Polymorphism in gene coding for ACE determines different development of myocardial fibrosis in rats

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dc.contributor.authorOcaranza, MP
dc.contributor.authorDiaz Araya, G
dc.contributor.authorCarreno, JE
dc.contributor.authorMunoz, D
dc.contributor.authorRiveros, JP
dc.contributor.authorJalil, JE
dc.contributor.authorLavandero, S
dc.date.accessioned2024-01-10T12:41:35Z
dc.date.available2024-01-10T12:41:35Z
dc.date.issued2004
dc.description.abstractIn humans, the effect of angiotensin-converting enzyme (ACE) gene polymorphisms in cardiovascular disease is still controversial. In the rat, a microsatellite marker in the ACE gene allows differentiation of the ACE gene polymorphism among strains with different ACE levels. We tested the hypothesis that this ACE gene polymorphism determines the extent of cardiac fibrosis induced by isoproterenol (Iso) in the rat. We used a male F-2 generation (homozygous LL and BB ACE genotypes determined by polymerase chain reaction) derived from two rat strains [Brown-Norway (BB) and Lewis (LL)] that differ with respect to their plasma ACE activities. For induction of left ventricular (LV) hypertrophy (LVH) and cardiac fibrosis, rats were infused with Iso (5 mg.kg(-1).day(-1)) or saline (control) for 10 days and euthanized at day 1 after the last injection. The interstitial collagen volumetric fraction (ICVF), collagen I, and fibronectin content, but not collagen III content, were significantly higher in the homozygous BB rats than in homozygous LL rats. Differences in metalloprotease (MMP)-9, but not in MMP-2 activities as well as in cardiac cell proliferation, were also detected between LL and BB rats treated with Iso. LV ACE activity was higher in BB rats than LL rats and correlated with ICVF (r=0.61, P<0.002). No changes were observed in plasma ACE activities, ANG II plasma or LV levels, plasma renin activity, and ACE and ANG II type 1 receptor (AT1R) mRNA levels in the LV of rats with the two different ACE polymorphisms. Iso induced a similar degree of LVH [assessed by an increase in LV weight 100 per body weight, LV-to-right ventricle (RV) ratio, and LV protein content] in LL and BB rats. We concluded that rats in the F-2 generation with high plasma ACE activity developed more fibrosis but to a similar degree of LVH compared with rats with low plasma ACE activity.
dc.fechaingreso.objetodigital2024-05-14
dc.format.extent9 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1152/ajpheart.00102.2003
dc.identifier.eissn1522-1539
dc.identifier.issn0363-6135
dc.identifier.pubmedidMEDLINE:14527934
dc.identifier.urihttps://doi.org/10.1152/ajpheart.00102.2003
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/77431
dc.identifier.wosidWOS:000187911900004
dc.information.autorucMedicina;Jalil J;S/I;99946
dc.information.autorucMedicina;Ocaranza M;S/I;1001254
dc.issue.numero2
dc.language.isoen
dc.nota.accesocontenido parcial
dc.publisherAMER PHYSIOLOGICAL SOC
dc.revistaAMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
dc.rightsacceso restringido
dc.subjectrenin angiotensin system
dc.subjectfibrosis
dc.subjecthypertrophy
dc.subjectangiotensin-converting enzyme
dc.subjectangiotensin-converting enzyme gene polymorphism
dc.subjectANGIOTENSIN-CONVERTING-ENZYME
dc.subjectCONGESTIVE-HEART-FAILURE
dc.subjectMATRIX METALLOPROTEINASES
dc.subjectCARDIAC-HYPERTROPHY
dc.subjectCARDIOVASCULAR-DISEASE
dc.subjectDELETION POLYMORPHISM
dc.subjectPLASMA NOREPINEPHRINE
dc.subjectALDOSTERONE SYSTEM
dc.subjectLEFT-VENTRICLE
dc.subjectHYPERTENSION
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titlePolymorphism in gene coding for ACE determines different development of myocardial fibrosis in rats
dc.typeartículo
dc.volumen286
sipa.codpersvinculados99946
sipa.codpersvinculados1001254
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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