Adiponectin and Cardiovascular Disease
Response to Therapeutic Interventions
Seung Hwan Han, MD, PhD*,
Michael J. Quon, MD, PhD ,
Jeong-a Kim, PhD and
Kwang Kon Koh, MD, PhD, FACC*,*
* Division of Cardiology, Gil Heart Center, Gachon Medical School, Incheon, Korea
Diabetes Unit, Laboratory of Clinical Investigation, NCCAM, NIH, Bethesda, Maryland
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Figure 1 Antiatherogenic Effects of Adiponectin
Adiponectin has novel vascular actions to directly stimulate production of nitric oxide (NO) in endothelial cells using phosphatidylinositol (PI) 3-kinase-dependent pathways involving phosphorylation of endothelial nitric oxide synthase (eNOS) by adenosine-monophosphate-activated protein kinase (AMPK) (7) and reduces expression of adhesion molecules and decreases cytokine production from macrophage by inhibiting nuclear transcription factor kappa B (NF- B) signaling through cyclic adenosine-monophosphate-dependent pathways (23,24). Modified from Koh KK, Han SH, Quon MJ. Inflammatory markers and the metabolic syndrome: insights from therapeutic interventions. J Am Coll Cardiol 2005;46:1978–85. IB = inhibitory kappa B.
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Figure 2 Mechanisms of Therapeutic Interventions on Adiponectin, Insulin Resistance, and Endothelial Function
Lifestyle modifications and cardiovascular drugs such as fenofibrate, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II type I receptor blockers (ARBs), and thiazolidinediones (TZDs) increase plasma levels of adiponectin, reduce insulin resistance, and improve endothelial function. These may be one mechanism to reduce cardiovascular diseases by these therapeutic interventions used in recent clinical trials.
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Figure 3 Reciprocal Relationships Between Vascular and Metabolic Actions of Insulin in Health and Disease
(A) Parallel phosphatidylinositol (PI) 3-kinase-dependent insulin signaling pathways in metabolic and vascular tissues synergistically couples metabolic and vascular physiology under healthy conditions. (B) Parallel impairment in insulin signaling pathways under pathological conditions contributes to synergistic coupling of insulin resistance (IR) and endothelial dysfunction (80). eNOS = endothelial nitric oxide synthase; FFA = free fatty acid; IKKß = inhibitor of nuclear factor kappa B kinase beta; IRS = insulin receptor substrate; NO = nitric oxide; PDK = phosphoinositide-dependent kinase; PKC = protein kinase C zeta.
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