Differential response of cardiac fibroblasts from young adult and senescent rats to ANG II.
The intracardiac ANG II-forming pathway is activated in the senescent myocardium, raising the possibility of enhanced ANG II effects on cardiac fibroblasts. This study established an in vitro model of cultured cardiac fibroblasts from aged rats to examine if the response of these cells to ANG II is modified in the aged heart. Levels of mRNA encoding renin, angiotensinogen, and the AT(1) receptor subtype in cardiac fibroblasts from young adult and senescent rats were quantified by RT-PCR, net collagen production by a hydroxyproline-based assay, and transforming growth factor (TGF)-beta levels using a commercial kit. In cardiac fibroblasts from young adult rats, ANG II significantly enhanced AT(1) mRNA levels, net collagen production, and TGF-beta production. In fibroblasts from the aged myocardium, ANG II downregulated AT(1) mRNA expression, had a less pronounced effect on net collagen production, and had no effect on TGF-beta production. Such age-related modification of the response of cardiac fibroblasts to ANG II may counteract the effects of augmented intracardiac ANG II production in the senescent heart, limiting fibrogenesis.
Shivakumar
K
K
Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. shivak@sctimst.ker.nic.in
Dostal
David E
DE
Boheler
Kenneth
K
Baker
Kenneth M
KM
Lakatta
Edward G
EG
D000375:Aging; D000804:Angiotensin II / Q000494:pharmacology*; D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000166:cytology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000235:genetics; D012083:Renin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D016212:Transforming Growth Factor beta; D000808:Angiotensinogen; D000804:Angiotensin II; D003094:Collagen; D012083:Renin