Metabolic syndrome and diabetic atherothrombosis: Implications in vascular complications

P. Meerarani, Juan J. Badimon, E. Zias, Valentin Fuster, Pedro R. Moreno

Research output: Contribution to journalReview articlepeer-review

52 Scopus citations

Abstract

Metabolic syndrome is characterized by the clustering of a number of metabolic abnormalities in the presence of underlying insulin resistance with a strong association with diabetes and cardiovascular disease morbidity and mortality. The disorder is defined in different ways, but the pathophysiology is attributable to insulin resistance. An increased release of free fatty acids (FFAs) from adipocytes block insulin signal transduction pathway, induce endothelial dysfunction due to increased reactive oxygen species (ROS) generation and oxidative stress. Dyslipidemia, associated with high levels of triglycerides and low concentrations of high density lipoproteins (HDLs), contributes to a proinflammatory state. Inflammation, the key pathogenic component of atherosclerosis, promotes thrombosis, a process that underlies acute coronary event and stroke. Tissue factor, a potent trigger of the coagulation cascade, is increased in diabetes with poor glycemic control. Therapeutic lifestyle changes (weight loss and physical activity) along with pharmacological interventions are recommended to prevent the complications of metabolic syndrome. In addition to statins, metformin, blood pressure lowering medications, interventions to increase HDLs are other important approaches to decrease the risk of cardiovascular disease. Furthermore, the peroxisome proliferator activated receptor (PPAR) - alpha and gamma agonists are potent anti-inflammatory and anti-atherogenic agents that could both improve insulin sensitivity and the long-term cardiovascular risk. In this review we focus on the molecular and pathophysiological basis of metabolic syndrome, which augments diabetes (insulin resistance) and the contribution of neovascularization in the plaque progression in diabetes, leading to rupture and coronary thrombosis.

Original languageEnglish
Pages (from-to)501-514
Number of pages14
JournalCurrent Molecular Medicine
Volume6
Issue number5
DOIs
StatePublished - Aug 2006

Keywords

  • Atherosclerosis
  • Endothelial dysfunction
  • Metabolic syndrome
  • Obesity
  • Peroxisome proliferator activator receptor
  • Reactive oxygen species
  • Type 2 diabetes mellitus

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