Human brain microvessel endothelial cell culture as a model system to study vascular factors of ischemic brain

Zoltán Nagy, Mónika Vastag, Judit Skopál, K. Kolev, R. Machovich, J. Krámer, I. Karádi, Miklós Tóth

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Cerebral ischemia is caused by reduced blood supply at the microcirculatory level. In the microvessels, the main elements of the reperfusion injury following brain ischemia are the transformation of endothelial cell-surface from anticoagulant to procoagulant property, leukocyte adhesion, sludge or clot formation. There is a paucity of information on how hemostatic factors, cytokines, lipoprotein(a) (Lp(a)) and endothelin-1 (ET-1), being responsible for ischemic/reperfusion injury, interact with human brain microvessel endothelium (HBEC). There are no data furthermore about the expression of complement proteins of HBEC influenced by cytokines or fibrinolytic factors. Previously we established optimal conditions for culturing HBEC. Cell contraction induced by thrombin, plasmin, miniplasmin was recorded. The reassembly of F-actin was observed after thrombin treatment. ICAM-1 upregulation was measured following TNF-α, DL-1-α and thrombin incubation. Plasmin and miniplasmin downregulated the ICAM-1 in our cell culture system. Lp(a) modulated the thromboresistant cell-surface by reduction of t-PA and u-PA, but PAI-1 remained unchanged. Lp(a) modulated the ET-1 production by early increasing and late decreasing, in a bimodal manner. The increased secretion of ET-1 by cytokines (TNF-α, IL-1-α) was reduced in the presence of Lp(a). Gradual increase of complement proteins (factor H, factor B, C4) was induced by cytokines. Plasmin and miniplasmin augmented a rapid increase of C4. Some factors of complex relationship between regulators and modulators of endothelial adhesion molecules have been demonstrated in a human cell culture system prepared from brain microvessel endothelium. A unified concept of sequential events of ischemia/reperfusion in the brain has not yet developed.

Original languageEnglish
Pages (from-to)200-206
Number of pages7
JournalKeio Journal of Medicine
Volume45
Issue number3
Publication statusPublished - Sep 1996

Fingerprint

Lipoprotein(a)
Microvessels
Fibrinolysin
Endothelin-1
Endothelial Cells
Cell Culture Techniques
Thrombin
Cytokines
Brain
Intercellular Adhesion Molecule-1
Reperfusion Injury
Brain Ischemia
Endothelium
Complement System Proteins
Complement Factor H
Complement Factor B
Plasminogen Activator Inhibitor 1
Hemostatics
Sewage
Interleukin-1

Keywords

  • Complement proteins
  • ET-1
  • Human brain endothelium
  • ICAM-1
  • Lp(a)

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Human brain microvessel endothelial cell culture as a model system to study vascular factors of ischemic brain. / Nagy, Zoltán; Vastag, Mónika; Skopál, Judit; Kolev, K.; Machovich, R.; Krámer, J.; Karádi, I.; Tóth, Miklós.

In: Keio Journal of Medicine, Vol. 45, No. 3, 09.1996, p. 200-206.

Research output: Contribution to journalArticle

@article{a9109f6ef3fa45cc814e62d56ae4024d,
title = "Human brain microvessel endothelial cell culture as a model system to study vascular factors of ischemic brain",
abstract = "Cerebral ischemia is caused by reduced blood supply at the microcirculatory level. In the microvessels, the main elements of the reperfusion injury following brain ischemia are the transformation of endothelial cell-surface from anticoagulant to procoagulant property, leukocyte adhesion, sludge or clot formation. There is a paucity of information on how hemostatic factors, cytokines, lipoprotein(a) (Lp(a)) and endothelin-1 (ET-1), being responsible for ischemic/reperfusion injury, interact with human brain microvessel endothelium (HBEC). There are no data furthermore about the expression of complement proteins of HBEC influenced by cytokines or fibrinolytic factors. Previously we established optimal conditions for culturing HBEC. Cell contraction induced by thrombin, plasmin, miniplasmin was recorded. The reassembly of F-actin was observed after thrombin treatment. ICAM-1 upregulation was measured following TNF-α, DL-1-α and thrombin incubation. Plasmin and miniplasmin downregulated the ICAM-1 in our cell culture system. Lp(a) modulated the thromboresistant cell-surface by reduction of t-PA and u-PA, but PAI-1 remained unchanged. Lp(a) modulated the ET-1 production by early increasing and late decreasing, in a bimodal manner. The increased secretion of ET-1 by cytokines (TNF-α, IL-1-α) was reduced in the presence of Lp(a). Gradual increase of complement proteins (factor H, factor B, C4) was induced by cytokines. Plasmin and miniplasmin augmented a rapid increase of C4. Some factors of complex relationship between regulators and modulators of endothelial adhesion molecules have been demonstrated in a human cell culture system prepared from brain microvessel endothelium. A unified concept of sequential events of ischemia/reperfusion in the brain has not yet developed.",
keywords = "Complement proteins, ET-1, Human brain endothelium, ICAM-1, Lp(a)",
author = "Zolt{\'a}n Nagy and M{\'o}nika Vastag and Judit Skop{\'a}l and K. Kolev and R. Machovich and J. Kr{\'a}mer and I. Kar{\'a}di and Mikl{\'o}s T{\'o}th",
year = "1996",
month = "9",
language = "English",
volume = "45",
pages = "200--206",
journal = "Keio Journal of Medicine",
issn = "0022-9717",
publisher = "Keio University School of Medicine",
number = "3",

}

TY - JOUR

T1 - Human brain microvessel endothelial cell culture as a model system to study vascular factors of ischemic brain

AU - Nagy, Zoltán

AU - Vastag, Mónika

AU - Skopál, Judit

AU - Kolev, K.

AU - Machovich, R.

AU - Krámer, J.

AU - Karádi, I.

AU - Tóth, Miklós

PY - 1996/9

Y1 - 1996/9

N2 - Cerebral ischemia is caused by reduced blood supply at the microcirculatory level. In the microvessels, the main elements of the reperfusion injury following brain ischemia are the transformation of endothelial cell-surface from anticoagulant to procoagulant property, leukocyte adhesion, sludge or clot formation. There is a paucity of information on how hemostatic factors, cytokines, lipoprotein(a) (Lp(a)) and endothelin-1 (ET-1), being responsible for ischemic/reperfusion injury, interact with human brain microvessel endothelium (HBEC). There are no data furthermore about the expression of complement proteins of HBEC influenced by cytokines or fibrinolytic factors. Previously we established optimal conditions for culturing HBEC. Cell contraction induced by thrombin, plasmin, miniplasmin was recorded. The reassembly of F-actin was observed after thrombin treatment. ICAM-1 upregulation was measured following TNF-α, DL-1-α and thrombin incubation. Plasmin and miniplasmin downregulated the ICAM-1 in our cell culture system. Lp(a) modulated the thromboresistant cell-surface by reduction of t-PA and u-PA, but PAI-1 remained unchanged. Lp(a) modulated the ET-1 production by early increasing and late decreasing, in a bimodal manner. The increased secretion of ET-1 by cytokines (TNF-α, IL-1-α) was reduced in the presence of Lp(a). Gradual increase of complement proteins (factor H, factor B, C4) was induced by cytokines. Plasmin and miniplasmin augmented a rapid increase of C4. Some factors of complex relationship between regulators and modulators of endothelial adhesion molecules have been demonstrated in a human cell culture system prepared from brain microvessel endothelium. A unified concept of sequential events of ischemia/reperfusion in the brain has not yet developed.

AB - Cerebral ischemia is caused by reduced blood supply at the microcirculatory level. In the microvessels, the main elements of the reperfusion injury following brain ischemia are the transformation of endothelial cell-surface from anticoagulant to procoagulant property, leukocyte adhesion, sludge or clot formation. There is a paucity of information on how hemostatic factors, cytokines, lipoprotein(a) (Lp(a)) and endothelin-1 (ET-1), being responsible for ischemic/reperfusion injury, interact with human brain microvessel endothelium (HBEC). There are no data furthermore about the expression of complement proteins of HBEC influenced by cytokines or fibrinolytic factors. Previously we established optimal conditions for culturing HBEC. Cell contraction induced by thrombin, plasmin, miniplasmin was recorded. The reassembly of F-actin was observed after thrombin treatment. ICAM-1 upregulation was measured following TNF-α, DL-1-α and thrombin incubation. Plasmin and miniplasmin downregulated the ICAM-1 in our cell culture system. Lp(a) modulated the thromboresistant cell-surface by reduction of t-PA and u-PA, but PAI-1 remained unchanged. Lp(a) modulated the ET-1 production by early increasing and late decreasing, in a bimodal manner. The increased secretion of ET-1 by cytokines (TNF-α, IL-1-α) was reduced in the presence of Lp(a). Gradual increase of complement proteins (factor H, factor B, C4) was induced by cytokines. Plasmin and miniplasmin augmented a rapid increase of C4. Some factors of complex relationship between regulators and modulators of endothelial adhesion molecules have been demonstrated in a human cell culture system prepared from brain microvessel endothelium. A unified concept of sequential events of ischemia/reperfusion in the brain has not yet developed.

KW - Complement proteins

KW - ET-1

KW - Human brain endothelium

KW - ICAM-1

KW - Lp(a)

UR - http://www.scopus.com/inward/record.url?scp=0030239093&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030239093&partnerID=8YFLogxK

M3 - Article

C2 - 8897762

AN - SCOPUS:0030239093

VL - 45

SP - 200

EP - 206

JO - Keio Journal of Medicine

JF - Keio Journal of Medicine

SN - 0022-9717

IS - 3

ER -