PMID- 20304838
OWN - NLM
STAT- MEDLINE
DCOM- 20110728
LR  - 20100816
IS  - 1522-9645 (Electronic)
IS  - 0195-668X (Linking)
VI  - 31
IP  - 16
DP  - 2010 Aug
TI  - Recombinant apolipoprotein A-I Milano rapidly reverses aortic valve stenosis and 
      decreases leaflet inflammation in an experimental rabbit model.
PG  - 2049-57
LID - 10.1093/eurheartj/ehq064 [doi]
AB  - AIMS: Aortic stenosis (AS) is associated with significant morbidity and 
      mortality. Recombinant apolipoprotein A-I Milano (rApoA-I(M)) induces 
      atherosclerotic plaque regression. The aims of this study were to determine the 
      effects of rApoA-I(M) on experimental aortic valve degeneration and its 
      mechanisms of action. METHODS AND RESULTS: New Zealand White rabbits (n = 20) 
      were fed an atherogenic diet for 9 months and then randomized to either placebo 
      or rApoA-I(M). Echocardiography was used to assess the effect of the treatments 
      on AS. Porcine aortic valve myofibroblasts (PAVMF) treated with oxidized 
      low-density lipoprotein served to define the effects of rApoA-I(M) on the 
      expression of monocyte chemoattractant protein-1 (MCP-1), nuclear factor 
      (NF)-kappaB, and alkaline phosphatase (AP). Recombinant apolipoprotein A-I Milano 
      increased aortic valve area (AVA) by 32% (0.25 +/- 0.05 to 0.34 +/- 0.07 cm(2), P 
      < 0.01); whereas AVA remained unchanged in the placebo group (0.24 +/- 0.05 to 
      0.26 +/- 0.04 cm(2), P = 0.58). Histopathological examination of aortic valves in 
      the rApoA-I(M) animals showed significantly less leaflet thickening, 
      inflammation, and calcification vs. the placebo group. In vitro, rApoA-I(M) 
      significantly inhibited MCP-1, AP, and NF-kappaB and decreased intracellular 
      cholesterol content in PAVMF. CONCLUSION: Recombinant apolipoprotein A-I Milano 
      treatment reverses AS in this experimental rabbit model. The beneficial effects 
      seem to be mediated by enhanced cholesterol removal and by reduced inflammation 
      and calcification.
FAU - Speidl, Walter S
AU  - Speidl WS
AD  - Atherothrombosis Research Unit, Mount Sinai School of Medicine New York, NY, USA.
FAU - Cimmino, Giovanni
AU  - Cimmino G
FAU - Ibanez, Borja
AU  - Ibanez B
FAU - Elmariah, Sammy
AU  - Elmariah S
FAU - Hutter, Randolph
AU  - Hutter R
FAU - Garcia, Mario J
AU  - Garcia MJ
FAU - Fuster, Valentin
AU  - Fuster V
FAU - Goldman, Martin E
AU  - Goldman ME
FAU - Badimon, Juan J
AU  - Badimon JJ
LA  - eng
PT  - Journal Article
DEP - 20100319
PL  - England
TA  - Eur Heart J
JT  - European heart journal
JID - 8006263
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Apolipoprotein A-I)
RN  - 0 (Recombinant Proteins)
RN  - 0 (apolipoprotein A-I Milano)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
SB  - IM
MH  - Alkaline Phosphatase/drug effects
MH  - Animals
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Aortic Valve Stenosis/*drug therapy/pathology
MH  - Apolipoprotein A-I/*therapeutic use
MH  - Calcinosis/pathology
MH  - Myofibroblasts/pathology
MH  - Plaque, Atherosclerotic/pathology
MH  - Rabbits
MH  - Random Allocation
MH  - Recombinant Proteins/therapeutic use
EDAT- 2010/03/23 06:00
MHDA- 2011/07/29 06:00
CRDT- 2010/03/23 06:00
PHST- 2010/03/23 06:00 [entrez]
PHST- 2010/03/23 06:00 [pubmed]
PHST- 2011/07/29 06:00 [medline]
AID - ehq064 [pii]
AID - 10.1093/eurheartj/ehq064 [doi]
PST - ppublish
SO  - Eur Heart J. 2010 Aug;31(16):2049-57. doi: 10.1093/eurheartj/ehq064. Epub 2010 
      Mar 19.