Arterial Platelet Adhesion in Atherosclerosis-Prone Arteries of Obese, Insulin-Resistant Nonhuman Primates.

Background Platelet-endothelial interactions are thought to contribute to early atherogenesis. These interactions are potentiated by oxidative stress. We used in vivo molecular imaging to test the hypothesis that platelet-endothelial interactions occur at early stages of plaque development in obese, insulin-resistant nonhuman primates, and are suppressed by NADPH-oxidase-2 inhibition.

Augmentation of Tissue Perfusion with Contrast Ultrasound: Influence of Three-Dimensional Beam Geometry and Conducted Vasodilation.

Background: Cavitation of microbubble contrast agents with ultrasound produces shear-mediated vasodilation and an increase in tissue perfusion. We investigated the influence of the size of the cavitation volume by comparing flow augmentation produced by two-dimensional (2D) versus three-dimensional (3D) therapeutic ultrasound. We also hypothesized that cavitation could augment flow beyond the ultrasound field through release of vasodilators that are carried downstream.

Echocardiographic Molecular Imaging of the Effect of Anticytokine Therapy for Atherosclerosis.

Background: Echocardiographic molecular imaging techniques are beginning to be applied to evaluate preclinical efficacy of new drugs. In a large clinical trial, anti-interleukin-1β (IL-1β) immunotherapy reduced atherosclerotic events, yet treatment effects were modest, and the mechanisms of action were not fully elucidated. We tested the hypothesis that echocardiographic molecular imaging can assess changes in vascular thromboinflammatory status in response to anti-IL-1β therapy.

Flow Augmentation in the Myocardium by Ultrasound Cavitation of Microbubbles: Role of Shear-Mediated Purinergic Signaling.

Background: Ultrasound-mediated cavitation of microbubble contrast agents produces high intravascular shear. We hypothesized that microbubble cavitation increases myocardial microvascular perfusion through shear-dependent purinergic pathways downstream from ATP release that is immediate and sustained through cellular ATP channels such as Pannexin-1.

Methods: Quantitative myocardial contrast echocardiography perfusion imaging and in vivo optical imaging of ATP was performed in wild-type and Pannexin-1-deficient (Panx1) mice before and 5 and 30 minutes after 10 minutes of ultrasound-mediated (1.

Ultrasound Molecular Imaging: Principles and Applications in Cardiovascular Medicine.

Purpose Of Review: Non-invasive molecular imaging is currently used as a research technique to better understand disease pathophysiology. There are also many potential clinical applications where molecular imaging may provide unique information that allows either earlier or more definitive diagnosis, or can guide precision medicine-based decisions on therapy. Contrast-enhanced ultrasound (CEU) with targeted microbubble contrast agents is one such technique that has been developed that has the unique properties of providing rapid information and revealing information only on events that occur within the vascular space.

Thrombotic microangiopathy as a cause of cardiovascular toxicity from the BCR-ABL1 tyrosine kinase inhibitor ponatinib.

The third-generation tyrosine kinase inhibitor (TKI) ponatinib has been associated with high rates of acute ischemic events. The pathophysiology responsible for these events is unknown. We hypothesized that ponatinib produces an endothelial angiopathy involving excessive endothelial-associated von Willebrand factor (VWF) and secondary platelet adhesion.

Myocardial Infarction Produces Sustained Proinflammatory Endothelial Activation in Remote Arteries.

Background: In the months after acute myocardial infarction (MI), risk for acute atherothrombotic events in nonculprit arteries increases several fold.

Objectives: This study investigated whether sustained proinflammatory and prothrombotic endothelial alterations occur in remote vessels after MI.

Methods: Wild-type mice, atherosclerotic mice with double knockout (DKO) of the low-density lipoprotein receptor and Apobec-1, and DKO mice treated with the Nox-inhibitor apocynin were studied at baseline and at 3 and 21 days after closed-chest MI.

Lipoprotein Apheresis Acutely Reverses Coronary Microvascular Dysfunction in Patients With Severe Hypercholesterolemia.

Objectives: This study evaluated whether lipoprotein apheresis produces immediate changes in resting perfusion in subjects with severe hypercholesterolemia, and whether there is a difference in the response between peripheral and coronary microcirculations.

Background: Lipoprotein apheresis is used in patients with severe hypercholesterolemia to reduce plasma levels of low-density lipoprotein cholesterol.

Methods: Quantitative contrast-enhanced ultrasound perfusion imaging of the myocardium at rest and skeletal muscle at rest and during calibrated contractile exercise was performed before and immediately after lipoprotein apheresis in 8 subjects with severe hypercholesterolemia, 7 of whom had a diagnosis of familial hypercholesterolemia.