👤 Stephany El Hayek

Atherosclerotic cardiovascular disease (CVD) remains a leading cause of vascular disease worldwide. Atherosclerosis is characterized by the accumulation of lipids and oxidized lipids on the blood vessel walls. Coronary artery disease (CAD) is the most common display of atherosclerotic CVD. We investigated the effects of the bioactive lipids as lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS (20,5,0)) and its derivative oleoyl-N-trimethyl homoserine amide (oleoyl amide-MHS) on the properties and functionality of HDL and paraoxonase 1 (PON1) activities in the serum of individuals who exhibited arterial plaque as observed by coronary CT angiography (CCTA). The study included two independent groups comprising 40 patients who had undergone arterial CCTA scans at Ziv Medical Center for various medical indications. The CAD group included 20 patients with coronary artery plaques with luminal stenosis of more than 50 % in a major coronary vessel. The control group consisted of 20 healthy patients (patients without artery plaques). Serum samples from CAD patients exhibited lower serum PON1 and cholesterol efflux activities and higher pro-inflammatory than the control group. HDL isolated from CAD patients contains elevated levels of oxidizing lipids (specifically lyso- phosphatidyl ethanolamines and lyso-phosphocholines(compared to the control. However, incubation of the CAD patients' serum with lyso-DGTS and oleoyl amide-MHS restored the antiatherogenic activities of HDL. The lipids increased serum PON1 activities, enhanced apoB-depleted serum cholesterol-efflux activity, and elevated the serum's anti-inflammatory properties. The results of the present study suggest the potential of the bioactive lipids lyso-DGTS and oleoyl amide-MHS to attenuate atherosclerosis via the improvement of dysfunctional HDL properties and PON1 activities. Further, in-vivo experiments are needed to assess the athero-protective effect of the lipids. Show less

Clinical and molecular data on the occurrence and frequency of inherited neuromuscular disorders (NMD) in the Lebanese population is scarce. This study aims to provide a retrospective overview of hereditary NMDs based on our clinical consultations in Lebanon. Clinical and molecular data of patients referred to a multi-disciplinary consultation for neuromuscular disorders over a 20-year period (1999-2019) was reviewed. A total of 506 patients were diagnosed with 62 different disorders encompassing 10 classes of NMDs. 103 variants in 49 genes were identified. In this cohort, 81.4% of patients were diagnosed with motor neuron diseases and muscular dystrophies, with almost half of these described with spinal muscular atrophy (SMA) (40.3% of patients). We estimate a high SMA incidence of 1 in 7,500 births in Lebanon. Duchenne and Becker muscular dystrophy were the second most frequently diagnosed NMDs (17% of patients). These disorders were associated with the highest number of variants (39) identified in this study. A highly heterogeneous presentation of Limb Girdle Muscular Dystrophy and Charcot-Marie-Tooth disease was notably identified. The least common disorders (5.5% of patients) involved congenital, metabolic, and mitochondrial myopathies, congenital myasthenic syndromes, and myotonic dystrophies. A review of the literature for selected NMDs in Lebanon is provided. Our study indicates a high prevalence and underreporting of heterogeneous forms of NMDs in Lebanon- a major challenge with many novel NMD treatments in the pipeline. This report calls for a regional NMD patient registry. Show less

A role for inflammation and oxidative stress is reported in autism spectrum disorders (ASDs). Here, we tested possible changes in expression and/or oxidative status for plasma proteins in subjects with ASDs. To evaluate protein expression and protein adducts of lipid peroxidation-derived aldehyde, analysis of plasma proteins was performed in 30 subjects with ASDs and compared with 30 healthy controls with typical development, using a proteomic approach. Significant changes were evidenced for a total of 12 proteins. Of these, ten were identified as proteins involved in the acute inflammatory response including alpha-2-macroglobulin, alpha-1-antitrypsin, haptoglobin, fibrinogen, serum transferrin, prealbumin, apolipoprotein A-I apolipoprotein A-IV, apolipoprotein J, and serum albumin. In addition, significant changes occurred for two immunoglobulins alpha and gamma chains. Our present data indicate that an inflammatory response, coupled with increased lipid peroxidation, is present in subjects with ASDs. This information can provide new insight into the identification of potential plasma protein biomarkers in autism. Show less

Sequence variants affecting blood lipids and coronary artery disease (CAD) may enhance understanding of the atherogenicity of lipid fractions. Using a large resource of whole-genome sequence data, we examined rare and low-frequency variants for association with non-HDL cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides in up to 119,146 Icelanders. We discovered 13 variants with large effects (within ANGPTL3, APOB, ABCA1, NR1H3, APOA1, LIPC, CETP, LDLR, and APOC1) and replicated 14 variants. Five variants within PCSK9, APOA1, ANGPTL4, and LDLR associate with CAD (33,090 cases and 236,254 controls). We used genetic risk scores for the lipid fractions to examine their causal relationship with CAD. The non-HDL cholesterol genetic risk score associates most strongly with CAD (P = 2.7 × 10(-28)), and no other genetic risk score associates with CAD after accounting for non-HDL cholesterol. The genetic risk score for non-HDL cholesterol confers CAD risk beyond that of LDL cholesterol (P = 5.5 × 10(-8)), suggesting that targeting atherogenic remnant cholesterol may reduce cardiovascular risk. Show less