👤 Polyxeni Manifava

National epidemiologic data are needed to inform country-specific healthcare policies for prevention and new developing treatments. We aimed to analyze Greek epidemiologic data in clinically relevant special populations for targeted treatments and to evaluate the utility of lipoprotein(a) [Lp(a)] as a risk enhancer METHODS: Two independent cohorts were included in this analysis: (1) consecutively recruited patients assessed in a tertiary outpatients' lipid clinic (Athens Angiometabolic cohort [AAC], n = 1106) with available peripheral vascular markers, and (2) sample of the Greek general population (ATTICA study [AS], n = 2682) with available 20-year follow-up data for atherosclerotic cardiovascular disease (ASCVD) events. Increased Lp(a) was found in 8.3% of the AS (≥50 mg/dL) and in 18.9% of the AAC (≥125 nmol/L) (16.0% without ASCVD and 22.1% with ASCVD, P = .006). Elevated Lp(a) levels were associated with increased carotid, coronary artery, and lower extremity atherosclerosis (P < .05 for all). Both the European Atherosclerosis Society (EAS) recommendations (net reclassification index [NRI]: 0.170) and a derived sex-specific inflation factor for HellenicSCOREII+ (NRI: 0.176) were efficient in incorporating Lp(a) as a risk enhancer over HellenicSCOREII+ for 20-year major adverse cardiovascular events. For 10-year cardiovascular death, only the EAS consensus provided significant reclassification. Finally, Lp(a) conferred increased eligibility for more aggressive primary prevention measures both by EAS recommendations (23.6% in AAC/13.6% in AS) and by sex-specific inflation factors (25.6% in AAC/22.3% in AS). Elevated Lp(a) levels were observed in 8.3% of the general population cohort and up to 23.9% in participants with ASCVD from the lipid clinic cohort, highlighting a risk gradient across ASCVD categories. Incorporating Lp(a) as a risk enhancer improves ASCVD risk reclassification beyond the validated HellenicSCOREII+. Show less

During macroautophagy/autophagy, the ULK complex nucleates autophagic precursors, which give rise to autophagosomes. We analyzed, by live imaging and mathematical modeling, the translocation of ATG13 (part of the ULK complex) to the autophagic puncta in starvation-induced autophagy and ivermectin-induced mitophagy. In nonselective autophagy, the intensity and duration of ATG13 translocation approximated a normal distribution, whereas wortmannin reduced this effect and shifted to a log-normal distribution. During mitophagy, multiple translocations of ATG13 with increasing time between peaks were observed. We hypothesized that these multiple translocations arise because the engulfment of mitochondrial fragments required successive nucleation of phagophores on the same target, and a mathematical model based on this idea reproduced the oscillatory behavior. Significantly, model and experimental data were also in agreement that the number of ATG13 translocations is directly proportional to the diameter of the targeted mitochondrial fragments. Thus, our data provide novel insights into the early dynamics of selective and nonselective autophagy. Show less