© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
Cardiac endothelium and myocardial function1
Department of Physiology and Medicine, University of Antwerp, Antwerp, Belgium
* Corresponding author. Tel.: +32 (3) 218-0277; Fax: +32 (3) 218-0276.
Received 29 October 1997; accepted 7 January 1998
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Abstract |
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 Top Abstract 1 Introduction2 Embryological and...3 Functional morphological...4 Functional differences5 Conclusions and perspectivesReferences |
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Endocardial endothelium and vascular endothelium of myocardial capillaries share common features as modulators of cardiac performance, rhythmicity and growth. Growing evidence suggests differences between these two cardiac endothelial cell types with regard to developmental, morphological and functional properties. A major difference probably resides in the way and extent by which these endothelial cells perceive and transmit signals.
KEYWORDS Endocardial endothelium; Vascular endothelium; Myocardial capillary; Endothelial factor; Cytokine; Blood–heart barrier; Cardiac performance
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1 Introduction |
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TopAbstract1 Introduction2 Embryological and...3 Functional morphological...4 Functional differences5 Conclusions and perspectivesReferences |
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Following the observations by Furchgott and Zawadski [1]about the obligatory role of vascular endothelium in vasomotor tone, we presented experimental evidence that cardiac endothelium plays a similar obligatory role in regulating cardiac function.
Modulation of the contractile state of the subjacent cardiomyocytes by endothelial cells in the heart has first been described for the endocardial endothelium (EE) [2–4]and was soon thereafter extended to the vascular endothelium in the myocardial capillaries (MyoCapVE) [5]. Similar observations were subsequently made by numerous investigators in various animal species both in vitro and in vivo [6–12]and several review articles [13–16]have been published on various aspects of the effects of cardiac endothelium and of related cytokines on cardiac function.
From the original experimental observations (Fig. 1), it appeared that the actions of both EE and MyoCapVE on myocardial performance were additive and analogous – if not identical; these common features were ascribed to changes in the affinity of the contractile proteins for Ca2+ [3, 4, 18, 19]. More recent work from our laboratory [20, 21]has demonstrated, however, that despite these apparent similarities EE and MyoCapVE display major functional and conceptual differences.
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This is not surprising in view of their different embryological origin and given the fact that the immense EE surface is continuously exposed to all of the circulating blood, whereas the MyoCapVE is reached by only 3–5% of it. From this; one would be tempted to speculate that, as we will discuss below, the EE, in contrast to MyoCapVE, would also act as a sensing system: the total circulating amount (concentration or partial pressure times cavitary flow) of various humoral factors would be more important rather than their concentration or partial pressure. By contrast, the MyoCapVE is, at least in most of the left ventricular wall, exposed to the larger fraction of subjacent cardiomyocytes; the concentration gradient or partial pressure difference of the circulating stimuli would be more important in light of optimal diffusion and for local endothelial modulation of the underlying myocardium.
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2 Embryological and developmental differences |
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TopAbstract1 Introduction2 Embryological and...3 Functional morphological...4 Functional differences5 Conclusions and perspectivesReferences |
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In the embryo, the heart develops from the precardiac lateral fold to form the primitive heart tube. This tube consists of an inner EE tube which is separated from the outer myocardial tube by the elastic amorph cardiac jelly. EE cells and cardiomyocytes appear at about the same time during development and at first develop rather independently from one another [22]. Subsequently, the EE cells invade the cardiac jelly and migrate towards the myocardial tube. Soon thereafter, the EE as the sole cardiac endothelial cell monolayer lines most of the cardiomyocytes. Together, EE and cardiomyocytes constitute the primitive spongious heart tube, and the first cardiac contractions appear at about this stage. In mutant Zebrafish embryo lacking an EE tube, the developing myocardial tube remained somewhat smaller and dysmorphic, but was capable of initiating spontaneous contractions; contractility was, however, markedly reduced with distended atria and collapsed ventricles and the animals did not survive long thereafter [23].
The obligatory role of the EE in myocardial cell maturation and function at subsequent stages of embryonic development has been confirmed more recently after the discovery of the neuregulin growth factor signalling pathway in the EE (Fig. 2) [24]. At an early embryological stage, neuregulin expression is confined to the EE from where neuregulin is released as a paracrine neuregulin growth signal to be received by the ErbB2 and ErbB4 receptors. These receptors are expressed on nearby cardiomyocytes. Activation of both receptors is required for subsequent trabeculation of the primitive spongious heart. Trabeculation is essential for normal functioning of the heart and for the survival of the animal. Mutant embryos lacking either one of these three genes exhibit no trabeculation and die in utero at an early stage [25–27].
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At a much later stage, more compact myocardium develops in the periphery of the developing heart. The formation of compact myocardium is followed by the penetration of small buds of primitive coronary vessels invading it from the epicardial surface. Subsequent development of a myocardial vascular plexus and the establishment of a mature coronary circulation are relatively late events, the phylogenetic and embryological importance of which depending entirely upon the ratio of compact-to-spongious myocardium [20, 28]. The appearance in the early MyoCapVE of functional features, as e.g. ecNOS expression and hence probably also the direct modulation of the performance of subjacent cardiomyocytes, significantly lags behind their presence in the EE (L. Andries, unpublished observations, [29]).
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3 Functional morphological differences |
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TopAbstract1 Introduction2 Embryological and...3 Functional morphological...4 Functional differences5 Conclusions and perspectivesReferences |
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In vertebrates, the luminal surface of the mature heart has a complex structure consisting of furrows, cylinder- and sheet-like trabeculae and papillary muscles. In the human heart, the architecture of the ventricular wall is usually more elaborate in the right than in the left ventricle; in the latter ventricle, trabeculations are more densely organized at the apex and posterior wall than on the septum whose surface is usually smooth. The complex cavitary surface of the ventricular wall is completely lined by the EE. It can be estimated that the labyrinth of trabeculae and furrows, and, even more so, the numerous microvilli on the luminal surface of the EE cells may augment by a factor of 100 or more the available contact surface area which separates the EE from the superfusing blood. As a consequence, this surprisingly large contact surface area of the EE offers an astonishingly high ratio of cavitary surface area to ventricular volume (more so in the right than in the left ventricle), suggesting an important sensor function for the EE.
The intercellular clefts between EE cells are 3–5 times as deep as in MyoCapVE. In the EE (Fig. 3), the clefts are often highly tortuous with two or three cells imbricated and most contain one or two tight junctions. Depending on age and on species, EE cells in some areas (compare A and C in Fig. 3) can be separated by clefts that are more simple, less deep and without tight junctions. By contrast, in MyoCapVE, most clefts are simple, shallow and exhibit few tight junctions with many interruptions [31]. As a consequence, the degree of cellular overlap in the EE exceeds that in MyoCapVE by at least 3–5 times. This was recently endorsed by experiments in which cardiac endothelial cells were stained with antibodies against the platelet and endothelial cell adhesion molecule PECAM-1 (Fig. 4A,B). PECAM belongs to the immunoglobulin superfamily and participates in the establishment and maintenance of barrier function and permeability in many endothelia [32, 33]. In the EE, PECAM staining is typically confined to the borderzone of the EE cells corresponding to the zone of cellular overlap and intercellular clefts [21]. By contrast in MyoCapVE, PECAM stained more diffusely over the entire cell surface. Hence, although present in both cell types, the pronounced differences in distribution of PECAM suggest profound differences in transendothelial permeability between these two cardiac sites.
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Transendothelial transport is believed to be mediated either by diffusion through the intercellular clefts, or by non-diffusional vesicular transport, or through cell–matrix junctions i.e. focal adhesion contacts [34]. The paucity of central actin stress fibres in most cavitary EE cells, which limits the adhesion to substrate matrix proteins, also suggests that transport through focal adhesion contacts is probably of lesser importance. Moreover, the abundance of vesicles in MyoCapVE compared to the scarcity of vesicles in EE suggests that vesicular transport would also be less prominent in EE than in MyoCapVE. It would thus appear that trans-EE-permeability is predominantly controlled through the clefts, as mediated through: (1) their extent and complex structure lined by a dense electrically charged glycocalyx; (2) the presence of one or two tight junctions (zonula occludens); and (3) the presence of a well-organized zonula adherens with complex interactions between a circumferential actin filament band and several connecting proteins as, for example, vinculin etc. Co-staining of EE for actin and for non-muscle myosin has suggested that trans-EE-permeability changes could be mediated not only by stretch [35]or by passive retraction of the EE cells, e.g. by phosphorylation of actin-linking proteins such as vinculin and
-catenin, but also in a more active way by activation of these actin–myosin interactions. Apart from these fundamental differences in the control of transendothelial permeability, EE and MyoCapVE also differ in the way they communicate with other both adjacent endothelial and subjacent non-endothelial cells [20]. The abundance of gap junctions between EE cells (Fig. 4C), as evident from TEM and immunostaining with several connexins (Cx43, Cx40, Cx37) and their absence in MyoCapVE (Fig. 4D) suggests that EE displays an intimate electrochemical linkage between EE cells. This type of communication would allow for rapid intercellular electrochemical spreading of the functional properties of the EE even after activation of only a single EE cell; the resulting amplification mechanism would be, moreover, in accordance with the above-suggested sensor function. By contrast, the probable lack of gap junctions in MyoCapVE suggests a more local regulatory control of myocardial function. In addition, with respect to the various adhesion molecules, hence the possibility for communicating with non-endothelial cell types, major differences were observed; with, for example, intercellular adhesion molecule (ICAM-1) and antigens of the major histocompatibility complex (MCHI, MCHII and DR) being more prominent in MyoCapVE than in EE, PECAM exhibiting major differences in cellular distribution as indicated above, and the endothelial marker PAL-E as well as von Willebrand's factor being abundant in EE and hardly at all in MyoCapVE. Finally, recent immunostaining of cardiac tissue for endothelial constitutive NO synthase (ecNOS; Fig. 4E,F) has shown that ecNOS in EE is highly concentrated in the Golgi bodies [21]. From these experiments, it appeared that Golgi bodies in EE by far exceeded in size those in MyoCapVE, suggesting a much higher metabolic synthetic capacity of EE. Moreover in EE, ecNOS also typically stained the borderzone, thereby labelling the same zone as after staining with PECAM. From this observation and from recent evidence showing cGMP-mediated changes in endothelial permeability [36], one could speculate that the ecNOS-cGMP signalling pathway could also be involved in the complex regulation of trans-EE permeability.
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4 Functional differences |
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TopAbstract1 Introduction2 Embryological and...3 Functional morphological...4 Functional differences5 Conclusions and perspectivesReferences |
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Both EE and MyoCapVE express and release substances or messengers (Fig. 5), as, for example, nitric oxide (NO) [7, 21, 38], prostacyclin (PGI2) [39], endothelin (Et) [40], previously demonstrated for most other vascular endothelial cells. As the three substances regardless of their cell of origin, i.e. EE or MyoCapVE, have been shown to possess inotropic properties on the myocardium [8, 41–43], it is not surprising that it was generally believed that EE and MyoCapVE should have (as also suggested from our original observations illustrated in Fig. 1) similar, if not identical, and additive effects on cardiac function. There is, however, recent experimental evidence that a more refined view is necessary.
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First, the expression of ecNOS in cardiac tissue exhibits major non-uniformities in distribution [21]. In EE cells, ecNOS is abundantly present and predominantly confined to the Golgi body and the borderzone corresponding to the cleft region. By contrast, in MyoCapVE, ecNOS expression is significantly more faint and more diffusely distributed in the cytoplasm with only a little more dense concentration in the very small Golgi bodies. In addition, the beating heart exhibited cyclic changes in NO concentration which peaked at three times higher concentrations near the endocardium than in the mid-ventricular myocardium [44]. This could suggest that the inotropic action on subjacent cardiomyocytes would be much less prominent in myocardial capillaries than in the EE, where, in addition, as suggested above, the ecNOS–NO–cGMP signalling pathway could also be involved in the control of trans-EE-permeability. On the other hand, one could equally speculate that NO from capillaries would, despite the lower ecNOS expression, have a relatively more prominent action because of the much smaller diffusion distance compared to the distance between EE cells and cardiomyocytes. A possible association between ecNOS and caveolin-1 is discussed elsewhere [21]. Although no such non-uniformities in distribution have as yet been described for Et or PGI2, there is some indirect evidence that EE releases PGI2 more abundantly than MyoCapVE [39]. However, this awaits, further confirmation.
Second, simultaneous inhibition of NO, PGI2 and Et by L-NMMA, indomethacin and BQ123 in isolated papillary muscle resulted in little effect on baseline contractile performance [45]; this contrasted with the profound effect on performance when the EE had been selectively damaged as in Fig. 1.
These observations, together with the above-described functional morphological trans-EE-permeability features, further endorse our view [4, 20]that EE would, in addition to the release of substances with inotropic potential, perhaps also act as an active physicochemical barrier (Fig. 5).
What evidence do we have at present that the EE would, by analogy with the capillary endothelium of the blood–brain barrier, function as a blood–heart barrier?
Similarly to brain capillary VE, EE cells are electrically highly active cells. Recent, electrophysiological studies in EE revealed the presence of a large number of membrane ion channels (inwardly rectifying K+ channels, Ca2+-activated K+ channels, background Cl– and cation channels, volume-activated Cl– channels, stretch-activated cation channels) and, at least, one carrier-mediated transporter (Na+,K+-ATPase) [46–50]. Although presumed to be electrically silent in the sense that they do not display regular action potentials, such as cardiomyocytes or neurons, EE cells do have an intense transmembrane transport of ions. Transcellular transport of ions by passive diffusion through ion channels or by active carrier-mediated transport may contribute to a directed transport of ions from the blood to the cardiomyocytal interstitium and vice versa. The asymmetrical localization of non-selective cation channels on the luminal membrane of EE cells [51]and possibly also of the Na+,K+-ATPase (presently under investigation) would suggest a net transport of K+ from the heart to the blood and of Na+ from the blood to the heart as has been described for the microvascular endothelium of the blood–brain barrier [52, 53]. Highly excitable tissues, such as the brain and myocardium, indeed necessitate high interstitial [Na+] to guarantee a rapid upstroke of the action potential and a low interstitial [K+] to stabilize the membrane resting potential. Given the more leaky MyoCapVE, modulation of the interstitial ionic homeostasis by the EE would be expected to be confined to the immediate subendocardial myocardial layers, including the terminal Purkinje fiber network and the dense subendocardial neural plexus.
A unique feature of the blood–brain endothelial barrier is the high transendothelial electrical resistance (TEER) of 1500–2000 
cm2 when compared with other endothelia (TEER=6–20 cm2) [54]. TEER values for EE cells have not been published. In preliminary experiments, we measured TEER values of 50–60 cm2 in near-confluent monolayers of cultured porcine right ventricular EE (unpublished observations); these values were 2–5 times higher than in other endothelia and suggest that EE can function as an active barrier between the circulating blood and the cardiomyocytal interstitium. Intercellular coupling between EE cells was further investigated by combining electrophysiological techniques with dye-spreading fluorimetry. Results indicated that EE cells were not only electrically coupled, but also dye-coupled [55]. The syncytial character of EE is expected to be important as an amplification factor not only in the release of endothelium-derived inotropic substances as suggested above, but also in the putative barrier function of the EE regulating the unidirectional transcellular transport of ions.
Accordingly, there is growing functional morphological and electrophysiological evidence to support the concept of EE as an active blood–heart barrier. Apart from its role as a sensor device for the circulating blood and as a paracrine-mediated regulator of myocardial performance, in particular, in the right ventricle, such an active EE blood–heart barrier could be of utmost importance for the overall ionic homeostasis of the interstitial milieu surrounding the highly excitable myocardium, as well as for the immediate subjacent terminal Purkinje fiber network and the dense subendocardial neural plexus [56](Fig. 5). Interaction of the EE with these latter two structures, in particular the role of EE in the control of conduction and rhythmicity awaits further experimental evidence.
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5 Conclusions and perspectives |
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TopAbstract1 Introduction2 Embryological and...3 Functional morphological...4 Functional differences5 Conclusions and perspectivesReferences |
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Although EE and MyoCapVE share common features in their effects on subjacent cardiomyocytes, there is growing evidence that these two cardiac endothelial cell types are not identical. They differ with regard to developmental, morphological and functional properties, the major difference probably resulting from their different position and contribution within the overall endothelial system. EE may function at two levels of decision making: (1) as a sort of (differential) sensor device receiving all the circulating blood entering and leaving the pulmonary vasculature; and (2) as an autocrine or paracrine organ-oriented modulator of cardiac performance, of rhythmicity and of growth; the relative importance of the latter three functional aspects probably being (i.e., right versus left) ventricle-specific.
By contrast, MyoCapVE possibly functions as a mere autocrine or paracrine organ-specific modulator of cardiac performance, of rhythmicity and of growth. MyoCapVE receives less than 5% of cardiac output, but controls, at least in the left ventricular wall, the larger portion of myocardial muscle mass.
In medicine, the development of physiological concepts is often inspired by clinical problems. This reasoning explains, in part, the major emphasis received by the coronary VE and, more recently also by the MyoCapVE, given their obvious role in the etiology and pathogenesis of atherosclerosis and ischemic cardiomyopathy. The question which of the above two cell types, the EE or the MyoCapVE, would be the more important one for cardiac function is, however, less relevant. Both are essential for the normal functioning of the heart; their major difference probably residing in the way and extent by which EE and MyoCapVE perceive and transmit signals.
Time for primary review 26 days.
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Notes |
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1 This Review is a summary of the Basic Science Lecture delivered by Dirk L. Brutsaert at the Annual Scientific Meeting of the ESC, Stockholm (Sweden), August 27, 1997.
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References |
|---|
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TopAbstract1 Introduction2 Embryological and...3 Functional morphological...4 Functional differences5 Conclusions and perspectivesReferences |
|---|
- Furchgott RF, Zawadski JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature (1980) 288:373–376.[CrossRef][Medline]
- Brutsaert DL, Meulemans AL, Sipido KR, Sys SU. Endocardial control of myocardial performance. In: Sugi H, Pollack GD, editors. Molecular mechanism of muscle contraction. Proceedings of the 1986 Muscle Symposium. Hakone: Plenum, 1986:609–616.
- Brutsaert DL, Meulemans AL, Sipido KR, Sys SU. Effects of damaging the endocardial surface on the mechanical performance of isolated cardiac muscle. Circ Res (1988) 62:358–366.
[Abstract/Free Full Text] - Brutsaert DL. The endocardium. Annu Rev Physiol (1989) 51:263–273.[CrossRef][Web of Science][Medline]
- Li K, Rouleau JL, Andries LJ, Brutsaert DL. Effect of dysfunctional vascular endothelium on myocardial performance in isolated papillary muscles. Circ Res (1993) 72:768–777.
[Abstract/Free Full Text] - Smith JA, Shah AM, Lewis MJ. Factors released from endocardium of the ferret and pig modulate myocardial contraction. J Physiol (Lond) (1991) 439:1–14.
[Abstract/Free Full Text] - Balligand JL, Kelly RA, Marsden PA, Smith TW, Michel T. Control of cardiac muscle cell function by an endogenous nitric oxide signalling system. Proc Natl Acad Sci USA (1993) 90:347–351.
[Abstract/Free Full Text] - Li K, Stewart DJ, Rouleau JL. Myocardial contractile actions of endothelin-1 in rat and rabbit papillary muscles. Role of endocardial endothelium. Circ Res (1991) 69:301–312.
[Abstract/Free Full Text] - De Hert SG, Gillebert TC, Brutsaert DL. Alteration of left ventricular endocardial function by intracavitary high-power ultrasound interacts with volume, inotropic state, and alpha 1-adrenergic stimulation. Circulation (1993) 87:1275–1285.
[Abstract/Free Full Text] - Paulus WJ, Vantrimpont PJ, Shah AM. Paracrine coronary endothelial control of left ventricular function in humans. Circulation (1995) 92:2119–2126.
[Abstract/Free Full Text] - Nishida M, Springhorn JP, Kelly RA, Smith TW. Cell–cell signaling between adult rat ventricular myocytes and cardiac microvascular endothelial cells in heterotypic primary culture. J Clin Invest (1993) 91:1934–1941.[Web of Science][Medline]
- McClellan G, Weisberg A, Rose D, Winegrad S. Endothelial cell storage and release of endothelin as a cardioregulatory mechanism. Circ Res (1994) 75:85–96.
[Abstract/Free Full Text] - Shah AM. Paracrine modulation of heart cell function by endothelial cells. Cardiovasc Res (1996) 31:847–867.
[Abstract/Free Full Text] - Winegrad S. Endothelial cell regulation of contractility of the heart. Annu Rev Physiol (1997) 59:505–525.[CrossRef][Web of Science][Medline]
- Brutsaert DL, Andries LJ. The endocardial endothelium. Am J Physiol (1992) 263:H985–H1002.[Web of Science][Medline]
- Brutsaert DL. Endocardial and coronary endothelial control of cardiac performance. NIPS (1993) 8:82–86.
[Abstract/Free Full Text] - Sys SU, Brutsaert DL. Endocardial endothelium: control of cardiac performance. Austin, TX: Landes/Heidelberg: Springer, 1995.
- Wang J, Morgan JP. Endocardial endothelium modulates myofilament Ca2+-responsiveness in aequorin-loaded ferret myocardium. Circ Res (1992) 70:754–760.
[Abstract/Free Full Text] - Shah AM, Mebazaa A, Yang ZK, et al. Inhibition of myocardial crossbridge cycling by hypoxic endothelial cells. A potential mechanism for matching oxygen supply and demand? Circ Res (1997) 80:688–698.
[Abstract/Free Full Text] - Brutsaert DL, De Keulenaer GW, Fransen P, et al. The cardiac endothelium: functional morphology, development, and physiology. Prog Cardiovasc Dis (1996) 39:239–262.[CrossRef][Web of Science][Medline]
- Andries LJ, Brutsaert DL, Sys SU. Nonuniformity of ecNOS distribution in cardiac endothelium. Circ Res 1998;82:195–203.
- Sugi Y, Markwald RR. Formation and early morphogenesis of endocardial endothelial precursor cells and the role of endoderm. Dev Biol (1996) 175:66–83.[CrossRef][Web of Science][Medline]
- Stainier DYR, Weinstein BM, Detrich HW, Zon LI, Fishman MC. Cloche, an early acting zebrafish gene, is required by both the endothelial and hematopoietic lineages. Development (1995) 121:3141–3150.[Abstract]
- Marchionni MA. Neu tack on neurogulin. Nature (1995) 378:334–335.[CrossRef][Medline]
- Meyer D, Birchmeier C. Multiple essential functions of neuregulin in development. Nature (1995) 378:386–390.[CrossRef][Medline]
- Gassmann M, Casagranda F, Orioll D, et al. Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor. Nature (1995) 378:390–394.[CrossRef][Medline]
- Lee KF, Simon H, Chen H, et al. Requirement for neuregulin receptor erbB2 in neural and cardiac development. Nature (1995) 378:394–398.[CrossRef][Medline]
- Andries LJ. Endocardial endothelium: functional morphology. Austin, TX: Landes, 1994.
- Ursell PC, Mayes M. Endothelial isoform of nitric oxide synthase in rat heart increases during development. Anat Rec (1996) 246:465–472.[CrossRef][Medline]
- Andries LJ, Brutsaert DL. Endocardial endothelium: junctional organization and permeability. Cell Tissue Res (1994) 277:391–400.[Web of Science][Medline]
- Bundgaard M. The three-dimensional organization of tight junctions in a capillary endothelium revealed by serial-section electron microscopy. J Ultrastruct Res (1984) 88:1–17.[CrossRef][Web of Science][Medline]
- Dejana E, Del Maschio A. Molecular organization and functional regulation of cell to cell junctions in the endothelium. Thromb Haemost (1995) 74:309–312.[Web of Science][Medline]
- Ferrero E, Ferrero ME, Pardi R, Zocchi MR. The platelet endothelial cell adhesion molecule-1 (PECAM1) contributes to endothelial barrier function. FEBS Lett (1995) 374:323–326.[CrossRef][Web of Science][Medline]
- Lum H, Malik AB. Mechanisms of increased endothelial permeability. Can J Physiol Pharmacol (1996) 74:787–800.[CrossRef][Web of Science][Medline]
- Page E, Upshaw-Earley J, Goings G. Permeability of rat atrial endocardium, epicardium, and myocardium to large molecules. Stretch-dependent effects. Circ Res (1992) 71:159–173.
[Abstract/Free Full Text] - Hempel A, Noll T, Muhs A, Piper HM. Functional antagonism between cAMP and cGMP on permeability of coronary endothelial monolayers. Am J Physiol (1996) 270:H1264–H1271.[Medline]
- Fransen P, Demolder M. Physicochemical properties of the endocardial endothelium. In: Sys SU, Brutsaert DL, editors. Endocardial endothelium: control of cardiac performance. Austin, TX: Landes/Heidelberg: Springer, 1995:57–80.
- Schulz R, Smith JA, Lewis MJ, Moncada S. Nitric oxide synthase in cultured endocardial cells of the pig. Br J Pharmacol (1991) 104:21–24.[Web of Science][Medline]
- Mebazaa A, Wetzel R, Cherian M, Abraham M. Comparison between endocardial and great vessel endothelial cells: morphology, growth, and prostaglandin release. Am J Physiol (1995) 268:H250–H259.[Web of Science][Medline]
- Mebazaa A, Mayoux E, Maeda K, et al. Paracrine effects of endocardial endothelial cells on myocyte contraction mediated via endothelin. Am J Physiol (1993) 265:H1841–H1846.[Web of Science][Medline]
- Mohan P, Brutsaert DL, Sys SU. Myocardial performance is modulated by interaction of cardiac endothelium derived nitric oxide and prostaglandins. Cardiovasc Res (1995) 29:637–640.
[Abstract/Free Full Text] - Mohan P, Brutsaert DL, Paulus WJ, Sys SU. Myocardial contractile effects of nitric oxide and cGMP. Circulation (1996) 93:1223–1229.
[Abstract/Free Full Text] - Kojda G, Kottenberg K, Nix P, et al. Low increase in cGMP induced by organic nitrates and nitrovasodilators improves contractile response of rat ventricular myocytes. Circ Res (1996) 78:91–101.
[Abstract/Free Full Text] - Pinsky DJ, Patton S, Mesaros S, et al. Mechanical transduction of nitric oxide synthesis in the beating heart. Circ Res (1997) 81:372–379.
[Abstract/Free Full Text] - De Keulenaer GW, Fransen P, Brutsaert DL, Sys SU. Decreased myocardial contractility after damage to endocardial endothelium is not merely caused by loss of endothelin production. Cardiovasc Res (1995) 30:646–647.
[Free Full Text] - Laskey RE, Adams DJ, Johns A, Rubanyi GM, van Breemen C. Membrane potential and Na+-K+ pump activity modulate resting and bradykinin-stimulated changes in cytosolic free calcium in cultured endothelial cells from bovine atria. J Biol Chem (1990) 265:2613–2619.
[Abstract/Free Full Text] - Hoyer J, Distler A, Haase W, Gogelein H. Ca2+ influx through stretch-activated cation channels activates maxi K+ channels in porcine endocardial endothelium. Proc Natl Acad Sci USA (1994) 91:2367–2371.
[Abstract/Free Full Text] - Fransen PF, Demolder MJM, Brutsaert DL. Whole cell membrane currents in cultured pig endocardial endothelial cells. Am J Physiol (1995) 268:H2036–H2047.[Web of Science][Medline]
- Manabe K, Takano M, Noma A. Non-selective cation current of guinea-pig endocardial endothelial cells. J Physiol (Lond) (1995) 487:407–419.
[Abstract/Free Full Text] - Fransen P, Sys SU. K+ and Cl– contribute to resting membrane conductance of cultured porcine endocardial endothelial cells. Am J Physiol (1997) 272:H1770–H1779.[Web of Science][Medline]
- Manabe K, Ito H, Matsuda H, Noma A, Shibata Y. Classification of ion channels in the luminal and abluminal membranes of guinea-pig endocardial endothelial cells. J Physiol (Lond) (1995) 484:41–52.
[Abstract/Free Full Text] - Hansen AJ, Lund-Andersen H, Crone C. K+-permeability of the blood–brain barrier, investigated by aid of a K+-sensitive microelectrode. Acta Physiol Scand (1977) 101:438–445.[Web of Science][Medline]
- Betz AL, Firth JA, Goldstein GW. Polarity of the blood–brain barrier: distribution of enzymes between the luminal and the abluminal membranes of brain capillary endothelial cells. Brain Res (1980) 192:17–28.[CrossRef][Web of Science][Medline]
- Bannon PG, Kim M-J, Dean RT, Dawes J. Augmentation of vascular endothelial barrier function by heparin and low molecular weight heparin. Thromb Haemost (1995) 73:706–712.[Web of Science][Medline]
- Fransen P, Andries LJ, Van Bedaf D, Demolder M, Sys SU. Cell coupling in cultured endocardial endothelium. Pflug Arch (1996) 431:R323. Abstract.
- Marron K, Wharton J, Sheppard MN, et al. Distribution, morphology, and neurochemistry of endocardial and epicardial nerve terminal arborizations in the human heart. Circulation (1995) 92:2343–2351.
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 A. Adler, H. Huang, Z. Wang, J. Conetta, E. Levee, X. Zhang, and T. H. Hintze Endocardial endothelium in the avascular frog heart: role for diffusion of NO in control of cardiac O2 consumption Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H14 - H21. [Abstract] [Full Text] [PDF]
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 P. Kolh, A. Ghuysen, V. Tchana-Sato, V. D'Orio, P. Gerard, P. Morimont, R. Limet, and B. Lambermont Effects of increased afterload on left ventricular performance and mechanical efficiency are not baroreflex-mediated Eur. J. Cardiothorac. Surg., December 1, 2003; 24(6): 912 - 919. [Abstract] [Full Text] [PDF]
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 S. S. Gerety and D. J. Anderson Cardiovascular ephrinB2 function is essential for embryonic angiogenesis Development, March 5, 2003; 129(6): 1397 - 1410. [Abstract] [Full Text] [PDF]
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 D. L. Brutsaert Cardiac Endothelial-Myocardial Signaling: Its Role in Cardiac Growth, Contractile Performance, and Rhythmicity Physiol Rev, January 1, 2003; 83(1): 59 - 115. [Abstract] [Full Text] [PDF]
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 S. J. Sohn, B. K. Sarvis, D. Cado, and A. Winoto ERK5 MAPK Regulates Embryonic Angiogenesis and Acts as a Hypoxia-sensitive Repressor of Vascular Endothelial Growth Factor Expression J. Biol. Chem., November 1, 2002; 277(45): 43344 - 43351. [Abstract] [Full Text] [PDF]
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M. R. Zile and D. L. Brutsaert New Concepts in Diastolic Dysfunction and Diastolic Heart Failure: Part II: Causal Mechanisms and Treatment Circulation, March 26, 2002; 105(12): 1503 - 1508. [Full Text] [PDF]
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 P. Fransen, J. Hendrickx, D. L Brutsaert, and S. U Sys Distribution and role of Na+/K+ ATPase in endocardial endothelium Cardiovasc Res, December 1, 2001; 52(3): 487 - 499. [Abstract] [Full Text] [PDF]
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R. Rastaldo, N. Paolocci, A. Chiribiri, C. Penna, D. Gattullo, and P. Pagliaro Cytochrome P-450 metabolite of arachidonic acid mediates bradykinin-induced negative inotropic effect Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2823 - H2832. [Abstract] [Full Text] [PDF]
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 S. Ausoni and S. Sartore Cell Lineages and Tissue Boundaries in Cardiac Arterial and Venous Poles : Developmental Patterns, Animal Models, and Implications for Congenital Vascular Diseases Arterioscler Thromb Vasc Biol, March 1, 2001; 21(3): 312 - 320. [Abstract] [Full Text] [PDF]
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S. Z. Kim, K. W. Cho, and S. H. Kim Modulation of endocardial natriuretic peptide receptors in right ventricular hypertrophy Am J Physiol Heart Circ Physiol, December 1, 1999; 277(6): H2280 - H2289. [Abstract] [Full Text] [PDF]
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 E. D. Frohlich The necessity for recognition and treatment of patients with "mild" hypertension J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1369 - 1377. [Abstract] [Full Text] [PDF]
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M. K. Karunanithi, J. A. Young, W. Kalnins, S. Kesteven, and M. P. Feneley Response of the Intact Canine Left Ventricle to Increased Afterload and Increased Coronary Perfusion Pressure in the Presence of Coronary Flow Autoregulation Circulation, October 5, 1999; 100(14): 1562 - 1568. [Abstract] [Full Text] [PDF]
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S. U Sys, G. W De Keulenaer, and D. L Brutsaert Physiopharmacological evaluation of myocardial performance: how to study modulation by cardiac endothelium and related humoral factors? Cardiovasc Res, July 1, 1998; 39(1): 136 - 147. [Full Text] [PDF]
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