PMID- 15078585
OWN - NLM
STAT- MEDLINE
DCOM- 20040729
LR  - 20191108
IS  - 1061-5377 (Print)
IS  - 1061-5377 (Linking)
VI  - 12
IP  - 3
DP  - 2004 May-Jun
TI  - Peroxisome proliferator activator receptors (PPAR), insulin resistance, and 
      cardiomyopathy: friends or foes for the diabetic patient with heart failure?
PG  - 158-70
AB  - Diabetes is a risk factor for coronary atherosclerosis, myocardial infarction, 
      and ischemic cardiomyopathy. Insulin resistance is associated with left 
      ventricular (LV) hypertrophy and hypertensive cardiomyopathy. Even in the absence 
      of coronary artery disease or hypertension, "diabetic cardiomyopathy" can develop 
      because of myocardial autonomic dysfunction or impaired coronary flow reserve. 
      The relationship between insulin resistance and cardiomyopathy is bidirectional. 
      Systemic and myocardial glucose uptake is compromised in heart failure 
      independent of etiology. These abnormalities are associated with cellular 
      deficits of insulin signaling. Insulin resistance in heart failure can be 
      detrimental, because transcriptional shifts in metabolic gene expression favor 
      glucose over fat as a substrate for high-energy phosphate production. Although 
      preexisting diabetes accelerates this process of "metabolic death," insulin 
      resistance can also develop secondary to cardiomyopathy-associated overabundance 
      of neurohormones and cytokines. Insulin resistance and fatty acid excess are 
      potential therapeutic targets in heart failure, striving for efficient myocardial 
      substrate utilization. Peroxisome proliferator activator receptor gamma 
      (PPARgamma) agonists are antidiabetic agents with antilipemic and 
      insulin-sensitizing activity. Experimental studies suggest salutary effects in 
      limiting infarct size, attenuating myocardial reperfusion injury, inhibiting 
      hypertrophic signaling and vascular antiinflammatory actions through cytokine 
      inhibition. However, clinical applicability in diabetic patients experiencing 
      heart failure has been hampered because of increased edema and even fewer reports 
      of exacerbation associated with these compounds. Evidence to date argues for 
      peripheral mechanisms of edema unrelated to central hemodynamics. Nevertheless, 
      they are currently contraindicated in New York Heart Association (NYHA) III-IV 
      patients, particularly in combination with insulin. Investigations are underway 
      to decipher mechanisms, risks, and benefits of PPARgamma agonists, as well as the 
      role of the structurally related PPARalpha receptor on cardiovascular metabolism 
      and function.
FAU - Nikolaidis, Lazaros A
AU  - Nikolaidis LA
AD  - Division of Cardiology, Department of Medicine, Drexel University College of 
      Medicine, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212, USA.
FAU - Levine, T Barry
AU  - Levine TB
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Cardiol Rev
JT  - Cardiology in review
JID - 9304686
RN  - 0 (Cytokines)
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Cardiomyopathies/*drug therapy/etiology/physiopathology
MH  - Cytokines/metabolism
MH  - Diabetes Complications
MH  - Diabetes Mellitus/*drug therapy/physiopathology
MH  - Fatty Acids, Nonesterified/metabolism
MH  - Heart Failure/drug therapy/etiology/physiopathology
MH  - Humans
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Insulin Resistance/physiology
MH  - Neurotransmitter Agents/metabolism
MH  - Receptors, Cytoplasmic and Nuclear/*agonists
MH  - Thiazolidinediones/*therapeutic use
MH  - Transcription Factors/*agonists
RF  - 146
EDAT- 2004/04/14 05:00
MHDA- 2004/07/30 05:00
CRDT- 2004/04/14 05:00
PHST- 2004/04/14 05:00 [pubmed]
PHST- 2004/07/30 05:00 [medline]
PHST- 2004/04/14 05:00 [entrez]
AID - 00045415-200405000-00008 [pii]
AID - 10.1097/01.crd.0000102419.52594.90 [doi]
PST - ppublish
SO  - Cardiol Rev. 2004 May-Jun;12(3):158-70. doi: 10.1097/01.crd.0000102419.52594.90.