PMID- 19375241
OWN - NLM
STAT- MEDLINE
DCOM- 20090805
LR  - 20211203
IS  - 1532-2777 (Electronic)
IS  - 0306-9877 (Linking)
VI  - 73
IP  - 2
DP  - 2009 Aug
TI  - Everolimus, a promising medical therapy for coronary heart disease?
PG  - 153-5
LID - 10.1016/j.mehy.2009.03.011 [doi]
AB  - Coronary heart disease is mainly caused by atherosclerosis, which is a 
      multifactorial and systemic disease. Lipid metabolism disorder and chronic 
      inflammation are two well accepted mechanisms leading to atherosclerosis. The key 
      initiating process in athrogenesis is lipid retention in subendothelium. 
      Inflammatory activity plays an important role in the whole pathogenesis of 
      atherosclerosis. Recent investigations have demonstrated that rapamycin reduces 
      lipid retention by increasing adipose-tissue lipase activity and decreasing 
      lipoprotein lipase activity. Rapamycin also reduce intracellular lipid 
      accumulation in smooth muscle cells and macrophages. Since rapamycin is a 
      definite immunosuppressive agent, and inflammatory process has been involved in 
      atherosclerosis, the compound would have effect on the progression of 
      atherosclerosis through reducing inflammatory activity. Moreover, rapamycin would 
      protect plaque from rupture by selectively clearing macrophages without affecting 
      vascular smooth muscle cells. Even some in vivo studies demonstrate that 
      rapamycin can notably inhibit the development of atherosclerosis. Rapamycin, 
      especially its analog, everolimus, is a non-toxic, well-tolerated drug suitable 
      for long term use. Clinical experiments demonstrate that everolimus can reduce 
      graft vasculopathy in heart transplant patients. Therefore, we propose that 
      everolimus administered systemically is a promising medical therapy to attenuate 
      atherosclerosis and prevent further adverse events. In addition, rapamycin is a 
      selective and effective mammalian target of rapamycin (mTOR) inhibitor. mTOR acts 
      as a hub for cell metabolism, cell growth and cell survival. Based on previous 
      evidences, we hypotheses that mTOR signaling pathway could play a significant 
      role in the pathogenesis of atherosclerosis.
FAU - Jia, Lei
AU  - Jia L
AD  - Hypertension Division, Fuwai Hospital and Cardiovascular Institute, 167 
      Beilishilu, Beijing 100037, PR China.
FAU - Hui, Ru-Tai
AU  - Hui RT
LA  - eng
PT  - Journal Article
DEP - 20090416
PL  - United States
TA  - Med Hypotheses
JT  - Medical hypotheses
JID - 7505668
RN  - 0 (Immunosuppressive Agents)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Coronary Disease/*drug therapy
MH  - Everolimus
MH  - Humans
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Protein Kinases/metabolism
MH  - Signal Transduction
MH  - Sirolimus/*analogs & derivatives/therapeutic use
MH  - TOR Serine-Threonine Kinases
EDAT- 2009/04/21 09:00
MHDA- 2009/08/06 09:00
CRDT- 2009/04/21 09:00
PHST- 2009/02/26 00:00 [received]
PHST- 2009/02/26 00:00 [revised]
PHST- 2009/03/05 00:00 [accepted]
PHST- 2009/04/21 09:00 [entrez]
PHST- 2009/04/21 09:00 [pubmed]
PHST- 2009/08/06 09:00 [medline]
AID - S0306-9877(09)00195-9 [pii]
AID - 10.1016/j.mehy.2009.03.011 [doi]
PST - ppublish
SO  - Med Hypotheses. 2009 Aug;73(2):153-5. doi: 10.1016/j.mehy.2009.03.011. Epub 2009 
      Apr 16.