Role of Lipotoxicity in Endothelial Dysfunction

Abstract

SUMMARY Lipotoxicity, caused in large part by overnutrition, directly leads to endothelial dysfunction. Excess lipids in both the circulation and at the tissue level contribute to endothelial dysfunction that underlies much of the pathophysiology of both metabolic disease, including obesity and diabetes and their CV complications. Direct lipotoxic effects on other organs as well as secondary insults from endothelial dysfunction synergize to cause substantial morbidity and mortality. Lifestyle interventions, including reduced calorie intake, diet, and exercise as well as a variety of pharmacologic interventions targeting various mechanisms underlying lipotoxicity in vascular endothelium significantly modify metabolic and CV risk.

Adverse effects of glucocorticoids: coagulopathy

“…Previous studies have observed decreased availability of nitric acid in patients with obesity (22), DM (23), hypertension (24), dyslipidemia (25), and insulin resistance (26), all of which are complications that are frequently associated with CS. Insulin regulates the balance between the levels of nitric acid and endothelin 1 by phosphatidylinositol 3-kinase (PI3K) and MAPK respectively.…”

Palmitate-induced inflammatory pathways in human adipose microvascular endothelial cells promote monocyte adhesion and impair insulin transcytosis

“…Our findings open new perspectives to decipher the mechanisms involved and identify targets to restore insulin transit. The PAinduced reduction in insulin transcytosis across HAMEC suggests the possibility that functional alterations may occur at the level of the microvasculature during the metabolic syndrome, in addition to the well-documented defects in large vessel vasodilation (25).…”

“…Deleterious effects of saturated fatty acids have been described in many different cell types (25). Long-term exposure to high concentrations of saturated fatty acids have previously been found to trigger apoptosis in cells in culture.…”

Effect of Simvastatin on the Prognosis and the Changes of the Clinical Status in Patients With Acute Ischemic Stroke. The Results of the 12 Month Randomized, Open Comparative Study

“…Доказано, что статины обладают способностью восстанавливать функцию эндотелия и тем самым способствовать нормальному вазомоторному ответу коронарных и периферических артерий. Стати-ны улучшают функцию эндотелия при сахарном диабете [31,32] за счет снижения липотоксичности [33]. Следует подчеркнуть, что это свойство статинов проявляется уже при малых дозах и для этого не требуется продолжи- Группа II тельных сроков лечения [34].…”