Mechanisms of apoptosis after ischemia and reperfusion: Role of the renin-angiotensin system

Abstract Background: Apoptosis plays a key role in the pathogenesis of cardiac diseases. We examined the influence of the renin-angiotensin system (RAS) on different regulators of apoptosis using an isolated hemoperfused working porcine heart model of acute ischemia (2 h), followed by reperfusion (4 h). Methods and Results: 23 porcine hearts were randomized to 5 groups: hemoperfused non-infarcted hearts (C), infarcted hearts (MI: R. circumflexus), infarcted hearts treated with quinaprilat (Q), infarcted hearts treated with angiotensin-I (Ang I), and infarcted hearts treated with angiotensin-I and quinaprilat (QA). Fas, Bax, bcl-2 and p53 proteins were increased in MI hearts and further elevated by Ang I. Quinaprilat reduced Bax and p53. Bcl-2 was elevated in Q and reduced in QA. An early upregulation of caspase-3 gene and protein expression was detected in MI and Ang I hearts compared to C. Q reduced caspase-3 gene expression, but had no effect on caspase-3 and Fas protein. Conclusions: These data suggest that the RAS plays a pivotal role in cardiac apoptosis which is the early and predominant form of death in myocardial infarction. Ischemia/reperfusion induces programmed cell death via extrinsic and intrinsic pathways. Early treatment with quinaprilat attenuated cardiomyocyte apoptosis..

Medienart:

E-Artikel

Erscheinungsjahr:

2006

Erschienen:

2006

Enthalten in:

Zur Gesamtaufnahme - volume:11

Enthalten in:

Apoptosis - 11(2006), 3 vom: März, Seite 347-358

Sprache:

Englisch

Beteiligte Personen:

Kossmehl, P. [VerfasserIn]
Kurth, E. [VerfasserIn]
Faramarzi, S. [VerfasserIn]
Habighorst, B. [VerfasserIn]
Shakibaei, M. [VerfasserIn]
Wehland, M. [VerfasserIn]
Kreutz, R. [VerfasserIn]
Infanger, M. [VerfasserIn]
J. Danser, A. H. [VerfasserIn]
Grosse, J. [VerfasserIn]
Paul, M. [VerfasserIn]
Grimm, D. [VerfasserIn]

Links:

Volltext [lizenzpflichtig]

BKL:

44.00$jMedizin: Allgemeines

Themen:

ACE-inhibition
Apoptosis
Fas
Myocardial infarction
P53

RVK:

RVK Klassifikation

Anmerkungen:

© Springer Science + Business Media, Inc. 2006

doi:

10.1007/s10495-006-4350-9

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC2111321311