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Circulation Research
MAY
1976
VOL. 38
NO. 5
An Official Journal of the American Heart Association
BRIEF REVIEWS
Macromolecules of the Extracellular Compartment of
Embryonic and Mature Hearts
FRANCIS J . M A N A S E K ,
D.M.D.
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THE FORM and function of the heart are the final result of
an integration of cells, tissues, and extracellular material.
The structure of many extracellular macromolecules is
known, but studies of the cardiac extracellular matrix are
still inadequate to provide a comprehensive understanding
of it. The purpose of this review is to summarize the present
knowledge of the cardiac extracellular matrix and to focus
specific attention on this physiologically important compartment. It does not purport to be a detailed review of
extracellular molecules; several excellent recent reviews
exist.1"3
The three general types of macromolecules—collagen,
glycosaminoglycan, and glycoprotein—which are characteristic of extracellular matrices probably differ qualitatively
and quantitatively between different matrices and as a
function of different ages, both pre- and postnatal, in the life
of an animal. These three general classes of macromolecules
will be described briefly after a review of some structural
characteristics of the extracellular matrix.
lamina (synonyms, basement lamina; basal lamella) is a
subunit of the basement membrane which is visible, in most
cases, only with the electron microscope (for terminology,
see References 6 and 7) although some unusually thick basal
laminae such as renal glomerular membrane and Descemet's
membrane are prominent even at the light microscope level.
To date all basal laminae whose composition has been determined appear to contain type IV collagen and glycoprotein,8 but there may be great variability both quantitatively
and qualitatively.
Sometimes the distinction between basement membrane
and basal lamina is not made and the structure is simply
called basement membrane. Confusion has resulted from
inappropriate use of these terms and particularly when cell
coats are called "basement membranes." In the heart, basal
laminae surround capillaries, underlie the endocardium, and
are present along the inner surface of the embryonic
myocardium, whereas myocytes are surrounded by cell
coats.
Microscopic Appearance of Extracellular Space
Chemical Composition of Extracellular Matrix
Ground substance is the material occupying the apparently clear regions interspersed between cells and tissues.
Under appropriate conditions of tissue preservation, ground
substance is preserved, and elicits the metachromatic properties of certain biological stains such as toluidine blue or
Alcian blue, and thus indicates the presence of polyanions.
Embedded in ground substance are collagen and elastin
fibrils: this results in a complex, multiphasic system.
Cell surfaces are covered by a layer of extracellular
material quite distinct from the ground substance.4 This
layer, considered to be glycoprotein on the basis of histochemical staining and called the cell coat or external lamina,
envelops cells without regard for polarity and is found on
mesenchymal cells as well as epithelial cells. It also has been
called the glycocalyx.* Cell surface coats should not be
confused with basement membranes.
Basement membranes are complex extracellular layers of
collagen, glycosaminoglycan, reticular fibers (a form of
collagen), and glycoproteins that underlie the basal surface
(as opposed to apical, or free surface) of epithelia. The basal
Molecular collagen (tropocollagen) is a protein that
consists of three discrete subunits called a chains. The
presence of covalent linkages between a chains reduces their
extractability (as in the case of bone collagen). Lysine,
OH-lysine, and their aldehyde derivatives are involved principally in cross-linking.
There are two general kinds of a chains, termed a\ and
al. Only one type of al chain has been detected, but there
are at least four known a l chains, designated respectively
al(I), al(II), al(III), al(IV). These distinctions are based
on differences in molecular weight, posttranslational characteristics and both amino acid composition and sequence
(for discussion see Reference 1).
Different types of collagen are distinguishable on the basis
of their a chain composition. Type 1 collagen has two a 1(1)
chains and one al chain and is designated |al(I)] 2 a2. All the
other known collagens consist entirely of a l chains. Different collagens are not uniformly distributed in extracellular
matrix (Table I).
It is important to stress that collagen need not assume the
fibrillar, cross-banded form that occurs when tropocollagen
molecules are assembled in a linear, near quarter staggered
array. Thus, absence of histologically demonstrable collagen
bundles or fibrils cannot be equated with the absence of
From the Department of Anatomy. The University of Chicago, Chicago,
Illinois.
Original work reported in this review was supported by Grant HL
13831-04 and by the Louis Block Fund, The University of Chicago.
332
CIRCULATION RESEARCH
VOL.
38, No. 5,
MAY
1976
TABLE I. Chain Composition and Major Distribution of Different Collagen Types
Chain
composition
Major locations
(mature tissues)
Typel
[al(l)] s o2
Skin, bone, tendon
Type 11
(al(II)la
Cartilage
Type III
Type IV
[«I(IID],
tal(IV)],
Skin, dentin, aorta
Some basal laminae
such as lens capsule,
Descemet's membrane.
renal glomerular and
alveolar membranes
Collagen type
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collagen per se, nor can the appearance of fibrils be used to
determine onset of synthesis of molecular collagen.
Collagen types (Table 1) can be identified by denaturing
extracted tropocollagen and identifying a chains according
to a variety of criteria including size, level of proline
hydroxylation, and amino acid composition. Most useful is
the technique whereby collagen a chains are broken at
specific sites by cyanogen bromide into peptides. CNBr
peptides derived from unknown a chains can be compared to
those of known standards.
Glycosaminoglycans (mucopolysaccharides): Glycosaminoglycans (GAGs) are major constituents of ground substance. The GAG molecule is a protein-polysaccharide. As
a matter of convenience we can divide GAGs into sulfated
and unsulfated species. Polysaccharide moieties of different
GAGs are long, unbranched chains of repeating dissacharide
subunits. Carboxylate or ester sulfate groups situated along
the length of the polysaccharide chain result in an overall net
negative charge on the molecule. The polyanionic nature of
GAG polysaccharides results in their histological
demonstrability by means of metachromasia. In physiologically normal situations these negatively charged polysaccharides are associated with cations (counterions), generally
Na + .
Glycoproteins, like GAGs, consist of protein and CHO
moieties. Unlike those of GAGs, glycoprotein carbohydrate
moieties can be branched and contain a greater variety of
carbohydrates. Noncollagenous glycoproteins are major
consistuents of basal laminae 8 - 9 and probably also of cell
coats (glycocalyx or external lamina). 4 Relatively little is
known about the distribution and composition of embryonic
matrix glycoproteins. 10 Some glycoproteins are associated
with cell surfaces and may provide a degree of specificity to
cell surfaces which may be important in cell-cell interactions
during ontogeny."- l2
Extracellular Matrix in the Fully Developed Heart
COLLAGEN
Fibrillar collagen occupies 4% of the extracellular space. 13
Native cardiac collagen is virtually nonextractable in NaCl
or dilute acid. 14 Bovine myocardial collagen (unspecified
age) may be composed of two genetically distinct molecules:
[al(I)]ja2and (a\), with the latter a l chains most similar to
ar 1(1 II). Alpha chains analogous to al(II) or the basal
lamina collagen, al(IV), were not detected in this analysis14
of total myocardial collagen. This is surprising since basal
Typical morphological
appearance in situ
Fibrillar; "typical" 640 A
periodicity
Fibrillar; may or may not
demonstrate periodicity
Fibrillar
Never fibrillar; may be
filamentous component of
basal laminae
laminae are abundantly present in heart tissue. Myocardia
from different regions of the heart were not examined
separately.
VALVULAR COLLAGEN
Heart valves are derived largely from endocardium, via
endocardial cushions. 15 ' 17 Morris and McClain 19 showed
that valvular collagen (veal calf atrioventricular values) is
not extractable in 1 M NaCl or 0.5 M acetic acid. On the basis
of CNBr peptide analysis some homology between valvular
collagen and the [al(II)] s collagen of cartilage was suggested. This apparent molecular homology is intriguing in
light of the report of presumably pathological hyaline
cartilage formation within human aortic valve19 as well as
the normal presence of the fibrocartilaginous corpora Arantii within each leaflet. Absence of detectable amounts of type
IV collagen in valvular tissue is surprising. The endothelium
covering the valvular surface has an unusually thick basal
lamina,20 and the techniques employed should have been
adequate to recover and detect type IV collagen.
GLYCOSAMINOGLYCANS IN VALVE TISSUE
Early compositional analyses of bovine valves21- "
showed the presence of hyaluronate and confirmed the
presence of chondroitin sulfate and dermatan sulfate. The
autoradiographic studies of Mancini et al. 23 showed that
adult rat valves incorporate inorganic sulfate-35 and suggested the synthesis of sulfated GAG. Autoradiographic
analysis of sulfate incorporation in guinea pig valves24
showed a decrease in both incorporation of sulfur-35 and
turnover of sulfated extracellular molecules with age. An
increase in hyaluronidase-resistant materials was correlated
with age. No significant differences were noted between
different valves.
In addition to age-dependent changes in apparent synthesis, the composition of valvular GAGs changes with age.
Moretti and Whitehouse 25 showed the presence of hyaluronate, chondroitin sulfate-6, and dermatan sulfate in both
bovine and porcine valves. Using all valves from 2- to
6-day-old calves and 8- to 10-year-old cattle, they demonstrated a decrease in hyaluronate, a greater decrease in
chondroitin sulfate, and a distinct increase in dermatan
sulfate with age. The presence of hyaluronate, chondroitin
sulfate, and dermatan sulfate in bovine valves was
confirmed26 and later studies 27 suggested that dermatan
sulfate might be associated with collagen, thereby decreas-
CARDIAC EXTRACELLULAR
ing the extractability of both the dermatan sulfate and the
collagen.
NONCOLLAGENOUS GLYCOPROTEINS
Noncollagenous glycoproteins of the mature myocardium
have not been characterized fully but are almost certainly
part of the cell surface coat. 28 Because of their apparent importance in Ca 2+ flux29 it is unfortunate that more is not
known about these molecules. Valve interstitium contains
structural glycoproteins that may prove to be important in
disease states. A review of this topic appeared recently.30
ELASTIN
Elastic fibers have been identified in mature hearts by
routine histological criteria at both the light and electron
microscopic level.
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The Embryonic Cardiac Extracellular Matrix
The early tubular heart contains a prominent sleeve of
extracellular matrix (cardiac jelly) located between the
developing myocardium and the endocardium. Light microscopic studies of fixed material reveal the presence of thin
strands of material in cardiac jelly. Migrating endocardial
cushion cells are associated with these strands. 18 An electron
microscopic study of a human embryo (crown-rump length,
9 mm) identified fibrillar matrix inclusions associated with
endocardial cushion cells. 31 More recently a variety of
morphological techniques have shown the association of
filamentous material with rat endocardial cells.17
Studies using the electron microscope reveal a myocardial
basal lamina that develops concomitantly with the onset of
myofibril assembly and contraction. Fibrillar, cross-banded
collagen is first detectable at about the same time (ca. 10
somites in chick development). Other electron microscopically detectable components 32 remain even more obscure.
Clearly, microscopic examination is not adequate to define
the composition of these regions.
COMPOSITION OF EARLY EMBRYONIC
EXTRACELLULAR MATRIX
Relatively small tissue size makes compositonal analysis
difficult and if careful staging of embryos is to be done, such
analysis is virtually impossible. Recourse to histochemical
techniques33 demonstrates the presence of acidic mucopolysaccharides, and early autoradiographic studies34 showed
incorporation of sulfur-35 into sulfated matrix components.
Autoradiography using staged embryos showed pronounced
labeling of cardiac matrix in the chick using 3 S S O 4 " " or
3
H-glucosamine 3e and in the frog using 3S SO 4 ". 37 Other
studies38- 3" also suggested the presence of glycosaminoglycans. Investigation of both total composition and labeled
molecules with sulfur-3540-41 demonstrated the likely presence of chondroitin sulfate and heparan/heparin sulfate in
the hearts of stage 16-19 (ca. 52 hours) chick embryos.
A histochemical study42 identified hyaluronate (or an
unsulfated carboxylic mucosubstance) and a number of
sulfated GAGs in young rat hearts; concentration was
greatest near the developing endocardium. The synthesis of
hyaluronate, chondroitin, and undersulfated chondroitin
sulfate (on the basis of charge/mass ratio compared to
COMPARTMENT/Manasek
333
standard chondroitin sulfate, as determined electrophoretically) in hearts to stage 11(13 somite, ca. 45 hours embryos)
and, in addition, fully sulfated chondroitin sulfate after
stage 11 was recently shown.43 Heparan sulfate synthesis
was not detected in these studies which used hearts that did
not yet have endocardial cushions. Glycosaminoglycan synthesis during the remainder of cardiogenesis is poorly characterized. Hyaluronate synthesis was detected in 4-day-old
hearts labeled in vitro 44 and sulfate incorporation was shown
to vary as a function of age. 45
COLLAGEN
An early compositional study48 demonstrated the presence of collagen in chick ventricles from day 10 of incubation to 21 days after hatching and suggested that prior to day
19 of incubation collagen accumulated at a rate slower than
that of contractile proteins (measured as actomyosin). After
day 19, collagen and actomysin increased at nearly identical
rates. A later study47 detected collagen in hearts as early as 3
days of incubation, although 5-day-old hearts were the
youngest that contained enough collagen to be measured
quantitatively (their OH-proline analyses required 0.5 g
total tissue) and showed that collagen is formed faster than
net weight increases, indicating that it constantly forms a
greater proportion of the heart. Salt-soluble collagen remains constant (30 M8/g w e t weight) throughout development. However, since the total collagen per gram of tissue
increases constantly, the finding that soluble collagen per
gram remains constant can be interpreted only as indicating
relatively less collagen is soluble as the heart matures.
Soluble collagen was calculated to be about 6% at day 5,
decreasing to 1.5% at day 21 (hatching) and was proportional to newly synthesized collagen, suggesting that newly
synthesized collagen is soluble in neutral salt. These interpretations agree with the seemingly contradictory findings
of McClain,14 who found that mature myocardial collagen
was virtually insoluble in NaCl, and Johnson et al., 32 who
found that newly synthesized collagen in the very early
embryonic heart (made lathyritic) was soluble in neutral
NaCl solution.
To date there has been only one systematic study 32 of
embryonic cardiac collagen synthesis at the time of initial
heart formation. This investigation correlating microscopic
and biochemical findings for the chick detected crossbanded collagen fibrils at about stage 10 (10 somites, 30
hours) and the synthesis of type I-like collagen (detected
biochemically) in lathyritic specimens. Unfortunately total
hydroxyproline synthesis was not measured, so efficiency of
extraction (I M NaCl, 4°C, 3 days) was not determined. This
deficiency in the study becomes important because synthesis
of type IV collagen was not detected even though this study
encompassed the time that myocardial basal laminae were
being formed.32-48- *" Interestingly, type IV-like collagen
was not detected in the compositional studies by McClain,
who used mature myocardium 14 and valves.19 Data available to date suggest therefore that type IV collagen is not
present in detectable amounts in the cardiac interstitium.
Embryonic hearts used by Johnson et al. 32 were all prevalvular (pre-cushion). Thus it seems likely that the type I I-like
valvular collagen is synthesized after these structures ap-
334
CIRCULATION RESEARCH
pear. The decrease in collagen extractability which correlates with age may reflect the interaction of collagen with
glycosaminoglycan. 27
NONCOLLAGENOUS CLYCOPROTEINS
Embryonic cardiac myocytes are surrounded by a cell
coat which is demonstrable by use of ruthenium red (a
cationic dye that binds to polyanions 10 - 50 ) and which
probably represents glycoprotein. It is not known if these
surface coats change in composition during cardiogenesis.
Differences in the staining properties of surface coats of
different types of cells within the myocardium have been
noted" but the significance of, and time of onset of, such
differentiation is not known. Direct evidence for the synthesis of glycoprotein recently has been obtained for early
embryonic hearts49- " but they have not yet been fully
characterized.
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ELASTIN
It is not known when during development elastin is first
synthesized.
Origin of Cardiac Extracellular Macromolecules
It is known that a vast number of non-"connective tissue"
cell types make many extracellular macromolecules. Although it seems likely that fibroblasts produce some, if not
most, of the collagen synthesized in mature hearts it should
be stressed that the myocardium is a heterogeneous structure containing vascular endothelium, vascular smooth
muscle, nerves, and fibroblasts in addition to cardiac
muscle. It is not possible to determine, at the present time,
whether any of these other cell types contribute significantly
to the extracellular matrix. It would be most interesting to
determine the source of the type III -tike a chains.
There are ontogenic events in the chronology of myocardial cellular development that may provide indirect insight
into the course of the different cardiac collagens. Type I-like
collagen is synthesized at a time when the myocardium
contains only developing muscle cells.32 The only other cell
type present in the heart at these stages is primitive
endocardium."• " • 5 4 It is most likely that the developing
cardiac myocytes are elaborating the early type I-like
collagen. This conclusion is consistent with phylogenetic
evidence. Tunicate (hemichordates) hearts lack an endocardium yet have a submyocardial "cardiac jelly" 55 which
contains cross-banded collagen fibrils (see Fig. 5, Reference
55). Anatomical considerations make it unlikely that this
collagen was derived from any source other than the
myocardium. Parenthetically, the rest of the tunicate cardiac matrix is probably also a myocardial product. Seemingly, endocardium is not necessary for the production of the
rudimentary cardiac matrix.
Endocardia! cushions, the precursors of valves, appear at
discrete times in development. It is not known whether this
corresponds to the onset of valvular ( a l ) 3 (presumably type
I I-like) collagen synthesis. Later in development (in the
chick, by about day 4) the other cell types rapidly make
their appearance. 53 Two basic questions that need to be answered are: (1) Does the total collagen synthesized by each
cell remain constant during this transition to a heterogene-
VOL.
38, No. 5,
MAY
1976
ous population? (2) Is this the time of appearance of the
(a\)» collagen molecule?
The use of cell culture techniques to answer these
questions should be attempted with great caution. It is, of
course, possible to grow cells in culture and assay for
collagen synthesis. This approach would reveal whether a
cell type made collagen in culture but could not reveal
whether that same cell type made it in situ. It is hazardous to
ascribe in situ equivalence to cell functions discovered in an
in vitro experiment. Because of the difficulty of providing a
suitable experimental control to the explanation procedure
per se (the control, of course, is in situ), attempts to describe
the molecular composition of a matrix solely by in vitro
studies of synthesis are open to question. It is suggested here
that minimum acceptable criteria for such use of cultured
cells (or tissues) would require that the total product of the
cells grown in vitro account for the total composition,
qualitatively and quantitatively, of the normal matrix in
situ. Note that this requires preexisting knowledge of
normal matrix composition but permits circumvention,
albeit by circumstantial argument, of the usual inability to
show that cells make in situ what they make in culture.
Glycosaminoglycans are produced by undifferentiated
cardiac myoblasts as well as by immature cardiac
myocytes 3S. 36, 43, 52 labeled in situ. Autoradiographic studies also demonstrate myocardial labeling in vitro in chick40
and in frog embryos. 37 Electron microscopic histochemistry
has recently shown acidic glycosaminoglycans in both
myocardium and endocardium. 58 The extensive studies by
Okamoto and his colleagues31 implicate the rat endocardial
cushion cells in production of sulfated matrix. Ueno57 has
quantified sulfate incorporation by rat cushion, but noted
that little label was seen over myocardial or noncushion
endocardial cells. Seemingly, endocardial cushion tissue
becomes a major source of matrix glycosaminoglycan as the
myocardial secretory activity declines.
The heparin (probably heparan sulfate) detected by
Gessner and his colleagues 40 - 41 may represent a maturational change in matrix composition since it was not found
in younger hearts. 43 It is not known when synthesis of
valvular dermatan sulfate25 begins. It is also not known
whether heparan sulfate synthesis continues through development and, if so, where it is localized. Heparan sulfate has
not been detected in mature valves. Neither the cells
producing dermatan sulfate nor heparan sulfate have been
identified, although it may be presumed that valvular
dermatan sulfate is synthesized either by the endocardium or
the endocardial-derived cushion cells.
Matrix contributions from visceral epicardium also are
poorly understood. Fibrillar collagen appears in the subepicardial space during development 53 but no other data,
compositional or synthetic, are available. Subendocardial
connective tissue contains elastic fibers, fibrillar collagen
with a periodicity of 400-580 A, and ground substance, 58 all
of which may be the product of endocardium, fibroblasts,
smooth muscle (origin unknown), or unidentified cells.
The Role of Matrix in Congenital Cardiac Abnormalities
There is a prevailing thought that some congenital
abnormalities may result from abnormal matrix production.
CARDIAC EXTRACELLULAR
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Salicylates inhibit incorporation of 35SO«" into valve
glycosaminoglycan59 and are teratogenic. 60 Other teratogenic agents such as 6-aminonicotinamide, aminopterin, and
trypan blue reduce incorporation of sulfate when administered in vivo or, in the case of trypan blue, also depress
sulfation in vitro. 61 These are all studies of incorporation
and it is not known whether molar or mass synthesis was
depressed since end-product specific activity was not determined. The possibility that the teratogens had a principal
effect elsewhere and depressed sulfate incorporation only as
a secondary, and possibly trivial, side effect was not ruled
out. In contrast to the decrease in sulfate incorporation
resulting from administration of chemical teratogens,
Ueno 57 showed that after 14.1-meV fast neutron irradiation
(130 rads, a cardioteratogenic dose), sulfate incorporation
was actually increased over that of controls. There is no
simple relationship between sulfur incorporation and cardiac malformations and no evidence exists proving that
teratogens alter mass or molar synthesis of cardiac glycosaminoglycan. Pharmacological inhibition of collagen
synthesis' 2 inhibits early cardiac morphogenesis but since it
is impossible to prove that inhibition of collagen synthesis
was the principal, causal lesion these studies were terminated.
Studies on cells in vitro have implicated some extracellular components in the contraction and "spreading" of
cultured heart cells63 and suggesting the dependency of some
physiological parameters on matrix macromolecules.
Matrix composition can change in several ways. A given
cell type (e.g., cardiac muscle) might change its synthetic
pattern, its degradative activity (qualitatively or quantitatively), or both. Changes in cell populations must be
TABLE 2. Cardiac Matrix
considered also, since different cell types (e.g., fibroblasts,
cardiac muscle, endocardium) may make different matrix
components at different rates, at different times. It is known
that myocardial cell populations change during
ontogenesis53 but little is known about cell population
changes in the neonate, juvenile, or mature myocardium.
We cannot ignore these questions if matrix dynamics are to
be understood. Most important, cell population heterogeneity must be considered in establishing culture analogs for
both physiological and biochemical investigation lest uncontrolled variables obscure interpretation.
Conclusions
The extracellular matrix of the heart is not a static, uniform compartment. Its composition seems to change even
in mature hearts, and these changes may be important in
controlling development and function at the level of both the
cell and organ. For example, early in development the elastic properties of the matrix seemingly are essential for diastolic filling.' 5 - 64 At this stage the elasticity is probably
largely a function of the hyaluronate present. *3 This suggests that a single type of extracellular molecule can play a
critical role in early cardiac physiology. It is tempting to
propose that continued presence of these molecules also
contributes to the elasticity of the myocardium in older
hearts.
Comparison of the matrix of normal hearts and those with
acquired disease may provide new insight into the management of heart disease. Similar comparisons between normal
and congenitally malformed hearts may provide insight into
the etiology of such abnormalities. Both qualitative and
quantitative data are needed. The provocative observation
Principal fate of
labeled precursor*
•
fnll'ipen
3
synthesized'
H-GlcN
"SO.-
synthesized
Noncollagenous
glycoprotein
HA,Ch,
UChS
HA.Ch
UChS
Type 1 -like;
other types
(?)
Yes (not characterized)
HA.Ch,
UChS, ChSt
HA, Ch
UChS,
ChS
Yes; type(s)
not characterized
Yes (not characterized)
Older than 18somite chick; by
implication.
mammals also
HA, ChS,
HS(H?),
DS
(?), probably HA
ChS,
HS,
DS
Yes; type(s)
not characterized or
localized
Yes (not characterized)
Postnatal
(mammals)t
HA, ChS,
HS(?),
(?)
ChS,
HS,
DS
Presumably yes
Yes
Stages 9 - I I (7-13
somites, 29-45
hr) labeled in
situ (chick)
Stages 11-13 (1318 somites, 40-51
hr), labeled in situ
(chick)
335
Macromolecules
GlycosaminDevelopmental age
COMPARTMENT/Manasek
DS
Cell types and
tissues present
in heart
Differentiating myocytes;
endocardium; no
"connective tissue"
cells
Differentiated,
functional cardiac
myocytes; endocardium;
no "connective tissue"
cells
Cardiac myocytes;
endocardium;
epicardium:
vascular
components;
fibroblasts; valvular
tissue
Same
• HA = hyaluronate, Ch => chondroitin, UChS = undersulfated chondroitin sulfate, DS _ dermatan sulfate, ChS = chondroitin sulfate, 'H-GlcN = D-glucosamineo-'H.
t Similar glycosaminoglycans have been identified histochemically in rat heart, but no synthetic data are available.
$ Synthesis has not been studied to any significant extent. These data are derived largely from studies of composition that have been assumed to represent
synthesis also.
CIRCULATION RESEARCH
336
that hyaluronidase, an enzyme known to hydrolyze specific
glycosaminoglycans, can alter the course of experimental
myocardial infarcts" suggests yet another way in which the
matrix can influence myocardial responses previously
thought to reside exclusively in myocardial cells.
The regional distribution of different macromolecules
also should be considered if their functions are to be
elucidated. Finally, the dynamics of the cell populations that
produce matrix must be fit into the overall picture. Table 2 is
a brief summary of the present status of cardiac matrix
studies; it should be considered principally as a demonstration of gaps in our knowledge of the acellular compartment
of the heart.
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Macromolecules of the extracellular compartment of embryonic and mature hearts.
F J Manasek
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Circ Res. 1976;38:331-337
doi: 10.1161/01.RES.38.5.331
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