👤 Heather A Renna

Lipoprotein(a) [Lp(a)] is a genetically determined and independent cardiovascular risk factor. Despite its clinical relevance, data on Lp(a) prevalence and impact in Latin America are limited. We aimed to assess the prevalence of elevated Lp(a) and its association with cardiovascular outcomes in a large, multicenter Argentine registry. The GAELp(a) registry included 3000 adults from six Argentine regions. Lp(a) levels were measured using standardized assays; elevated Lp(a) was defined as >50 mg/dL or >125 nmol/L. Clinical, biochemical, and imaging data were collected retrospectively and prospectively. Associations between Lp(a) and major adverse cardiovascular events (MACE) were evaluated with logistic regression in the overall population and stratified by statin use. Elevated Lp(a) was present in 31.4 % of participants, with no sex difference. It was associated with family history of cardiovascular disease, subclinical atherosclerosis, and familial hypercholesterolemia. Patients with elevated Lp(a) had a higher prevalence of coronary artery disease (18.4 % vs. 12.5 %, p < 0.001), peripheral artery disease (4.8 % vs. 2.5 %, p = 0.001), and MACE (21.3 % vs. 14.8 %, p < 0.001). Elevated Lp(a) independently predicted MACE (OR 1.53, 95 % CI: 1.24-1.90, p < 0.001), with stronger associations in statin-naïve individuals (OR 2.18, 95 % CI: 1.17-4.07). ROC analysis showed modest discrimination (AUC 0.57 in nmol/L, 0.59 in mg/dL). Elevated Lp(a) is frequent in Argentina and strongly linked to cardiovascular disease and events. Its predictive value appears greater in statin-naïve patients, highlighting its role as a marker of residual risk. These findings support routine Lp(a) measurement in cardiovascular risk assessment, particularly in regions with high ASCVD burden. Show less

Nilotinib, a tyrosine kinase inhibitor that targets the Abelson tyrosine kinase (c-Abl) signaling pathway, is FDA-approved to treat chronic myeloid leukemia. Nilotinib has properties indicative of a possible utility in neuroprotection that have prompted exploration of repurposing the drug for the treatment of Alzheimer's disease (AD) and Parkinson's disease (PD). AD is a progressive age-related neurodegenerative disorder characterized by the deposition of extracellular amyloid-β plaques and intracellular neurofibrillary tangles. It is incurable and affects approximately 50 million patients worldwide. Nilotinib reduces c-Abl phosphorylation, amyloid-β levels, and dopaminergic neuron degeneration in preclinical AD models. This study explores the effects of nilotinib on amyloid processing and mitochondrial functioning in the SH-SY5Y human neuroblastoma cell line. SH-SY5Y cells were exposed to nilotinib (1, 5, and 10 µM). Real-time PCR and immunoblot analysis were performed to quantify the expression of genes pertaining to amyloid-β processing and neuronal health. Nilotinib did not significantly change APP, BACE1, or ADAM10 mRNA levels. However, BACE1 protein was significantly increased at 1 µM, and ADAM10 was increased at 10 µM nilotinib without affecting APP protein expression. Further, nilotinib treatment did not affect the expression of genes associated with neuronal health and mitochondrial functioning. Taken together, our findings do not support the efficacy of nilotinib treatment for neuroprotection. Show less

Mitochondrial degeneration in various neurodegenerative diseases, specifically in Alzheimer's disease, involves excessive mitochondrial fission and reduced fusion, leading to cell damage. P110 is a seven-amino acid peptide that restores mitochondrial dynamics by acting as an inhibitor of mitochondrial fission. However, the role of P110 as a neuroprotective agent in AD remains unclear. Therefore, we performed cell culture studies to evaluate the neuroprotective effect of P110 on amyloid-β accumulation and mitochondrial functioning. Human SH-SY5Y neuronal cells were incubated with 1 µM and 10 µM of P110, and Real-Time PCR and Western blot analysis were done to quantify the expression of genes pertaining to AD and neuronal health. Exposure of SH-SY5Y cells to P110 significantly increased APP mRNA levels at 1 µM, while BACE1 mRNA levels were increased at both 1 µM and 10 µM. However, protein levels of both APP and BACE1 were significantly reduced at 10 µM of P110. Further, P110 treatment significantly increased ADAM10 and Klotho protein levels at 10 µM. In addition, P110 exposure significantly increased active mitochondria and reduced ROS in live SH-SY5Y cells at both 1 µM and 10 µM concentrations. Taken together, our results indicate that P110 might be useful in attenuating amyloid-β generation and improving neuronal health by maintaining mitochondrial function in neurons. Show less