Disturbed Laminar Blood Flow Vastly Augments Lipoprotein Retention in the Artery Wall: A Key Mechanism Distinguishing Susceptible From Resistant Sites.

Objective: Atherosclerosis develops initially at branch points and in areas of high vessel curvature. Moreover, experiments in hypercholesterolemic mice have shown that the introduction of disturbed flow in straight, atherosclerosis-resistant arterial segments turns them highly atherosclerosis susceptible. Several biomechanical mechanisms have been proposed, but none has been demonstrated.

Induction of atherosclerosis in mice and hamsters without germline genetic engineering.

Rationale: Atherosclerosis can be achieved in animals by germline genetic engineering, leading to hypercholesterolemia, but such models are constrained to few species and strains, and they are difficult to combine with other powerful techniques involving genetic manipulation or variation.

Objective: To develop a method for induction of atherosclerosis without germline genetic engineering.

Methods And Results: Recombinant adeno-associated viral vectors were engineered to encode gain-of-function proprotein convertase subtilisin/kexin type 9 mutants, and mice were given a single intravenous vector injection followed by high-fat diet feeding.

Wall shear stress and local plaque development in stenosed carotid arteries of hypercholesterolemic minipigs.

Background: Wall shear stress is thought to play a critical role in the local development of atherosclerotic plaque and to affect plaque vulnerability. However, current models and hypotheses do not fully explain the link between wall shear stress and local plaque development. We aimed to investigate the relation between wall shear stress and local plaque development in surgically induced common carotid artery stenoses of hypercholesterolemic minipigs.

Oversized vein grafts develop advanced atherosclerosis in hypercholesterolemic minipigs.

Background: Accelerated atherosclerosis is the main cause of late aortocoronary vein graft failure. We aimed to develop a large animal model for the study of pathogenesis and treatment of vein graft atherosclerosis.

Methods: An autologous reversed jugular vein graft was inserted end-to-end into the transected common carotid artery of ten hypercholesteroemic minipigs.

Familial hypercholesterolaemic downsized pig with human-like coronary atherosclerosis: a model for preclinical studies.

Aims: A manageable and reproducible large animal model of human-like coronary atherosclerosis is lacking but highly needed for translational research in percutaneous coronary interventions and imaging. Farm pigs with familial hypercholesterolaemia develop advanced atherosclerosis in two to three years but then weigh >200 kg making them impractical and costly. We aimed at down-sizing this pig and accelerating coronary plaque development to make the model more useful and affordable.

Unreliable assessment of necrotic core by virtual histology intravascular ultrasound in porcine coronary artery disease.

Background: Intravascular ultrasound-derived virtual histology (VH IVUS) is used increasingly in clinical research to assess composition and vulnerability of coronary atherosclerotic lesions. However, the ability of VH IVUS to quantify individual plaque components, in particular the size of the destabilizing necrotic core, has never been validated. We tested for correlation between VH IVUS necrotic core size and necrotic core size by histology in porcine coronary arteries with human-like coronary disease.