title: Stretch-induced collagen synthesis in cultured smooth muscle cells from rabbit aortic media and a possible involvement of angiotensin II and transforming growth factor-beta.
abstract: Mechanical strain reportedly stimulates the synthesis of collagen in vascular smooth muscle cells (SMCs). The present study was designed to investigate a possible involvement of angiotensin II (Ang II) and transforming growth factor (TGF)-beta in stretch-induced collagen synthesis of cultured SMCs derived from the rabbit aortic media. SMCs were cyclically stretched at a rate of 10% elongation and 30 cycles/min for 24 h using the Flexercell strain unit (Flexcell International Corp., McKeesport, Pa.). A two-fold increase in collagen synthesis and a concurrent increase in total protein synthesis were noted in stretched SMCs. Concentration of immunoreactive Ang II in the conditioned medium was elevated under the mechanical strain. Stretch-induced collagen and total protein synthesis were inhibited by either a selective antagonist to Ang II (saralasin), an angiotensin I-converting enzyme inhibitor (captopril) or an antisense oligonucleotide for angiotensinogen mRNA. An elevated secretion of TGF-beta, both active and latent forms, was found in the medium of stretched SMCs. Saralasin inhibited the stretch-induced secretion of TGF-beta from SMCs. Stretch-induced collagen and total protein synthesis was further inhibited by either an anti-TGF-beta1 neutralizing antibody or an adenovirus-mediated transfer of a truncated TGF-beta type II receptor. Elevated expression of collagen alpha1(III) chain and TGF-beta1 mRNAs, and its reversal by saralasin were also demonstrated in stretched SMCs. Results indicate that the stretch-induced collagen and total protein synthesis appears to be mediated via an autocrine-paracrine mechanism of Ang II and TGF-beta released from SMCs.
authors.affiliation: First Department of Pathology, Wakayama Medical College, Japan.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Muragaki
authors.forename: I
authors.initials: I
authors.lastname: Hatamura
authors.forename: H
authors.initials: H
authors.lastname: Ueno
authors.forename: A
authors.initials: A
authors.lastname: Ooshima
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D005470:Fluorometry; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D013314:Stress, Mechanical; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D017540:Tunica Media / Q000166:cytology / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D009124:Muscle Proteins; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D000808:Angiotensinogen; D000804:Angiotensin II; D003094:Collagen