PMID- 12166897
OWN - NLM
STAT- MEDLINE
DCOM- 20030116
LR  - 20151119
IS  - 0344-0338 (Print)
IS  - 0344-0338 (Linking)
VI  - 198
IP  - 6
DP  - 2002
TI  - Immunohistochemical study of endothelin-1 and matrix metalloproteinases in 
      plexogenic pulmonary arteriopathy.
PG  - 403-12
AB  - The matrix metalloproteinases (MMPs) and endothelin-1, a potent vasoconstrictor 
      and mitogen for smooth muscle cells, have been shown to be involved in the 
      pathogenesis of various vascular disorders. However, the expression of 
      endothelin-1 and the activation of MMPs have not been fully evaluated in 
      plexogenic pulmonary arteriopathy (PPA). Immunohistochemical and confocal 
      microscopic studies were conducted to evaluate the reactivity of lung tissue from 
      six patients with pulmonary hypertension for alpha-smooth muscle actin 
      (alpha-SMA), desmin, vimentin, factor VIII, endothelin-1, various types of MMPs 
      (MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9), membrane type-MMPs (MT-MMPs), tissue 
      inhibitors of MMPs (TIMPs), and type IV collagen. Four major arterial 
      morphological abnormalities were recognized in PPA: muscularization of pulmonary 
      arterioles, onion-skin lesions, cellular and mature plexiform lesions, and 
      atheromas in elastic pulmonary arteries. Reactivity for MMP-2 and MT-1-MMP was 
      found in endothelial cells and, to a lesser extent, in myofibroblasts 
      proliferating in various lesions of PPA. Increased expression of endothelin-1 was 
      observed in the latter cells and in endothelial cells. Some myofibroblasts were 
      positive for MMP-3 and MMP-7 in the vascular lesions except for mature plexiform 
      lesions. MMP-1, MMP-9 and TIMP-2 tended to be positive only in the atheromatous 
      lesions. Staining for type IV collagen showed focal thinning and discontinuities 
      of the endothelial basement membrane in plexiform lesions. This study 
      demonstrates colocalization of MMP-2 with MT-1-MMP and increased expression of 
      endothelin-1 in various arterial lesions of PPA. These changes may play important 
      roles in the remodeling of arterial structures, particularly of basement 
      membranes, in this disorder.
FAU - Matsui, Kazuhiro
AU  - Matsui K
AD  - Department of Pathology, Faculty of Medicine, Toyama Medical and Pharmaceutical 
      University, Japan. kmp@ms.toyama-mpu.ac.jp
FAU - Takano, Yasuo
AU  - Takano Y
FAU - Yu, Zu-Xi
AU  - Yu ZX
FAU - Hi, Joanne Eunhee Suh
AU  - Hi JE
FAU - Stetler-Stevenson, William G
AU  - Stetler-Stevenson WG
FAU - Travis, William D
AU  - Travis WD
FAU - Ferrans, Victor J
AU  - Ferrans VJ
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Germany
TA  - Pathol Res Pract
JT  - Pathology, research and practice
JID - 7806109
RN  - 0 (Biomarkers)
RN  - 0 (Collagen Type IV)
RN  - 0 (Endothelin-1)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Biomarkers/analysis
MH  - Collagen Type IV/metabolism
MH  - Endothelin-1/*metabolism
MH  - Female
MH  - Humans
MH  - Hypertension, Pulmonary/complications/*metabolism/pathology
MH  - Immunohistochemistry
MH  - Male
MH  - Matrix Metalloproteinases/*metabolism
MH  - Microscopy, Confocal
MH  - Middle Aged
MH  - Peripheral Vascular Diseases/etiology/*metabolism/pathology
MH  - Pulmonary Alveoli/pathology
MH  - Pulmonary Artery/*metabolism/pathology
EDAT- 2002/08/09 10:00
MHDA- 2003/01/17 04:00
CRDT- 2002/08/09 10:00
PHST- 2002/08/09 10:00 [pubmed]
PHST- 2003/01/17 04:00 [medline]
PHST- 2002/08/09 10:00 [entrez]
AID - S0344-0338(04)70272-1 [pii]
AID - 10.1078/0344-0338-00273 [doi]
PST - ppublish
SO  - Pathol Res Pract. 2002;198(6):403-12. doi: 10.1078/0344-0338-00273.