Design and rationale of a randomized clinical trial assessing the effect of inclisiran on atherosclerotic plaque in individuals without previous cardiovascular event and without flow- limiting lesions identified in an in-hospital screening: The VICTORION-PLAQUE primary prevention trial.

Background: The impact of low-density lipoprotein cholesterol (LDL-C) on atherosclerotic cardiovascular disease (ASCVD) risk is influenced by both the magnitude and duration of exposure. Patients with nonobstructive coronary artery disease (NOCAD) and a CT-adapted Leaman score (CT-LeSc) >5 have a higher risk of cardiac events. The CT-LeSc semi-quantitatively assesses total coronary atherosclerotic burden via coronary computed tomography angiography (CCTA).

Long-term efficacy and safety of inclisiran in patients with high cardiovascular risk and elevated LDL cholesterol (ORION-3): results from the 4-year open-label extension of the ORION-1 trial.

Introduction: Whether long-term treatment with the twice-yearly, siRNA therapeutic inclisiran, which reduces hepatic production of proprotein convertase subtilisin/kexin type 9 (PCSK9), results in sustained reductions in LDL cholesterol with an acceptable safety profile is not known. The aim of this study was to assess the effect of long-term dosing of inclisiran in patients with high cardiovascular risk and elevated LDL cholesterol.

Methods: ORION-3 was a 4-year open-label extension study of the placebo-controlled, phase 2 ORION-1 trial, conducted at 52 sites across five countries.

LDL phenotype in subjects with mild cognitive impairment and Alzheimer's disease.

Background: Centenarians with normal cognitive function have a "longevity phenotype" characterized by large low-density lipoproteins (LDL) and high-density lipoproteins (HDL) and low incidence of metabolic syndrome, hypertension, and cognitive impairment. Alzheimer's disease (AD) is associated with a number of cardiovascular risk factors, but it is not known if they have or lack the "longevity phenotype".

Objective: The study was designed to determine LDL size and body fat content and distribution in subjects with mild cognitive impairment (MCI) and AD.

Plexins are GTPase-activating proteins for Rap and are activated by induced dimerization.

Plexins are cell surface receptors that bind to semaphorins and transduce signals that regulate neuronal development, immune responses, and other processes. Signaling through plexins has been proposed to rely on specific guanosine triphosphatase (GTPase)-activating protein (GAP) activity for R-Ras and M-Ras. Activation of this GAP activity of plexins appears to require simultaneous binding of semaphorin to the plexin extracellular domain and of the Rho GTPases Rac1 or Rnd1 to the cytoplasmic region.