title: Angiotensin II type 2 receptor mediates vascular smooth muscle cell apoptosis in cystic medial degeneration associated with Marfan's syndrome.
abstract: BACKGROUND
  Cystic medial degeneration (CMD) is a histological abnormality that is common in the aortic diseases associated with Marfan's syndrome (MFS). Although little known about the mechanism underlying CMD, several recent reports have demonstrated that vascular smooth muscle cell (VSMC) apoptosis could play a substantial role in CMD. On the other hand, angiotensin II (Ang II) has been reported to play an important role in the regulation of VSMC growth and apoptosis via the Ang II type 1 receptor (AT1R) and type 2 receptor (AT2R).
  
  
  RESULTS
  To elucidate the role of Ang II signaling via the Ang II receptors in CMD, we investigated AT1R and AT2R mRNA expression and tissue concentration of Ang II in MFS aortas (n=10) and control aortas (n=12). Furthermore, we examined the effects of an ACE inhibitor, an AT1R blocker, and an AT2R blocker on serum deprivation-induced VSMC apoptosis by organ culture system. AT1R expression was significantly decreased (P<0.01) and AT2R expression was significantly increased (P<0.001) in MFS aortas compared with control aortas, and tissue Ang II concentration was significantly higher in CMD than in the control condition (P<0.01). Both the ACE inhibitor and AT2R blocker significantly inhibited serum deprivation-induced VSMC apoptosis (P<0.05), although the AT1R blocker did not inhibit apoptosis in cultured aortic media from MFS patients.
  
  
  CONCLUSIONS
  Accelerated ACE-dependent Ang II formation and signaling via upregulated AT2R play a pivotal role in VSMC apoptosis in CMD, and the ACE inhibitor could have clinical value in the prevention and treatment of CMD.
authors.affiliation: Department of Cardiology, The Heart Institute of Japan, Second Department of Medicine, Tokyo Women's Medical University, Tokyo, Japan. mnagasih@hij.twmu.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Nagashima
authors.forename: Y
authors.initials: Y
authors.lastname: Sakomura
authors.forename: Y
authors.initials: Y
authors.lastname: Aoka
authors.forename: K
authors.initials: K
authors.lastname: Uto
authors.lastname: Kameyama Ki
authors.forename: M
authors.initials: M
authors.lastname: Ogawa
authors.forename: S
authors.initials: S
authors.lastname: Aomi
authors.forename: H
authors.initials: H
authors.lastname: Koyanagi
authors.forename: N
authors.initials: N
authors.lastname: Ishizuka
authors.forename: M
authors.initials: M
authors.lastname: Naruse
authors.forename: M
authors.initials: M
authors.lastname: Kawana
authors.forename: H
authors.initials: H
authors.lastname: Kasanuki
mesh_terms: D000328:Adult; D000804:Angiotensin II / Q000032:analysis; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001011:Aorta / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008382:Marfan Syndrome / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*; D015398:Signal Transduction; D013841:Thiazepines / Q000494:pharmacology; D017540:Tunica Media / Q000378:metabolism / Q000473:pathology; D018631:ras Proteins / Q000037:antagonists & inhibitors
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D016895:Culture Media, Serum-Free; D007093:Imidazoles; D007211:Indoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013841:Thiazepines; D000804:Angiotensin II; C073402:PD 123319; C069156:temocaprilat; C053500:perindoprilat; D018631:ras Proteins