PMID- 20819950
OWN - NLM
STAT- MEDLINE
DCOM- 20110404
LR  - 20211203
IS  - 1755-3245 (Electronic)
IS  - 0008-6363 (Linking)
VI  - 89
IP  - 1
DP  - 2011 Jan 1
TI  - Angiotensin II blockade: a strategy to slow ageing by protecting mitochondria?
PG  - 31-40
LID - 10.1093/cvr/cvq285 [doi]
AB  - Protein and lipid oxidation-mainly by mitochondrial reactive oxygen species 
      (mtROS)-was proposed as a crucial determinant of health and lifespan. Angiotensin 
      II (Ang II) enhances ROS production by activating NAD(P)H oxidase and uncoupling 
      endothelial nitric oxide synthase (NOS). Ang II also stimulates mtROS production, 
      which depresses mitochondrial energy metabolism. In rodents, renin-angiotensin 
      system blockade (RAS blockade) increases survival and prevents age-associated 
      changes. RAS blockade reduces mtROS and enhances mitochondrial content and 
      function. This suggests that Ang II contributes to the ageing process by 
      prompting mitochondrial dysfunction. Since Ang II is a pleiotropic peptide, the 
      age-protecting effects of RAS blockade are expected to involve a variety of other 
      mechanisms. Caloric restriction (CR)-an age-retarding intervention in humans and 
      animals-and RAS blockade display a number of converging effects, i.e. they delay 
      the manifestations of hypertension, diabetes, nephropathy, cardiovascular 
      disease, and cancer; increase body temperature; reduce body weight, plasma 
      glucose, insulin, and insulin-like growth factor-1; ameliorate insulin 
      sensitivity; lower protein, lipid, and DNA oxidation, and mitochondrial H(2)O(2) 
      production; and increase uncoupling protein-2 and sirtuin expression. A number of 
      these overlapping effects involve changes in mitochondrial function. In CR, 
      peroxisome proliferator-activated receptors (PPARs) seem to contribute to 
      age-retardation partly by regulating mitochondrial function. RAS inhibition 
      up-regulates PPARs; therefore, it is feasible that PPAR modulation is pivotal for 
      mitochondrial protection by RAS blockade during rodent ageing. Other potential 
      mechanisms that may underlie RAS blockade's mitochondrial benefits are TGF-beta 
      down-regulation and up-regulation of Klotho and sirtuins. In conclusion, the 
      available data suggest that RAS blockade deserves further research efforts to 
      establish its role as a potential tool to mitigate the growing problem of 
      age-associated chronic disease.
FAU - de Cavanagh, Elena M V
AU  - de Cavanagh EM
AD  - Center of Hypertension, Cardiology Department, Austral University Hospital, 
      Derqui, Argentina.
FAU - Inserra, Felipe
AU  - Inserra F
FAU - Ferder, Leon
AU  - Ferder L
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20100906
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Oxidants)
RN  - 0 (Peroxisome Proliferator-Activated Receptors)
RN  - 0 (Reactive Oxygen Species)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 3.2.1.31 (Glucuronidase)
RN  - EC 3.2.1.31 (Klotho Proteins)
RN  - EC 3.5.1.- (Sirtuins)
SB  - IM
MH  - Aging/drug effects/genetics/*metabolism
MH  - Angiotensin II/*antagonists & inhibitors
MH  - Angiotensin-Converting Enzyme Inhibitors/pharmacology
MH  - Animals
MH  - Caloric Restriction
MH  - Gene Expression/drug effects
MH  - Glucuronidase/genetics
MH  - Humans
MH  - Klotho Proteins
MH  - Mitochondria/drug effects/*metabolism
MH  - Models, Biological
MH  - Oxidants/metabolism
MH  - Peroxisome Proliferator-Activated Receptors/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Renin-Angiotensin System/drug effects/physiology
MH  - Sirtuins/metabolism
EDAT- 2010/09/08 06:00
MHDA- 2011/04/05 06:00
CRDT- 2010/09/08 06:00
PHST- 2010/09/08 06:00 [entrez]
PHST- 2010/09/08 06:00 [pubmed]
PHST- 2011/04/05 06:00 [medline]
AID - cvq285 [pii]
AID - 10.1093/cvr/cvq285 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2011 Jan 1;89(1):31-40. doi: 10.1093/cvr/cvq285. Epub 2010 Sep 6.