Detection of Ceramide, a Risk Factor for Coronary Artery Disease, in Human Coronary Plaques by Fluorescent Angioscopy.

Background: The presence of ceramide in human coronary plaques is a risk factor for ischemic heart disease, but its visualization in the human vessel wall is currently beyond the scope of any available imaging techniques.

Methods and results: Deposition of ceramide was examined by fluorescent angioscopy (FA) and microscopy (FM) using golden fluorescence (Go) as a specific marker of ceramide in yellow plaques, which were obtained from 23 autopsy subjects and classified by conventional angioscopy and histology. Ceramide was observed by FM in 34 of the 41 yellow plaques with a necrotic core (NC) but rarely in the 28 without.

Imaging of Triglycerides in Human Coronary Plaques by Color Fluorescent Angioscopy and Microscopy.

Native triglycerides (TG) deposited in the human vascular wall is not measurable or visible in vivo to date. We discovered that by exciting fluorescence at 345 nm and emitting at 420 nm, 3-amino-4-hydroxy-5-nitrobenzene sulfonic acid monohydrate (3-ANA) elicits a brown fluorescence that is characteristic of just TG. Therefore, localization of TG in coronary plaques and normal segments that were obtained from 19 human autopsy cases was examined by color fluorescent angioscopy (CFA) and microscopy using 3-ANA as a biomarker of TG.

Human pericoronary adipose tissue as storage and possible supply site for oxidized low-density lipoprotein and high-density lipoprotein in coronary artery.

Background: Thickening of the pericoronary adipose tissue (PCAT) is a proven risk factor for coronary artery disease, but it is poorly understood whether PCAT stores pro-atherogenic substances with oxidized low-density lipoprotein (oxLDL) and low-density lipoprotein (LDL), and an anti-atherogenic substance with high-density lipoprotein (HDL) and supply them to the coronary intima.

Methods: Using immunohistochemical techniques, the localization of oxLDL, LDL and HDL in PCAT and its adjacent coronary segments was examined in 30 epicardial coronary arteries excised from 11 human autopsy cases.

Results: PCAT stored oxLDL and HDL in all, but LDL rarely, in 77 specimens examined, irrespective of the presence or absence of coronary plaques and underlying disease.

Pericoronary Adipose Tissue as Storage and Supply Site for Oxidized Low-Density Lipoprotein in Human Coronary Plaques.

Objectives: It is generally believed that low-density lipoprotein enters the vascular wall from its lumen and oxidized (oxLDL), after which it plays an important role in atherosclerosis. Because voluminous epicardial adipose tissue is a risk factor for coronary events, there is a possibility that the pericoronary adipose tissue (PCAT), which is a part of epicardial adipose tissue, acts as a risk factor by supplying oxLDL to the coronary arterial wall. The present study was performed whether PCAT stores and supplies oxLDL to the coronary wall.

Molecular Imaging of Native Low-Density Lipoprotein by Near-Infrared Fluorescent Angioscopy in Human Coronary Plaques.

Low-density lipoprotein (LDL) is an important risk factor for coronary artery disease, but its localization within the human coronary arterial wall is poorly understood. Imaging of LDL in 30 coronary arteries excised from 15 subjects who underwent autopsy was performed using near-infrared fluorescent angioscopy system and using indocyanine green dye as a biomarker of LDL. The percentage incidence of LDL in 28 normal segments, 24 white plaques (early stage of plaque growth), and 21 yellow plaques (mature stage of plaque) classified by conventional angioscopy, was 14.

Dye-Staining Angioscopy for Coronary Artery Disease.

Novel imaging techniques using biomarkers have clarified the mechanisms of hitherto unanswered or misunderstood phenomena of coronary artery disease and enabled evaluation of myocardial blood and tissue fluid flows in vivo. Dye-staining coronary angioscopy using Evans blue (EB) as the biomarker can visualize fibrin and damaged endothelial cells, revealing that the so-called platelet thrombus is frequently a fibrin-rich thrombus; occlusive transparent fibrin thrombus, but not platelet thrombus, is not infrequently a cause of acute coronary syndrome; "fluffy" coronary luminal surface is caused by fibrin threads arising from damaged endothelial cells and is a residue of an occlusive thrombus after autolysis in patients with acute coronary syndrome without angiographically demonstrable coronary stenosis; and web or membrane-like fibrin thrombus is a cause of stent edge restenosis. Fluorescent angioscopy using visual or near-infrared light wavelengths is now used clinically for molecular imaging of the substances such as lipoproteins and cholesterol that constitute coronary plaques.

Imaging of native high-density lipoprotein in human coronary plaques by color fluorescent angioscopy.

Background: High-density lipoprotein (HDL) plays a key role in reverse cholesterol transport, and halts the progression of atherosclerosis. The aim of the present study was to visualize native HDL in the human coronary arterial wall.

Methods And Results: The fluorescence characteristics of HDL were investigated by color fluorescent microscopy (CFM) using excitation at 470 nm and emission at 515 nm with Fast green dye (FG) as the biomarker.

Localization of native high-density lipoprotein and its relation to plaque morphology in human coronary artery.

High-density lipoprotein (HDL) plays a key role in reverse cholesterol transport, and halts the progression of atherosclerosis. However, its localization in human vascular wall is not well understood. We discovered that by exciting at 470-nm and emitting at 515-nm light wavelengths, Fast green dye (FG) elicits brown fluorescence characteristic of HDL only.

Smooth muscle-like cells resident in the media participate in spasm-induced coronary intimal hyperplasia.

Background: Coronary intimal hyperplasia occurs at the site of spasm in patients with vasospastic angina. The migration of vascular smooth muscle cells (VSMCs) from the media has been proposed as a potential mechanism; however, this has not been confirmed with supportive evidence.

Objective: To determine which cell types participate in spasm-induced coronary intimal hyperplasia.

Molecular imaging of apolipoprotein B-100 in human coronary plaques by color fluorescent angioscopy and microscopy.

Apolipoprotein B-100 (ApoB-100) is an important risk factor for coronary artery disease. However, its localization in human coronary plaques is not well understood. The present study was performed to visualize ApoB-100 in human coronary artery wall.

Impact of diabetes on long term follow-up of elderly patients with chronic total occlusion post percutaneous coronary intervention.

Background: The prognosis of elderly patients with chronic total occlusion (CTO) and diabetes mellitus (DM) treated with percutaneous coronary intervention (PCI) is not known.

Objective: To investigate the effect of diabetes on long-term follow-up of CTO after PCI in elderly patients.

Methods: A total of 153 elderly patients (age > 65 years old) with CTO lesions which were successfully treated with PCI were enrolled.

Localization of oxidized low-density lipoprotein and its relation to plaque morphology in human coronary artery.

Objectives: Oxidized low-density lipoprotein (oxLDL) plays a key role in the formation of atherosclerotic plaques. However, its localization in human coronary arterial wall is not well understood. The present study was performed to visualize deposition sites and patterns of native oxLDL and their relation to plaque morphology in human coronary artery.

Molecular imaging of low-density lipoprotein in human coronary plaques by color fluorescent angioscopy and microscopy.

Objectives: Low-density lipoprotein (LDL) is an important risk factor for coronary artery disease. However, its localization in human coronary plaques is not well understood. The present study was performed to visualize LDL in human coronary artery wall.

Migration of mononuclear cells expressing β-actin through the adventitia into media and intima in coronary arteriogenesis and venogenesis in ischemic myocardium.

It was previously thought that arteriogenesis and venogenesis are induced not only by proliferation of vessel-resident smooth muscle cells (SMCs) and endothelial cells (ECs) but also by migration of their precursors. However, it is not well understood through what route(s) the precursors migrate into the existing vessels.We examined through what route or routes circulating mononuclear cells expressing β-actin (β-MNCs), which we identified in canine coronary vessels, migrate into coronary vessel walls and cause arteriogenesis and venogenesis at 1, 2, 4 and 8 weeks after induction of myocardial infarction.

β-actin-positive mononuclear cells participate in coronary microvascular medial hyperplasia by migrating through adventitia into media, with special reference to microvessel angina.

Coronary microvascular hyperplasia is a cause of microvessel angina, although the underlying cellular mechanisms remain unclear. We examined how mononuclear cells expressing β-actin (β-MNCs), which were identified in coronary vessels, induce coronary microvascular hyperplasia.The presence of β-MNCs in coronary hyperplastic arterial (HAM) and venous microvessels (HVM) was examined by endomyocardial biopsy in 25 patients with suspected microvessel angina.

Nitroglycerin-induced heterogeneous subendocardial myocardial blood flow observed by cardioscopy in patients with coronary artery disease.

It is controversial as to whether or not nitroglycerin (NTG) increases subendocardial myocardial blood flow (SMBF), and if it does, whether arterial or venous blood flow is increased in patients with coronary artery disease. This study was performed to examine NTG-induced changes in SMBF.Changes in SMBF induced by NTG (200 µg, i.

Cardioscopic observation of subendocardial microvessels in patients with coronary artery disease.

Coronary microvessels play a direct and critical role in determining the extent and severity of myocardial ischemia and cardiac function. However, because direct observation has never been performed in vivo, the functional properties of the individual microvesssels in patients with coronary artery disease remain unknown. Subendocardial coronary microvessels were observed by cardioscopy in 149 successive patients with coronary artery disease (81 with stable angina and 68 with old myocardial infarction).

Cardioscopic detection of left ventricular thrombi. -With special reference to a comparison with left ventriculography and echocardiography-.

Background: Thrombosis occurs in the left ventricle and causes ischemic cerebral attacks. However, differences in the incidence of left ventricular thrombi (LVT) among various categories of heart diseases are not known.

Methods And Results: From April 2000 to 31 March 2008, 258 patients (104 females and 154 males; age 63 ± 6 years) with a heart disease underwent cardioscopy of the left ventricle.

Role of calcium-activated potassium channels in the genesis of 3,4-diaminopyridine-induced periodic contractions in isolated canine coronary artery smooth muscles.

We found that 3,4-diaminopyridine (3,4-DAP), a voltage-gated potassium channel (K(V)) inhibitor, elicits pH-sensitive periodic contractions (PCs) of coronary smooth muscles. Underlying mechanisms of PCs, however, remained to be elucidated. The present study was performed to examine the roles of ion channels in the genesis of PCs.

Histological characteristics of glistening yellow coronary plaques seen on angioscopy. -With special reference to vulnerable plaques-.

Background: Glistening yellow coronary plaques (GY) seen on angioscopy are considered vulnerable to disruption. Collagen fiber (CF) is the main substance that protects coronary plaques against mechanical stress. Therefore, whether angioscopically defined vulnerable plaques correlate with those defined histologically was investigated.

Characterization of coronary fibrin thrombus in patients with acute coronary syndrome using dye-staining angioscopy.

Objective: Because fibrin is transparent and almost invisible by any conventional imaging methodologies, clinical examinations of coronary fibrin thrombus have been ignored, and little is known about its role in the genesis of acute coronary syndrome (ACS). The present study was performed to visualize coronary fibrin thrombus and to examine its role in ACS.

Methods And Results: Dye-staining coronary angioscopy using Evans blue dye, which selectively stains fibrin blue but does not stain blood corpuscles, was performed for observation of globular coronary thrombi in 111 ACS patients.

Possible role of damaged neoendothelial cells in the genesis of coronary stent thrombus in chronic phase. A dye staining angioscopic study.

The mechanism(s) underlying formation of coronary stent thrombus (ST) in chronic phase is yet unclear. Endothelial cells are highly antithrombotic, therefore, it is conceivable that neoendothelial cells (NECs) covering stent struts are damaged and cause ST. This study was performed to examine the role of damaged NECs covering coronary stent struts in the genesis of occlusive or nonocclusive ST in chronic phase.

Relationship between cardioscopic images and histological changes in the left ventricle of patients with idiopathic myocarditis.

Aims: Endomyocardial biopsy is essential for definite diagnosis of idiopathic myocarditis. However, since endomyocardial biopsy is guided by fluoroscopy, whether or not the diseased myocardium is biopsied depends on chance, and this may lead to misdiagnosis. If the endocardial surface represents changes indicative of stages of myocarditis, staging of myocarditis and targeted cardioscope-guided biopsy could be used for accurate histological diagnosis.