Reciprocal relationships between abnormal metabolic parameters and endothelial dysfunction.
OBJECTIVE
Endothelial dysfunction plays a crucial role in the pathogenesis of atherosclerosis and related cardiovascular diseases. Glucotoxicity, lipotoxicity, and inflammation all independently contribute to development of both endothelial dysfunction and insulin resistance. We review pathophysiological mechanisms underlying reciprocal relationships between endothelial dysfunction and insulin resistance and recent insights from therapeutic interventions to improve both metabolic and vascular function.


RESULTS
Shared causal factors such as glucotoxicity, lipotoxicity, and inflammation interact at multiple levels creating reciprocal relationships between insulin resistance and endothelial dysfunction that help to explain frequent clustering of metabolic and cardiovascular disorders. Metabolic abnormalities implicated in the development of insulin resistance, including hyperglycemia, elevated levels of free fatty acids, accumulation of advanced glycation end products, dyslipidemias, and decreased levels of adiponectin, also contribute importantly to endothelial dysfunction. Diet, exercise, cardiovascular drugs, and insulin sensitizers simultaneously improve endothelium-dependent vascular function, reduce inflammation, and improve insulin sensitivity by both distinct and interrelated mechanisms.


CONCLUSIONS
Pathophysiological mechanisms underlying reciprocal relationships between endothelial dysfunction and insulin resistance contribute to clustering of metabolic and cardiovascular diseases represented by the metabolic syndrome. Therapeutic interventions that target endothelial dysfunction or insulin resistance often simultaneously improve both metabolic and vascular function.
Han
Seung Hwan
SH
Division of Cardiology, Gachon Medical School, Incheon, South Korea.
Quon
Michael J
MJ
Koh
Kwang Kon
KK
D004032:Diet; D004041:Dietary Fats; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified; D006801:Humans; D007333:Insulin Resistance; D008659:Metabolic Diseases / Q000503:physiopathology*
D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified