Objective: We investigated whether hyperglycemia and/or free fatty acids (palmitate, PAL) affect the expression level of bone morphogenic protein 4 (BMP4), a proatherogenic marker, in endothelial cells and the potential role of BMP4 in diabetic vascular complications. Design and Method: To measure BMP4 expression, human umbilical vein endothelial cells (HUVECs) were exposed to high glucose concentrations and/or PAL for 24 or 72 h, and the effects of these treatments on the expression levels of adhesion molecules and reactive oxygen species (ROS) were examined. BMP4 loss-of-function status was achieved via transfection of a BMP4-specific siRNA. Results: High glucose levels increased BMP4 expression in HUVECs in a dose-dependent manner. PAL potentiated such expression. The levels of adhesion molecules and ROS production increased upon treatment with high glucose and/or PAL, but this effect was negated when BMP4 was knocked down via siRNA. Signaling of BMP4, a proinflammatory and pro-atherogenic cytokine marker, was increased by hyperglycemia and PAL. BMP4 induced the expression of inflammatory adhesion molecules and ROS production. Conclusions: Our work suggests that BMP4 plays a role in atherogenesis induced by high glucose levels and/or PAL.
Abstract Lifestyle changes after a diagnosis of type 2 diabetes mellitus (T2DM) can affect vascular health outcomes. The objective of this study was to investigate the effects of changes in smoking and exercise on the risk of cardiovascular disease (CVD) and mortality in patients with newly diagnosed T2DM. Data were analyzed for 181,591 people with newly diagnosed T2DM who underwent 2 serial health examinations within 2 years before and after diagnosis of diabetes. The study population was followed from the baseline to the date of death or cardiovascular events, or until December 31, 2018 and median follow-up was 6. 07 years. Based on the change in status from before to after the diagnosis of T2DM, participants were grouped into smoking groups (continuous smokers, quitters, new smokers, and nonsmokers) and exercise groups (constant exercisers, new exercisers, exercise dropouts, and non-exercisers). Compared with the non-exercisers, those who initiated exercise after their diagnosis had a lower risk of myocardial infarction (MI), stroke, and all-cause mortality: the hazard ratio (HR; 95% confidence interval [CI]) was 0.85 (0.76–0.94) for MI, 0.86 (0.78–0.94) for stroke, and 0.84 (0.89–0.90) for all-cause mortality. Quitters had a higher risk of MI, stroke, and all-cause mortality than nonsmokers, but their risk level was much lower than that in continuous smokers. Whenthe group ofcontinuous smokers and non-exercisers was considered as the reference group,participants who quit smoking and remained non-exercisers had a 21% lower risk of CVD (HR 0.79; 95% CI 0.70–0.90). Those who quit smoking and started exercising had a 46% reduced risk of CVD (HR 0.54; 95% CI 0.41–0.71) and a 22% reduced risk in all-cause mortality (HR 0.78; 95% CI 0.63–0.96). Smoking cessation and exercise initiation after a diagnosis of new-onset T2DM was associated with a reduced risk of CVD and all-cause mortality. Presentation: No date and time listed
Here, we investigated whether hyperglycemia and/or free fatty acids (palmitate, PAL) aff ect the expression level of bone morphogenic protein 4 (BMP4), a proatherogenic marker, in endothelial cells and the potential role of BMP4 in diabetic vascular complications. To measure BMP4 expression, human umbilical vein endothelial cells (HUVECs) were exposed to high glucose concentrations and/or PAL for 24 or 72 h, and the effects of these treatments on the expression levels of adhesion molecules and reactive oxygen species (ROS) were examined. BMP4 loss-of-function status was achieved via transfection of a BMP4-specific siRNA. High glucose levels increased BMP4 expression in HUVECs in a dose-dependent manner. PAL potentiated such expression. The levels of adhesion molecules and ROS production increased upon treatment with high glucose and/or PAL, but this eff ect was negated when BMP4 was knocked down via siRNA. Signaling of BMP4, a proinflammatory and pro-atherogenic cytokine marker, was increased by hyperglycemia and PAL. BMP4 induced the expression of infl ammatory adhesion molecules and ROS production. Our work suggests that BMP4 plays a role in atherogenesis induced by high glucose levels and/or PAL.
Idiopathic hypoparathyroidism is a relatively rare disease characterized by hypocalcemia and hyperphosphatemia: this is due to a deficiency or a sereretory disorder of the parathyroid hormone without any prior operation nor underlying medical disoder. Calcium carbonate and vitamin D substitution are generally considered as the mainstay of therapy, but these treatments can cause hypercalcemia and hypercalciuria. Persistent ingestion of large amount of calcium carbonate can cause milk-alkali syndrome that is characterized by hypercalcemia, metabolic alkalosis and renal failure. Once a patient is diagnosed with milk-alkali syndrome, withdrawal of calcium carbonate and vitamin D is essential and treatment with saline diuresis and furosemide is the usually effective. In treatmenf of hypoparathyroidism with calcium carbonate and vitamin D substitution, evaluation of serum calcium and urinary calcium excretion is essential to avoid hypercalcemia and hypercalciuria. We concluded that during treatment with calcium carbonate and vitamin D substitution for patients with idiopathic hypoparathyroidism, they should have carefully laboratory monitoring, and they should be made aware of the circumstances influencing calcium metabolism.
Background Endothelial-to-mesenchymal transition (EndMT) contributes to inflammatory conditions inducing conversion of endothelial cells (ECs) into activated fibroblasts, promoting fibrotic diseases. Pro-inflammatory cytokine is the most potent inducer of EndMT. We investigated inhibition of interleukin-1β (IL-1β)-induced EndMT by gemigliptin, a dipeptidyl peptidase-IV inhibitor. Methods We exposed human umbilical vein endothelial cells (HUVECs) to 10 ng/mL IL-1β/20 μM gemigliptin and analyzed the expression of endothelial, smooth muscle, mesenchymal, and osteoblastic markers, bone morphogenetic protein (BMP), Smad, and non-Smad signaling pathway proteins. Results Morphological changes showed gemigliptin blocked IL-1β-induced EndMT, upregulated EC markers, and downregulated smooth muscle and mesenchymal markers. IL-1β activation of HUVECs is initiated by the BMP/Smad and non-smad BMP signaling pathways. Gemigliptin inhibited IL-1β induction of BMP2 and 7, activin receptor type IA, BMP receptor type IA, and BMP receptor type II. Reversal of IL-1β-mediated inhibition of BMP-induced Smad1/5/8, Smad2, and Smad3 phosphorylation by gemigliptin suggests involvement of the Smad pathway in gemigliptin action. In the non-Smad BMP pathway, gemigliptin treatment significantly increased the deactivation of extracellular regulated protein kinase (ERK), p38, and JNK by IL-1β. Gemigliptin treatment suppressed BMP-2-induced expression of key osteoblastic markers including osterix, runt-related transcription factor 2, and hepcidin during IL-1β-induced EndMT. Conclusion We demonstrated a novel protective mechanism of gemigliptin against fibrosis by suppressing IL-1β-induced EndMT. Keywords: LC15-0444; Dipeptidyl-peptidase IV inhibitors; Interleukin-1beta; Bone morphogenetic proteins; Endothelial-to-mesenchymal transition
Cushing's disease is a disorder of hypercortisolism caused by a pituitary micro- or macro-adenoma. Most patients with Cushing's disease have a bilateral adrenal enlargement, which depends on the duration of the disease, as a result of the long standing ACTH stimulation of both adrenal glands. However, in macronodular adrenocortical hyperplasia (MNH) that is caused by Cushing's disease, if the MNH gains autonomy, a bilateral adrenalectomy, as well as the removal of pituitary adenoma, is often essential. We encountered a patient diagnosed with Cushing's disease with bilateral adrenal tuberculosis simulating MNH. She had taken anti-tuberculosis medications one year prior to admission due to spinal tuberculosis. Sellar MRI revealed a pituitary macroadenoma, but adrenal CT showed enlargement in both adrenal glands that appeared to be MNH. A hormonal study and bilateral inferior petrosal sinus sampling revealed Cushing's disease. Therefore, she underwent trans-sphenoidal surgery of the pituitary mass. The pituitary surgery was successful and the serum cortisol returned to normal range. However, the adrenal mass rapidly enlarged after removing the pituitary tumor without showing evidence of a recurrence or adrenal autonomy of hypercortisolism. Accordingly, a laparoscopic left adrenalectomy was performed to examine the nature of the mass. The resected left adrenal gland was pathologically determined to have a lesion of tuberculosis with some part of the intact cortex. So we assumed that the cause of rapid adrenal enlargement might be due to adrenal tuberculosis. In summary, to the best of our knowledge, this is the first case of Cushing's disease coexisting with both adrenal tuberculosis simulating a bilateral MNH.
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