
(n=7), 20.8±3.9 counts/1000 µm2
(P=.03). In two hearts from rats treated for 2 days, the
values were 42.1 and 53.8 counts/1000 µm2.
These in situ data are very consistent with the findings from
Northern analysis.
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bFGF Protein
Western blot analysis of left ventricles is provided in
Fig 6. Three isoforms of 18, 21, and
22 kD were observed in all experiments and in samples from both control
and T4-treated rats, The density of the 18-kD
isoform was less after 1 day of treatment but then rose to control
levels after 2 days of treatment. After 4 days of treatment, protein
levels for this isoform remained relatively constant or decreased
slightly. Both the 21- and 22-kD isoforms were highest after 2 days of
T4 administration. The density of these bands was
2- to 3-fold higher than that in the control rats. This increase did
not persist, since the two bands after 4 days of
T4 were similar to the control bands.
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Discussion |
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A marked angiogenic response within the myocardium of rats chronically treated with thyroid hormones has been previously documented.4 5 6 7 8 9 10 However, the present study is the first to document the initiation and regulation of angiogenesis. These new findings support several conclusions. First, since DNA synthesis in capillary endothelial cells begins within 24 hours of thyroxine administration, capillary angiogenesis is an immediate response to some acute effect of elevated thyroxine levels. Our second conclusion is that bFGF may play a role in the angiogenic response, since both its mRNA and protein are increased during the first 48 hours after thyroxine administration. Finally, we have documented that proliferation occurs at the venular end of the capillary bed.
Hemodynamic and Metabolic Factors as
Primary Angiogenic Stimuli
A substantial coronary capillary growth that matches the
magnitude of left ventricular enlargement has been shown to
occur within 5 to 10 days of thyroid hormone treatment in
rats4 6 and pigs.7 In
addition, other studies have shown that capillary growth parallels or
exceeds left ventricular hypertrophy when
thyroid hormones are administered for a longer period of
time.5 8 9 Moreover, the angiogenic response
includes resistance vessels, since arteriolar
density7 and maximal coronary
flow5 9 14 are normal. Our recent work documented
a substantial capillary angiogenesis during the first 5 days of
treatment, ie, a 27% increase in length density in the
epimyocardium.2 This finding
suggested that the capillary growth was not a response to cardiac
hypertrophy, since left ventricular mass was
not, as yet, significantly elevated. The present study indicates
that angiogenesis is initiated early and thus appears to be triggered
by the metabolic effects of acutely elevated thyroxine
levels.
Several lines of evidence indicate that the hypertrophic and angiogenic responses to thyroxine are secondary to its hemodynamic and metabolic effects. First, cardiac hypertrophy does not occur in heterotopically transplanted, nonloaded hearts whose hosts were treated chronically with thyroxine.27 Similarly, we have demonstrated that neovascularization in fetal rat hearts, grafted in oculo, where they beat but exist in the unloaded state, is similar in euthyroid, hyperthyroid, and hypothyroid rats.28 Finally, we have shown that coronary capillary growth is not compromised by the hypothyroid state in rabbits.29
Enhancement of coronary flow (or factors associated with such an increase) appears to provide a mechanical stimulus for capillary growth. This thesis is supported by work that documents capillary growth in response to chronic dipyridamole administration in rabbits15 and rats.8 30 Similarly, adenosine or HWA-285, a xanthine derivative, have been found to enhance coronary capillary growth.31 Although adenosine may also directly stimulate endothelial cell proliferation, as demonstrated by in vitro experiments,32 there is evidence that endothelial cells undergo DNA synthesis or proliferation when they flatten33 or are subjected to increases in flow or turbulence.34 Since increased diastolic filling characterizes the thyroxine model, the resulting stretch of the coronary vasculature may provide another mechanical stimulus for microvascular growth. This hypothesis is consistent with data showing that volume-overload–induced cardiac hypertrophy is associated with a proportional growth of capillaries and arterioles.35 Thus, the initial stimulus for a cascade of events that lead to neovascularization in this model is likely to be related to mechanical forces.
Angiogenesis in the Venular Capillary Bed
Using a dual histochemical
procedure,16 24 36 we were able to document that
growth occurs at the venular capillary bed. Alkaline phosphatase is
concentrated in the arteriolar capillaries, whereas the proteinase DPP
IV characterizes venular capillaries and small venules in many species,
including rats and humans.24 Thus, in
longitudinal sections of myocardium, one can visualize a
transition of staining along the course of a capillary
bed.16 36 The significant increase in DPP
IV–positive capillary profiles noted in both the
epimyocardium and endomyocardium of
thyroxine-treated rats documents proliferation of the venular
capillaries. This finding is consistent with evidence that DPP
IV plays a role in angiogenesis, as evidenced by a decline in
angiogenesis when this enzyme is inhibited.37
Capillary numerical density in both myocardial regions was nearly
identical in rats treated with thyroxine for 4 days and their
nontreated controls. There was a 16% increase in heart mass in the
treated group; thus, a significant capillary growth occurred and can be
accounted for by the increase in venular capillary profiles.
Role of bFGF in Angiogenesis
bFGF is a known mitogen for a variety of cell types of mesodermal
and neuroectodermal lineages.38 Therefore,
theoretically, a number of cell types, in addition to
endothelial cells, could be targeted by this growth
factor. However, cardiac myocytes are not known to proliferate in
response to thyroid hormones, and fibroblast hyperplasia is unlikely,
since fibrosis is not characteristic of this model. We have recently
shown that bFGF transcripts are highest in the myocardium
at two time points of development: (1) embryonic days 14 to 15 and (2)
during the first week of postnatal life.16 These
times correspond to an early period of vascularization and to a period
of marked capillary proliferation, respectively. Additionally, in
another study, we showed that migration distance and proliferation of
undifferentiated cells and angioblasts from explanted embryonic hearts
are enhanced with exogenous bFGF in a dose-dependent
manner.21 Our present data show that
upregulation of bFGF mRNA occurs during the first 48 hours of thyroxine
treatment and that the high expression seen at 2 days corresponds to
peak DNA synthesis in endothelial cells. Moreover, bFGF
protein is also highest at this time.
Heretofore, the studies that reported coronary vascular growth in response to exogenous bFGF used models of ischemia.19 20 39 Moreover, pretreatment of isolated rat hearts with bFGF has a protective effect when the hearts are subjected to global ischemia.40 The presence of three bFGF peptide isoforms in heart tissue is consistent with an earlier study.41 That study reported an overall 1.5-fold increase in bFGF in hearts from rats that were administered thyroxine for 4 weeks. Although our data are consistent with this finding, they are based on the onset of thyroxine-stimulated growth, whereas the hearts included in the earlier study most likely were in a stage of limited growth. Thus, they found that the enhancement of bFGF protein was due mainly to an increase in the 18-kD peptide, whereas our increase at 2 days was attributable mainly to a 2- to 3-fold increase in the 21- and 22-kD peptides. The initial decrease of the 18-kD isoform that we observed may be due to its degradation. Mechanical activity may be the stimulus for release of the cytosolic 18-kD isoform of bFGF, since isolated paced ventricular myocytes have been shown to release more of this peptide into the culture medium.42 This increase in release was associated with greater sarcolemmal permeability. The myocytes in that study42 were undergoing hypertrophy that could be blocked by the addition of neutralizing bFGF to the medium. Thus, bFGF may be playing a similar role in our thyroxine model. However, because this growth factor is a major mitogen for endothelial cells and its enhancement corresponds to endothelial cell proliferation, we conclude that it likely plays a role in early angiogenesis in this model.
Although our data show an upregulation of bFGF in response to thyroxine administration, this growth factor may not be singularly affected. Other growth factors cannot be excluded as potential regulators in this model. For example, previous work has shown that bFGF and VEGF have a synergistic effect on the proliferation of bovine capillary endothelial cells.43 Moreover, recent evidence has shown that the exon 6–encoded sequence of VEGF189 exerts its effects through bFGF signaling pathways.44 Accordingly, we do not necessarily view bFGF as the sole mediator of angiogenesis. However, our data indicate that increases in this growth factor coincide with capillary endothelial DNA synthesis; therefore, this mitogen shows an important temporal relationship to the initiation of angiogenesis in response to thyroxine.
Conclusions
The present study explored capillary angiogenesis during the
early period of thyroxine administration. On the basis of several
approaches, we conclude that capillary proliferation is initiated
during the first day of thyroxine treatment, occurs primarily in the
venular capillaries, and may be regulated by bFGF.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This study was supported by National Heart, Lung, and Blood Institute grant HL-48961. The authors gratefully acknowledge the technical assistance of Padma Suvarna, Victoria Struzynski-Olson, and Lei Zheng.
Received May 8, 1997; accepted January 12, 1998.
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References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
1. Friberg P. Diastolic characteristics and cardiac energetics of isolated hearts exposed to volume and pressure-overload. Cardiovasc Res. 1988;22:329–339.[Medline] [Order article via Infotrieve]
2. Tomanek RJ, Busch TL. Coordinated capillary and myocardial growth in response to thyroxine treatment. Anat Rec. In press.
3.
Gay RG, Raya TE, Lancaster LD, Lee RW, Morkin E,
Goldman S. Effects of thyroid state on venous compliance and left
ventricular performance in rats. Am J
Physiol.. 1988;254:H81–H88.
4. Craft-Cormney C, Hansen JT. Early ultrastructural changes in the myocardium following thyroxine-induced hypertrophy. Virchows Arch. 1980;33:267–273.
5.
Chilian WM, Wangler RD, Peters KG, Tomanek RJ, Marcus
ML. Thyroxine-induced left ventricular
hypertrophy in the rat: anatomical and
physiological evidence for angiogenesis. Circ
Res. 1985;57:591–598.
6. Wachtlova M, Ostadal B, Mares V. Thyroxine-induced cardiomegaly in rats of different age. Physiol Bohemoslov. 1985;34:385–395.
7. Breisch EA, White FC, Hammond HK, Flynn S, Bloor CM. Myocardial characteristics of thyroxine stimulated hypertrophy: a structural and functional study. Basic Res Cardiol. 1989;84:345–358.[Medline] [Order article via Infotrieve]
8. Mall G, Zimmer G, Baden S, Mattfeldt T. Capillary neoformation in the rat heart: stereological studies on papillary muscles in hypertrophy and physiologic growth. Basic Res Cardiol. 1990;85:531–540.[Medline] [Order article via Infotrieve]
9.
Tomanek RJ, Connell PM, Butters CA, Torry RJ.
Compensated coronary microvascular growth in senescent rats
with thyroxine-induced cardiac hypertrophy. Am J
Physiol. 1995;268:H419–H425.
10.
Heron MI, Kolar F, Papousek F, Rakusan K. Early and
late effect of neonatal hypo- and hyperthyroidism on coronary
capillary geometry and long-term heart function in rat.
Cardiovasc Res. 1997;33:230–240.
11. Tomanek RJ, Torry RJ. Growth of the coronary vasculature in hypertrophy: mechanisms and model dependence. Cell Mol Biol Res. 1994;40:129–136.[Medline] [Order article via Infotrieve]
12. Freedberg AS, Hamolsky MW. Effects of thyroid hormones on certain nonendocrine organ systems. In: Handbook of Physiology: Endocrinology, Volume III, Thyroid. Washington, DC: American Physiological Society; 1974:435–468.
13. Morkin E, Flink I, Goldman S. Biochemical and physiological effects of thyroid hormone on cardiac performance. Prog Cardiovasc Dis. 1983;25:435–464.[Medline] [Order article via Infotrieve]
14.
Talafih K, Briden KL, Weiss HR. Thyroxine-induced
hypertrophy of the rabbit heart: effect on regional
O2 extraction, flow, and O2
consumption. Circ Res. 1983;52:272–279.
15.
Torry RJ, O'Brien DM, Connell PM, Tomanek RJ.
Dipyridamole-induced capillary growth in normal and
hypertrophic hearts. Am J Physiol. 1992;262:H980–H986.
16. Tomanek RJ, Huang Li, Suvarna PR, O'Brien LC, Ratajska A, Sandra A. Coronary vascularization during development in the rat and its relationship to basic fibroblast growth factor. Cardiovasc Res. 1996;31:E116–E126.
17. Höckel M, Jung W, Vaupel P, Rabes H, Khaledpour C, Wissler JH. Purified monocyte-derived angiogenic substance (angiotropin) induces controlled angiogenesis associated with regulated tissue proliferation in rabbit skin. J Clin Invest. 1988;82:1075–1090.
18.
Yanagisawa-Miwa A, Uchida Y, Nakamura F, Tomlaru T,
Kido H, Kamijo T, Sugimoto T, Kaji K, Utsuyama M, Kurashima C, Ito H.
Salvage of infarcted myocardium of angiogenic action of
basic fibroblast growth factor. Science. 1992;257:1401–1403.
19.
Unger EF, Banai S, Shou M, Lazarous DF, Jaklitsch MT,
Scheinowitz M, Correa R, Klingbeil C, Epstein SE. Basic fibroblast
growth factor enhances myocardial collateral flow in a canine model.
Am J Physiol. 1994;266:H1588–H1595.
20.
Biro S, Yu Z-X, Fu Y-M, Smale G, Sasse J, Sanchez J,
Ferrans VJ, Casscells W. Expression and subcellular distribution of
basic fibroblast growth factor are regulated during migration of
endothelial cells. Circ Res. 1994;74:485–494.
21. Ratajska A, Torry RJ, Kitten GT, Kolker SJ, Tomanek RJ. Modulation of cell migration and vessel formation by vascular endothelial growth factor and basic fibroblast growth factor in cultured embryonic hearts. Dev Dyn. 1995;203:399–407.[Medline] [Order article via Infotrieve]
22. Killingsworth MC. Angiogenesis in early choroidal neovascularization secondary to age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 1995;233:313–323.[Medline] [Order article via Infotrieve]
23.
Tomanek RJ, Butters CA, Zimmerman MB. Initiation of
cardiac hypertrophy in response to thyroxine is not limited
by age. Am J Physiol.. 1993;264:H1041–H1047.
24. Lojda Z. Studies on dipepidyl(amino)peptidase IV (glycyl-proline naphthylamidase), I: blood vessels. Histochemistry. 1979;59:153–166.[Medline] [Order article via Infotrieve]
25. Shimasaki S, Emoto N, Kobu A, Mercado M, Shibata F, Cooksey K, Baird A, Ling N. Complementary DNA cloning and sequencing of rat ovarian basic fibroblast growth factor and tissue distribution study of its mRNA. Biochem Biophys Res Commun. 1988;157:256–263.[Medline] [Order article via Infotrieve]
26. Chomczynski P, Sacchi N. Single step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162:156–159.[Medline] [Order article via Infotrieve]
27. Klein I, Hong C. Effects of thyroid hormone on cardiac size and myosin content of the heterotropically transplanted rat heart. J Clin Invest.. 1990;77:1694–1698.
28.
Rongish BJ, Torry RJ, Tomanek RJ. Coronary
neovascularization of embryonic rat hearts cultured in oculo is
independent of thyroid hormones. Am J Physiol. 1995;268:H811–H816.
29.
Tomanek RJ, Barlow PA, Connell PM, Chen Y, Torry RJ.
Effects of hypothyroidism and hypertension on myocardial perfusion and
vascularity in rabbits. Am J Physiol.. 1993;265:H1638–H1644.
30. Mall G, Schikora I, Mattfeldt T, Bodle R. Dipyridamole-induced neoformation of capillaries in the rat heart. Lab Invest. 1987;57:86–93.[Medline] [Order article via Infotrieve]
31. Ziada A, Hudlicka O, Tyler K, Wright A. The effect of long-term vasodilation on capillary growth and performance in rabbit heart and skeletal muscle. Cardiovasc Res. 1984;18:724–732.[Medline] [Order article via Infotrieve]
32.
Meininger CJ, Schikora I, Mattfeldt T, Granger HJ.
Mechanisms leading to adenosine-stimulated proliferation of
microvascular endothelial cells. Am J
Physiol. 1990;258:H198–H206.
33. Folkman J, Moscona A. Role of cell shape in growth control. Nature. 1978;273:245–249.[Medline] [Order article via Infotrieve]
34.
Davies PF, Remuzi A, Gordon ES, Dewey F, Gimbrone MA.
Turbulent fluid stress induces vascular endothelial
cell turnover in vitro. Proc Natl Acad Sci U S A. 1986;83:2114–2117.
35.
Chen Y, Torry RJ, Baumbach GL, Tomanek RJ. Proportional
arteriolar growth accompanies cardiac hypertrophy induced
by volume overload. Am J Physiol. 1994;267:H2132–H2137.
36. Batra S, Rakusan K. Capillary network geometry during postnatal growth. Am J Physiol. 1993;262:H635–H640.
37. Kohl A, Volk HD, Buntrack P, Kohl G, Diamantstein T, von Baehr. The role of dipeptidylpeptidase IV positive T cells in wound healing and angiogenesis. Agents Actions. 1991;32:125–127.[Medline] [Order article via Infotrieve]
38. Burgess WH, Maciag T. The heparin-binding (fibroblast) growth factor family of proteins. Annu Rev Biochem. 1989;58:575–606.[Medline] [Order article via Infotrieve]
39.
Lazarous DF, Scheinowitz M, Shou M, Hodge E,
Rajanayagam MAS, Hunsberger S, Robinson WG Jr, Stiber JA, Correa R,
Epstein SE, Unger EF. Effects of chronic systemic administration of
basic fibroblast growth factor on collateral development in the canine
heart. Circulation. 1995;91:145–153.
40. Padua RR, Sethi R, Dhalla NS, Kardami E. Basic fibroblast growth factor is cardioprotective in ischemia-reperfusion injury. Mol Cell Biochem. 1995;143:129–135.[Medline] [Order article via Infotrieve]
41. Liu L, Doble BW, Kardami E. Perinatal phenotype and hypothyroidism are associated with elevated levels of 21.5- to 22- kDa basic fibroblast growth factor in cardiac ventricles. Dev Biol. 1993;157:507–516.[Medline] [Order article via Infotrieve]
42. Kaye D, Pimental D, Prasad S, Mäki T, Berger H-J, McNeil PL, Smith TW, Kelly RA. Role of transiently altered sarcolemmal membrane permeability and basic fibroblast growth factor release in the hypertrophic response of adult rat ventricular myocytes to increased mechanical activity in vitro. J Clin Invest. 1997;97:281–291.[Medline] [Order article via Infotrieve]
43. Goto F, Goto K, Weindel K, Folkman J. Synergistic effects of vascular endothelial growth factor on the proliferation and cord formation of bovine capillary endothelial cells within collagen gels. Lab Invest. 1993;69:508–517.[Medline] [Order article via Infotrieve]
44.
Jonca F, Ortéga N, Gleizes P-E, Bertrand N,
Plouët J. Cell release of bioactive fibroblast growth factor 2 by
exon 6-encoded sequence of vascular endothelial growth
factor. J Biol Chem. 1997;272:24203–24209.
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