Microvesicles from the plasma of elderly subjects and from senescent endothelial cells promote vascular calcification.

Vascular calcification is commonly seen in elderly people, though it can also appear in middle-aged subjects affected by premature vascular aging. The aim of this work is to test the involvement of microvesicles (MVs) produced by senescent endothelial cells (EC) and from plasma of elderly people in vascular calcification. The present work shows that MVs produced by senescent cultured ECs, plus those found in the plasma of elderly subjects, promote calcification in vascular smooth muscle cells. Only MVs from senescent ECs, and from elderly subjects' plasma, induced calcification. This ability correlated with these types of MVs' carriage of: a) increased quantities of annexins (which might act as nucleation sites for calcification), b) increased quantities of bone-morphogenic protein, and c) larger Ca contents. The MVs of senescent, cultured ECs, and those present in the plasma of elderly subjects, promote vascular calcification. The present results provide mechanistic insights into the observed increase in vascular calcification-related diseases in the elderly, and in younger patients with premature vascular aging, paving the way towards novel therapeutic strategies.

Aging-associated oxidized albumin promotes cellular senescence and endothelial damage.

Increased levels of oxidized proteins with aging have been considered a cardiovascular risk factor. However, it is unclear whether oxidized albumin, which is the most abundant serum protein, induces endothelial damage. The results of this study indicated that with aging processes, the levels of oxidized proteins as well as endothelial microparticles release increased, a novel marker of endothelial damage. Among these, oxidized albumin seems to play a principal role. Through in vitro studies, endothelial cells cultured with oxidized albumin exhibited an increment of endothelial damage markers such as adhesion molecules and apoptosis levels. In addition, albumin oxidation increased the amount of endothelial microparticles that were released. Moreover, endothelial cells with increased oxidative stress undergo senescence. In addition, endothelial cells cultured with oxidized albumin shown a reduction in endothelial cell migration measured by wound healing. As a result, we provide the first evidence that oxidized albumin induces endothelial injury which then contributes to the increase of cardiovascular disease in the elderly subjects.

Changes in endothelial microparticles and endothelial progenitor cells in obese patients in response to surgical stress.

BACKGROUND: Obese patients undergoing surgery are at increased risk of intraoperative and postoperative cardiovascular complications. The present study was designed to study the changes in endothelial microparticles, endothelial progenitor cells, and adipokines in obese patients in response to limb ischemia during knee surgery. METHODS: This prospective study included seventy-four patients who underwent total knee arthroplasty. Patients were stratified in tertiles according to their body mass index. Flow cytometry was used for quantification and characterization of endothelial microparticles, endothelial progenitor cells, and adipokines. ELISA (enzyme-linked immunosorbent assay) was used to measure the adiponectin level. RESULTS: The number of endothelial microparticles was greater in obese compared with nonobese patients. The number of endothelial microparticles increased further immediately after surgery in all tertiles. Three days after surgery, endothelial microparticles returned to the basal preoperative level except in the most obese patients. The percentage of endothelial progenitor cells was lower in obese patients. Concentrations of adipokines increased after surgery, but the increase was more accentuated in obese patients. CONCLUSIONS: Obese patients present with a high number of endothelial microparticles, a low number of endothelial progenitor cells, and high levels of adipokines, with further increases in adipokines after surgery, suggesting an inflammatory condition that worsens after surgery and may affect endothelial repair.