Endothelial inflammation in insulin resistance.
BACKGROUND
Type 2 diabetes and attendant cardiovascular morbidity are becoming major health concerns globally. Obesity-related type 2 diabetes is rapidly rising in prevalence, probably largely because of increased longevity and sedentary lifestyles. Insulin resistance and type 2 diabetes are associated with increased coronary heart disease, but the severity of glycaemia during the diabetic phase can only to a minor extent explain the increased risk. Increased levels of the acute-phase inflammatory marker, C-reactive protein (CRP), are related to insulin resistance and the metabolic syndrome, suggesting a role for chronic low-grade inflammation. CRP levels might predict the development of type 2 diabetes.


BACKGROUND
Subodh Verma and associates (Circulation 2004; 109: 2058-67) recently showed that CRP attenuates the survival, differentiation, and function of endothelial progenitor cells, partly by CRP reducing expression of endothelial nitric-oxide synthase. Rosiglitazone, a peroxisome-proliferator-activator receptor gamma agonist, inhibits the negative effects of CRP on endothelial progenitor cells. The results are consistent with the suggestion that CRP directly promotes atherosclerotic processes and endothelial cell inflammation. CRP might thus directly trigger the development of a proinflammatory and proatherosclerotic state, leading to atherothrombosis.


CONCLUSIONS
Cell-surface CRP receptors and signalling pathways need to be characterised. From such study might come novel drugs that will defer proinflammatory reactions leading to insulin resistance and atherothrombosis.
Sjöholm
Ake
A
Department of Internal Medicine, Karolinska Institutet, Stockholm South Hospital, SE-118 83 Stockholm, Sweden. ake.sjoholm@sodersjukhuset.se
Nyström
Thomas
T
D001161:Arteriosclerosis / Q000503:physiopathology; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D018836:Inflammation Mediators / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D024821:Metabolic Syndrome / Q000503:physiopathology
D015415:Biomarkers; D018836:Inflammation Mediators; D002097:C-Reactive Protein