PMID- 29685053
OWN - NLM
STAT- MEDLINE
DCOM- 20190624
LR  - 20211204
IS  - 1940-4034 (Electronic)
IS  - 1074-2484 (Linking)
VI  - 23
IP  - 5
DP  - 2018 Sep
TI  - Cardioprotective and Anti-Aggregatory Effects of Levosimendan on 
      Isoproterenol-Induced Myocardial Injury in High-Fat-Fed Rats Involves Modulation 
      of PI3K/Akt/mTOR Signaling Pathway and Inhibition of Apoptosis: Comparison to 
      Cilostazol.
PG  - 456-471
LID - 10.1177/1074248418763957 [doi]
AB  - Hyperlipidemia and hypercoagulability states are linked with the increased risks 
      of myocardial infarction (MI). Levosimendan has vasorelaxant and anti-aggregatory 
      properties. The present study evaluated the anti-aggregatory and cardioprotective 
      effects of levosimendan versus cilostazol in high-fat diet (HFD)-fed rats 
      subjected to isoproterenol-induced MI. Rats were assigned to normal, HFD, HFD + 
      isoproterenol, HFD + isoproterenol + cilostazol, and HFD + isoproterenol + 
      levosimendan. The present study investigated the anti-aggregatory effect of both 
      levosimendan and cilostazol and revealed that both drugs attenuated the severity 
      of platelet aggregation. Moreover, both levosimendan and cilostazol revealed 
      effectiveness in attenuating the severity of HFD/isoproterenol-induced myocardial 
      injury as revealed by electrocardiogram signs, apoptotic markers, and 
      histopathological score via counteracting the oxidative stress burden, increments 
      in the expression of inflammatory mediators, and modulating nuclear factor 
      kappa-B (NF-kappaB) and phosphatidylinositide 3-kinases (PI3K)/protein kinase B 
      (Akt)/ mechanistic target of rapamycin (mTOR) pathway. It was obvious that 
      levosimendan offered more cardioprotective properties than cilostazol. The study 
      showed the relations between hyperlipedemia, hyperaggregability state, and 
      myocardial injury with the modulation of NF-kappaB and PI3K/Akt/mTOR pathway.
FAU - Tawfik, Mona K
AU  - Tawfik MK
AD  - 1 Department of Pharmacology, Faculty of Medicine, Suez Canal University, 
      Ismailia, Egypt.
FAU - El-Kherbetawy, Mohamed K
AU  - El-Kherbetawy MK
AD  - 2 Department of pathology, Faculty of Medicine, Suez Canal University, Ismailia, 
      Egypt.
FAU - Makary, Samy
AU  - Makary S
AD  - 3 Department of Physiology, Faculty of Medicine, Suez Canal University, Ismailia, 
      Egypt.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20180423
PL  - United States
TA  - J Cardiovasc Pharmacol Ther
JT  - Journal of cardiovascular pharmacology and therapeutics
JID - 9602617
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipids)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 349552KRHK (Simendan)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - L628TT009W (Isoproterenol)
RN  - N7Z035406B (Cilostazol)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Cilostazol/*pharmacology
MH  - *Diet, High-Fat
MH  - Disease Models, Animal
MH  - Heart Rate/drug effects
MH  - Inflammation Mediators/metabolism
MH  - *Isoproterenol
MH  - Lipids/blood
MH  - Myocardial Infarction/chemically induced/enzymology/pathology/*prevention & 
      control
MH  - Myocytes, Cardiac/*drug effects/enzymology/pathology
MH  - Phosphatidylinositol 3-Kinase/*metabolism
MH  - Platelet Aggregation/*drug effects
MH  - Platelet Aggregation Inhibitors/*pharmacology
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Signal Transduction/drug effects
MH  - Simendan/*pharmacology
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - acute myocardial infarction
OT  - cilostazol
OT  - high-fat diet
OT  - levosimendan
OT  - platelet aggregation
OT  - rats
EDAT- 2018/04/25 06:00
MHDA- 2019/06/25 06:00
CRDT- 2018/04/25 06:00
PHST- 2018/04/25 06:00 [pubmed]
PHST- 2019/06/25 06:00 [medline]
PHST- 2018/04/25 06:00 [entrez]
AID - 10.1177/1074248418763957 [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol Ther. 2018 Sep;23(5):456-471. doi: 
      10.1177/1074248418763957. Epub 2018 Apr 23.