A modified provisional stenting approach to coronary bifurcation lesions: clinical application of the "jailed-balloon technique".

Objectives: To demonstrate the application of a novel provisional side branch (SB) stenting strategy for coronary bifurcation lesions using a "jailed-balloon" technique (JBT).

Background: Adverse cardiac events are higher for percutaneous coronary intervention (PCI) of bifurcation lesions. Recent studies support the use of provisional SB stenting, but a risk of SB closure and a higher rate of target lesion revascularization (TLR) remain important limitations.

Nanotechnology in interventional cardiology.

High-grade atherosclerotic stenoses are reduced to zero or minimal residual stenosis grades by a single or a series of balloon angioplasties. Currently, stents are implanted to prevent immediate vascular recoil and elution of an antimitotic drug from the stent struts minimizes restenosis. An unwanted side-effect of this drug elution is delayed re-endothelialization which requires treatment with two anti-platelet drugs, in many cases for a minimum of 1 year to prevent acute in-stent thrombosis.

Use of mechanical assist during high-risk PCI and STEMI with cardiogenic shock.

Infarct size may be reduced by left ventricular unloading after ST-segment elevation MI (STEMI) in addition to reperfusion therapy. Likewise, high-risk percutaneous coronary intervention (PCI) may benefit from periprocedural support especially in patients with low cardiac output at baseline or when periprocedural hemodynamic deterioration is anticipated. Traditionally, intraaortic balloon-pumps have been used in acute MI with cardiogenic shock.

Anti-angiogenic perfluorocarbon nanoparticles for diagnosis and treatment of atherosclerosis.

Complementary developments in nanotechnology, genomics, proteomics, molecular biology and imaging offer the potential for early, accurate diagnosis. Molecularly-targeted diagnostic imaging agents will allow noninvasive phenotypic characterization of pathologies and, therefore, tailored treatment close to the onset. For atherosclerosis, this includes anti-angiogenic therapy with specifically-targeted drug delivery systems to arrest the development of plaques before they impinge upon the lumen.

Expression of thromboxane synthase, prostacyclin synthase and thromboxane receptor in atherosclerotic lesions: correlation with plaque composition.

Objectives: Prostaglandins, such as thromboxane A(2) (TxA(2)) and prostacyclin (PGI(2)), are bioactive lipid mediators that are implicated in the pathogenesis of atherosclerosis. In the current study, we tested the hypothesis that thromboxane synthase (TXAS), prostacyclin synthase (PGIS) and thromboxane receptor (TP) are expressed within the atherosclerotic lesion.

Methods: Atherosclerotic aorta segments were obtained from low-density lipoprotein receptor deficient (LDL r-KO) mice on a high fat diet.

Coronary CT angiography (CCTA) and advances in CT plaque imaging.

The goal of this review is to highlight current advances in the non-invasive detection of clinically significant atherosclerotic disease including the so-called vulnerable plaque with computed tomography. Atherosclerotic disease encompasses stages of plaque progression, stabilization, and even regression. Traditionally, the focus of diagnostic imaging has been the detection of lumen-occluding atheroma.

Intramural delivery of rapamycin with alphavbeta3-targeted paramagnetic nanoparticles inhibits stenosis after balloon injury.

Background: Drug eluting stents prevent vascular restenosis but can delay endothelial healing. A rabbit femoral artery model of stenosis formation after vascular injury was used to study the effect of intramural delivery of alpha(v)beta(3)-integrin-targeted rapamycin nanoparticles on vascular stenosis and endothelial healing responses.

Methods And Results: Femoral arteries of 48 atherosclerotic rabbits underwent balloon stretch injury and were locally treated with either (1) alpha(v)beta(3)-targeted rapamycin nanoparticles, (2) alpha(v)beta(3)-targeted nanoparticles without rapamycin, (3) nontargeted rapamycin nanoparticles, or (4) saline.

Clinical applications of perfluorocarbon nanoparticles for molecular imaging and targeted therapeutics.

Molecular imaging is a novel tool that has allowed non-invasive diagnostic imaging to transition from gross anatomical description to identification of specific tissue epitopes and observation of biological processes at the cellular level. This technique has been confined to the field of nuclear imaging; however, recent advances in nanotechnology have extended this research to include ultrasound (US) and magnetic resonance (MR) imaging. The exploitation of nanotechnology for MR and US molecular imaging has generated several candidate contrast agents.

Molecular imaging by cardiovascular MR.

Do molecularly-targeted contrast agents have what it takes to usher in a paradigm shift as to how we will image cardiovascular disease in the near future? Moreover, are non-invasive vulnerable plaque detection and preemptive treatments with these novel nanoparticulate agents within reach for clinical applications? In this article, we attempt to make a compelling case for how the advent of molecularly-targeted nanoparticle technology may change the way we detect atherosclerotic lesions, determine their clinical significance and even provide non-invasive treatments. Focusing on imaging with cardiovascular MR, an overview of the latest developments in this rapidly evolving field of so-called "intelligent" contrast agents that are able to interrogate the vascular wall and various complementary advanced imaging technologies are presented.

Nanomedicine opportunities for cardiovascular disease with perfluorocarbon nanoparticles.

Nanomedicine promises to enhance the ability of clinicians to address some of the serious challenges responsible for cardiovascular mortality, morbidity and numerous societal consequences. Targeted imaging and therapy applications with perfluorocarbon nanoparticles are relevant to a broad spectrum of cardiovascular diseases, ranging from asymptomatic atherosclerotic disease to acute myocardial infarction or stroke. As illustrated in this article, perfluorocarbon nanoparticles offer new tools to recognize and characterize pathology, to identify and segment high-risk patients and to treat chronic and acute disease.

A novel thromboxane receptor antagonist and synthase inhibitor, BM-573, reduces development and progression of atherosclerosis in LDL receptor deficient mice.

Atherosclerosis is a chronic inflammatory disease of the vasculature influenced by a variety of mediators. Among them, prostanoids, which include prostacyclin and thromboxane (Tx) A(2), have recently received a lot of attention. Previous studies demonstrated that antagonism or deletion of the receptor for TxA(2) retards early atherogenesis in apolipoprotein E-deficient mice, but no data are available in low-density lipoprotein (LDL) receptor deficient mice.

Thromboxane receptor blockade improves the antiatherogenic effect of thromboxane A2 suppression in LDLR KO mice.

Suppression of thromboxane (Tx) A(2) biosynthesis retards atherogenesis. In this setting, the coincidental presence of nonconventional ligands for the TxA(2) receptor (TP), such as isoprostanes, could still induce a proatherogenic vascular phenotype. However, no data are available on the effect of combining suppression of TxA(2) formation with blockade of TP in atherogenesis.

Nanomedicine opportunities in cardiology.

Despite myriad advances, cardiovascular-related diseases continue to remain our greatest health problem. In more than half of patients with atherosclerotic disease, their first presentation to medical attention becomes their last. Patients often survive their first cardiac event through acute revascularization and placement of drug-eluting stents (DES), but only select coronary lesions are amenable to DES placement, resulting in the use of bare metal or no stent, both of which lack the benefit of antirestenotic therapy.

MR three-dimensional molecular imaging of intramural biomarkers with targeted nanoparticles.

In this study, porcine carotid arteries were subjected to balloon overstretch injury followed by local delivery of paramagnetic nanoparticles targeted to alphavbeta3-integrin expressed by smooth muscle cells or collagen III within the extracellular matrix. Carotid T1-weighted angiography and vascular imaging was performed at 1.5T.

Stabilization of advanced atherosclerosis in low-density lipoprotein receptor-deficient mice by aspirin.

COX-1-dependent eicosanoid formation accelerates atherogenesis, and low-dose aspirin reduces early atherosclerosis. However, the role of aspirin in modulating progression of vascular atherosclerotic lesions once established is less investigated. We wished to determine the effect of low-dose aspirin on vascular inflammation, plaque composition, and progression of established atherosclerosis.

Involvement of thromboxane receptor in the proatherogenic effect of isoprostane F2alpha-III: evidence from apolipoprotein E- and LDL receptor-deficient mice.

Background: Atherosclerosis is a chronic inflammatory disease of the arterial wall, where it associates with oxidative stress and formation of oxidized lipids. The lipid oxidation product isoprostane iPF2alpha-III, also known as 8-isoPGF2alpha and 15-F2t-IsoP, is elevated in patients with cardiovascular disease and present in atherosclerotic lesions. Several proatherogenic biological effects have been attributed to this isoprostane, suggesting that it could be an active factor in the pathogenesis of the disease.

Magnetic resonance nanoparticles for cardiovascular molecular imaging and therapy.

Molecular vascular imaging represents a novel tool that promises to change the current medical paradigm of 'see and treat' to a 'detect and prevent' strategy. Nanoparticle agents, such as superparamagnetic nanoparticles and perfluorocarbon nanoparticle emulsions, have been developed for noninvasive imaging, particularly for magnetic resonance imaging. Designed to target specific epitopes in tissues, these agents are beginning to enter clinical trials for cardiovascular applications.

Vitamin E reduces progression of atherosclerosis in low-density lipoprotein receptor-deficient mice with established vascular lesions.

Background: A growing body of evidence from animal studies supports the hypothesis that oxidative stress-mediated mechanisms play a central role in early atherogenesis. In contrast, clinical trials with antioxidant vitamins have not produced consistent results in humans with established atherosclerosis.

Methods And Results: Low-density lipoprotein receptor-deficient mice (LDLR KO) were fed a high-fat diet for 3 months to induce atheroma.

Effect of low-dose aspirin on vascular inflammation, plaque stability, and atherogenesis in low-density lipoprotein receptor-deficient mice.

Background: Atherosclerosis is a complex vascular inflammatory disease. Low-dose aspirin is a mainstay in the prevention of vascular complications of atherosclerosis. We wished to determine the effect of low-dose aspirin on vascular inflammation, plaque composition, and atherogenesis in LDL receptor-deficient mice fed a high fat diet.

Selective interleukin-12 synthesis defect in 12/15-lipoxygenase-deficient macrophages associated with reduced atherosclerosis in a mouse model of familial hypercholesterolemia.

Targeted gene disruption or overexpression of 12/15-lipoxygenase in mice on the genetic background of apolipoprotein E or low density lipoprotein-receptor (LDL-R) deficiency has implicated 12/15-lipoxygenase in atherogenesis. The data support indirectly a role for 12/15-lipoxygenase in the oxidative modification of low density lipoprotein. In this study we set out to explore other potential mechanisms for 12/15-lipoxygenase in atherosclerosis using apolipoprotein B mRNA editing catalytic polypeptide-1/LDL-R double-deficient mice, a model highly related to the human condition of familial hypercholesterolemia.