Impact of lysophosphatidylcholine on survival and function of UEA-1(+)acLDL (+) endothelial progenitor cells in patients with coronary artery disease.

Lysophosphatidylcholine (LPC) generated from oxidized low-density lipoprotein by lipoprotein-associated phospholipase A2 plays a key role in plaque inflammation and vulnerability. Endothelial progenitor cells (EPCs) can repair injured endothelium and exert anti-inflammatory effects of vulnerable plaque. We study the impact and mechanisms of LPC on UEA-1 and acLDL binding EPCs (UEA-1(+)acLDL(+) EPCs). UEA-1(+)acLDL(+) EPCs from coronary artery disease (CAD) patients were cultured and exposed to LPC at different concentrations and different timepoints. We determined the significant concentration (40 µM). UEA-1(+)acLDL(+) EPCs were preincubated for 30 min with pravastatin (20 µM) with LY249002, a specific inhibitor of the Akt signaling pathway, and exposed for 24 h to LPC 40 µM. The survival, migration, adhesion, and proliferation of UEA-1(+)acLDL(+) EPCs were assessed. To examine the mechanisms of LPC toxicity and pravastatin effects, phosphorylated Akt and endothelial nitric oxide synthase (eNOS) levels and the ratio of Bcl-2/Bax protein expression were assessed. LPC induced apoptosis and impaired migration and adhesion of UEA-1(+)acLDL(+) EPCs significantly. The detrimental effects of LPC were attenuated by pravastatin. However, when UEA-1(+)acLDL(+) EPCs were pretreated with pravastatin and LY249002, a specific inhibitor of the Akt signaling pathway, simultaneously, the beneficial effects of pravastatin were abolished. Furthermore, LPC suppressed Akt and eNOS phosphorylation and increased Bcl-2/Bax expression. The effects of LPC on Akt/eNOS and Bcl-2/Bax activity were reversed by pravastatin. In conclusion, LPC inhibited UEA-1(+)acLDL(+) EPCs survival and impaired its functions, and these were attributable to inhibition of the Akt/eNOS and Bcl-2/Bax pathway. Pravastatin reversed the detrimental action of LPC. These findings suggest that LPC inhibition can be a possible strategy for CAD through EPC revitalization.

Association of hyper-LDL cholesterolemia with increased risk of colorectal adenoma.

BACKGROUND/AIMS: Previous studies on the association between dyslipidemia and the presence of colorectal adenoma showed conflicting results, and were limited due to small sample sizes, inconsistent definitions of dyslipidemia, or a lack of data on full lipid profiles. The aim of this study was to determine the association between colorectal adenomas and dyslipidemia according to the definition by the National Cholesterol Education Program- Adult Treatment Panel III. METHODOLOGY: We conducted a retrospective, cross-sectional study in subjects who underwent screening colonoscopy and blood tests for full lipid profiles. Serum dyslipidemia profiles were compared between the adenoma group and the control group, and multivariate analysis was performed to identify independent predictors of the presence of colorectal adenomas. RESULTS: Patients with hyper-LDL cholesterolemia were more frequently included in the adenoma group than the control group (46.7% vs. 32.1%, respectively, p=0.023), and hyper-LDL cholesterolemia (OR = 1.954, 95% CI=0.981-3.893, p=0.057) showed a statistical trend for the positive association with the presence of colorectal adenomas by multivariate analysis. Furthermore, proximal colorectal adenomas were more prevalent in the hyper-LDL cholesterolemia group than in the normal LDL cholesterolemia group (p=0.026). CONCLUSIONS: Hyper-LDL cholesterolemia was associated with the presence of colorectal adenomas, especially in the proximal colon.

Changes in Serum Osteocalcin are Not Associated with Changes in Glucose or Insulin for Osteoporotic Patients Treated with Bisphosphonate.

BACKGROUND: Bisphosphonate is used in osteoporosis treatment to repress osteoclast activity, which then decreases levels of osteocalcin (OC). OC, a protein secreted by osteoblasts and released from the bone matrix during osteoclastic bone resorption, has been found to control blood glucose levels by increasing insulin production and sensitivity. The question addressed in this study is whether decreasing OC through bisphosphonate treatment will provoke a change in glucose homeostasis. METHODS: Eighty-four patients with osteoporosis were treated with once-weekly risedronate 35 mg and cholecalciferol 5,600 IU. We measured fasting plasma glucose (FPG), insulin, and undercarboxylated (Glu) and carboxylated (Gla) OC levels at baseline and after 16 weeks. To estimate insulin resistance (IR) and ß-cell function (B)%, homeostasis model assessment (HOMA)-IR and HOMA-B% were also calculated, respectively. RESULTS: The mean FPG level in total subjects increased significantly from 5.3 to 5.5 mmol/L, but no changes in blood glucose were noted in the 24 subjects with impaired fasting glucose. Glu and Gla OC levels declined significantly after treatment. No correlations were observed between changes in OC and changes in glucose, however. CONCLUSIONS: Bisphosphonate treatment for osteoporosis reduced OC, but this change was not associated with changes in glucose metabolism.