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EXPRESS: Plasma from Type 1 Diabetes Patients Promotes Pro-atherogenic Cholesterol Transport in Human Macrophages

Accacha, Siham Acacha; Kasselman, Lora J; Mejia-Corletto, Jorge; Srivastava, Ankita; Voloshyna, Iryna; Renna, Heather A; De Leon, Joshua; Levine, Robert L; Reiss, Allison Bethanne
Hyperglycemia, one of the major risk factors for atherosclerosis, leads to the accumulation of Advanced glycation end products (AGEs), contributing to cardiovascular complications. Such accumulation may accelerate the progression of vascular disease in patients with diabetes. Reverse cholesterol transport (RCT) protein, ATP-binding membrane cassette transporters A1 and G1 (ABCA1 and ABCG1) and cholesterol 27-hydroxylase facilitate cholesterol removal from macrophages. AGE inhibits reverse cholesterol transport by reducing the expression of ABCA1 and ABCG1. This study aimed to evaluate whether plasma from poorly controlled adolescents with type 1 diabetes (T1D) disrupts cholesterol homeostasis in human monocytes/macrophages. Twenty healthy controls (HC) and 20 patients with T1DM, 10 to 19 years old, were enrolled. Naïve THP-1 macrophages were exposed to plasma from each HC and patient with T1D. Following incubation, mRNA for cholesterol efflux (ABCA1, ABCG1, 27-hydroxylase) and cholesterol uptake (CD36, ScR-A1, lectin oxidized low-density lipoprotein (LOX)-1, CXCL16) were isolated. Foam cell formation was quantified to confirm the pro-atherogenic effects of T1D plasma on macrophages. Results showed that T1D plasma had an elevated level of CML-modified proteins and upregulated CXCL16 and, to a lesser degree, ScR-A1. This change in gene expression in the presence of T1D plasma is associated with increased lipid accumulation and foam cell formation by THP-1 macrophages. In our study, these cells' uptake of an AGE product occurred mainly through the SR-A1 and CXCL16 receptors, leading to increased intracellular oxidized LDL. We conclude that AGEs may contribute to accelerated atherosclerosis in diabetes through effects on both forward and reverse cholesterol movement.
PMID: 39417428
ISSN: 1708-8267
CID: 5718702

Central adrenal insufficiency screening with morning plasma cortisol and ACTH levels in Prader-Willi syndrome

Angulo, Moris A; Butler, Merlin G; Hossain, Waheeda A; Castro-Magana, Mariano; Corletto, Jorge
BACKGROUND:Prader-Willi syndrome (PWS) is a complex genetic disorder with severe hypotonia, failure to thrive, childhood obesity, hypogonadism/hypogenitalism and learning/behavioral problems with endocrine-related growth and other hormone deficiencies. The prevalence of central adrenal insufficiency (CAI) using dynamic testing ranges from rare to 60%. We compared routine morning plasma cortisol (MPC) and ACTH levels in large cohorts of PWS and control children to address CAI. METHODS:Retrospective analysis of MPC and ACTH levels was undertaken in 128 PWS growth hormone (GH)-treated children under medical care before considering dynamic testing for CAI and 128 non-syndromic control children with short stature evaluated for GH deficiency. RESULTS: 8.0 pg/mL with one individual having an initial low plasma ACTH level (8 pg/mL), but normal upon repeat. CONCLUSIONS:
PMID: 35437976
ISSN: 2191-0251
CID: 5218222

PRO-ATHEROGENIC PROPERTIES OF PLASMA FROM PATIENTS WITH TYPE 1 DIABETES MELLITUS: EFFECTS ON MACROPHAGE LIPID HANDLING [Meeting Abstract]

DeLeon, Joshua R; Corletto, Jorge Mejia; Accacha, Siham; Voloshyna, Iryna; Siegart, Nicolle; Kasselman, Lora; Magana, Mariano Castro; Reiss, Allison
ISI:000397342302789
ISSN: 1558-3597
CID: 2677992

BLOCKADE OF THE RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS IS NOT SUFFICIENT TO PREVENT ATHEROGENIC DISRUPTION OF LIPID METABOLISM BY PLASMA FROM TYPE 1 DIABETES PATIENTS: A CLUE IN THE SEARCH FOR IMPROVED CARDIOVASCULAR HEALTH IN DIABETES [Meeting Abstract]

Accacha, Siham; Reiss, Allison B; Mejia-Corletto, Jorge; Siegart, Nicolle M; Renna, Heather A; Castro-Magana, Mariano; De Leon, Joshua; Kasselman, Lora J
ISI:000399374600045
ISSN: 1708-8267
CID: 2678062

Long-Acting Growth Hormone: An Update

Saenger, Paul H; Mejia-Corletto, Jorge
After the introduction of recombinant human growth hormone (rhGH) in 1985, a myriad of children and adults have benefited from its growth-promoting and metabolic effects. Nowadays, current therapeutic regimens rely on daily subcutaneous GH injections that could be burdensome and inconvenient to pediatric patients. As expected with any long-term parenteral pharmacological treatment, these daily regimens may promote nonadherence, poor compliance, treatment abandonment and/or suboptimal clinical outcomes. In order to improve patient and caregiver acceptance of proposed regimens, simplified dosing schedules could potentially aid in reducing poor compliance and maximize the therapeutic end results. Long-acting GH formulations have been designed and perfected over the last two decades, and currently there are several formulations in advanced stages of research as a reasonable attempt to improve patient's adherence to GH treatment. A long-acting GH preparation allowing for reduced injection frequency is likely to improve treatment adherence and to decrease the distress and inconvenience associated with daily injections. This review presents an update about the status of current and recent efforts that have enabled the formulation of sustained-release, long-acting rhGH as it has been longed for many years in the pediatric endocrinology field.
PMID: 26683877
ISSN: 1662-2979
CID: 3568752