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Structure and function of cardiovascular endothelium
J Mol
L4
Cell
Cardiol
HYPERTROPHY
21 (Supplement
IV) (1989)
AND HEART FAILURE.
H.-G.Zimmer,
Dept.Physiol.
University
Munich,
F.R.G.
When the load imposed on the myocardium is too high or when cardiac hypertrophy lasts for longer periods of time, the heart may develop failure. To examine these aspects, two experimental in viva rat models were studied: 1. Acute left ventricular (LV) failure was induced by simultaneous constriction of the abdominal aorta and administration of the B-adrenergic agonist isoproterenol. After 24 hours (Science 220, 81, 1983), LVSP (nun Hg) was reduced from 142 _t 4 (n=lY) to 111 2 5 (n=ll) and the pres sure-rate-product (mm Hg/min) from 58342 f 1897 to 34764 '+ 4600. The ATP content (pmoles/g) had declined from 4.4 r 0.01 (n=30) to 3.4 + 0.1 (n=14). Concomitant i.v. infusion of ribose (200 mg/kg/h) for 24 hours normalized both the functional and metabolic alterations. Thus, restoration of the ATP pool had a beneficial effect on global heart function. 2. Chronic LV failure was produced by LAD coronary artery ligation. After 4 weeks, LVSP (mm Hg) was reduced from 154 + 3 (n=20) to 115 + 3 (n=l5), cardiac output (ml/kg/min) from 352 + 12 to 270 '+ 14. LVEDP (mm Hg) was markedly elevated from 3.4 + 0.8 to 32 + 2. Cells isolated from the noninfarcted LV and septum (Circulation 78, 11-648, 2583, 1988) were elongated by 15%. The septum had a 23% higher weight. These results indicate that the LV and septum had developed moderate hypertrophy and were dilated most probably due to an increase in LV enddiastolic volume. Supported
L5
by
the
Deutsche
Forschungsgemeinschaft
(Zi
199/4-S).
STRUCTURE AND PUNCTION OF CARDIOVASCULAR BNDOTHELIUM. W. Schaper, Max-Planck-Institute, Department of Experimental Cardiology, Bad Nauheim, PR Germany. Ultrastructurally. the endothelium of small vessels in the heart is characterized by numerous pinocytotic vesicles, few mitochondria, Weibel-Palade-bodies (mainly in the human heart), and stress fibers (-actin) on the abluminal side. Endothelium stains with antibodies against vinculin, vimentin and actin, but not with desmin. UEAI stains only with human endoSpecies variation exists in the binding of lectins: thelial cells. Other typical markers for endothelial cells are: alkaline phosphatase, nucleoside phosphorylase, and 5’-nucleotidase, the LDL-receptor and Factor VIII-antigen (not in the pig). Porcine aortic endothelial cells (in contrast to bovine cells) do not express adenosine deaminase and xanthine oxidase. Bndothelial cells in culture After only few passages degenerative change shape but retain the typical markers. changes are visible but only ultrastructurally (myelin-figures). We have studied the rate of reproduction of bovine and porcine aortic endothelial cells in culture and calf serum) and to antheir response to growth factors (acidic and basic FGF; fetal horse-serum, tiesue extracts). Inhibitors of nucleoside timitogens (interferons, transport significantly inhibit the uptake of tritiated thymidine but do not interfere with cell proliferation. Bndothelium (in situ) is much more tolerant toward ischemia than myocytes.
L6
ENDOTHELIUM AND FIBRINOLYSIS. D. Collen. Center for Thrombosis and VascularResearch, University of Leuven, Belgium. Endothelium plays an important role in the regulation of fibrinolysis via the production of both plasminogen activators (mainly tissue-type, t-PA, but also urokinase-type, u-PA) and plasminogen activator inhibitors (mainly PAIbut also PAI-2). The synthesis and secretion of these proteins are highly regulated. PA production is dependent on the vascular origin of the cells, and may be stimulated by thrombin, histamine, butyrate, phorbol esters, retinoic acid, etc. Additional regulatory mechanisms include conversion of single chain u-PA to more active two chain u-PA, and interactions with cellular receptors and with circulating and SWface-bound inhibitors. The synthesis of PAIis highly regulated and modulated by such compounds as endotoxin, thrombin, transforming growth factor R, tumor necrosis factor biological and pharmacological studies are and interleukin 1. Molecular beginning to elucidate these regulatory mechanisms. However, to date no pharmacological compounds have been identified which would specifically upregulate PA synthesis or downregulate PA1 synthesis, which would allow to tip the balance between the procoagulant and profibrinolytic pathways in blood towards a less prethrombotic state. s.2
L4
Cell
Cardiol
HYPERTROPHY
21 (Supplement
IV) (1989)
AND HEART FAILURE.
H.-G.Zimmer,
Dept.Physiol.
University
Munich,
F.R.G.
When the load imposed on the myocardium is too high or when cardiac hypertrophy lasts for longer periods of time, the heart may develop failure. To examine these aspects, two experimental in viva rat models were studied: 1. Acute left ventricular (LV) failure was induced by simultaneous constriction of the abdominal aorta and administration of the B-adrenergic agonist isoproterenol. After 24 hours (Science 220, 81, 1983), LVSP (nun Hg) was reduced from 142 _t 4 (n=lY) to 111 2 5 (n=ll) and the pres sure-rate-product (mm Hg/min) from 58342 f 1897 to 34764 '+ 4600. The ATP content (pmoles/g) had declined from 4.4 r 0.01 (n=30) to 3.4 + 0.1 (n=14). Concomitant i.v. infusion of ribose (200 mg/kg/h) for 24 hours normalized both the functional and metabolic alterations. Thus, restoration of the ATP pool had a beneficial effect on global heart function. 2. Chronic LV failure was produced by LAD coronary artery ligation. After 4 weeks, LVSP (mm Hg) was reduced from 154 + 3 (n=20) to 115 + 3 (n=l5), cardiac output (ml/kg/min) from 352 + 12 to 270 '+ 14. LVEDP (mm Hg) was markedly elevated from 3.4 + 0.8 to 32 + 2. Cells isolated from the noninfarcted LV and septum (Circulation 78, 11-648, 2583, 1988) were elongated by 15%. The septum had a 23% higher weight. These results indicate that the LV and septum had developed moderate hypertrophy and were dilated most probably due to an increase in LV enddiastolic volume. Supported
L5
by
the
Deutsche
Forschungsgemeinschaft
(Zi
199/4-S).
STRUCTURE AND PUNCTION OF CARDIOVASCULAR BNDOTHELIUM. W. Schaper, Max-Planck-Institute, Department of Experimental Cardiology, Bad Nauheim, PR Germany. Ultrastructurally. the endothelium of small vessels in the heart is characterized by numerous pinocytotic vesicles, few mitochondria, Weibel-Palade-bodies (mainly in the human heart), and stress fibers (-actin) on the abluminal side. Endothelium stains with antibodies against vinculin, vimentin and actin, but not with desmin. UEAI stains only with human endoSpecies variation exists in the binding of lectins: thelial cells. Other typical markers for endothelial cells are: alkaline phosphatase, nucleoside phosphorylase, and 5’-nucleotidase, the LDL-receptor and Factor VIII-antigen (not in the pig). Porcine aortic endothelial cells (in contrast to bovine cells) do not express adenosine deaminase and xanthine oxidase. Bndothelial cells in culture After only few passages degenerative change shape but retain the typical markers. changes are visible but only ultrastructurally (myelin-figures). We have studied the rate of reproduction of bovine and porcine aortic endothelial cells in culture and calf serum) and to antheir response to growth factors (acidic and basic FGF; fetal horse-serum, tiesue extracts). Inhibitors of nucleoside timitogens (interferons, transport significantly inhibit the uptake of tritiated thymidine but do not interfere with cell proliferation. Bndothelium (in situ) is much more tolerant toward ischemia than myocytes.
L6
ENDOTHELIUM AND FIBRINOLYSIS. D. Collen. Center for Thrombosis and VascularResearch, University of Leuven, Belgium. Endothelium plays an important role in the regulation of fibrinolysis via the production of both plasminogen activators (mainly tissue-type, t-PA, but also urokinase-type, u-PA) and plasminogen activator inhibitors (mainly PAIbut also PAI-2). The synthesis and secretion of these proteins are highly regulated. PA production is dependent on the vascular origin of the cells, and may be stimulated by thrombin, histamine, butyrate, phorbol esters, retinoic acid, etc. Additional regulatory mechanisms include conversion of single chain u-PA to more active two chain u-PA, and interactions with cellular receptors and with circulating and SWface-bound inhibitors. The synthesis of PAIis highly regulated and modulated by such compounds as endotoxin, thrombin, transforming growth factor R, tumor necrosis factor biological and pharmacological studies are and interleukin 1. Molecular beginning to elucidate these regulatory mechanisms. However, to date no pharmacological compounds have been identified which would specifically upregulate PA synthesis or downregulate PA1 synthesis, which would allow to tip the balance between the procoagulant and profibrinolytic pathways in blood towards a less prethrombotic state. s.2