Detecting intimal tear and subintimal blood flow of thrombosed acute aortic dissection with ulcer-like projections using non-obstructive angioscopy.

A 73-year-old man reporting severe chest and back pain for 20 min was admitted to our hospital. The pain occurred 3 days before admission. Computed tomography angiography showed a hazy-surfaced low-density area in the aortic arch with aneurysmal formation of unknown etiology. It was inconclusive whether the aortic change was acute or chronic because no previous information was available. To investigate the etiology, non-obstructive angioscopy (NOA) was performed. A fissure with blood flow was detected at the surface of the low-density area and active subintimal blood flow was demonstrated on NOA. An entry tear and active blood flow below the intima at the seemingly thrombosed area suggested that the patient had a thrombosing type B aortic dissection. .

Exploring inside a shaggy aorta using non-obstructive angioscopy.

A shaggy aorta is reportedly related to atheromatous embolisation, which causes serious ischaemic damage to various organs. However, its characteristics are poorly understood. Non-obstructive angioscopy (NOA) has been developed to safely detect aortic plaques and injuries. A 70-year-old woman who was found to have a shaggy aorta on CT angiography underwent NOA for precise evaluation of vulnerable aortic plaques and injuries inside the aorta. Vulnerable aortic plaques included puff-like ruptures, chandelier-like ruptures and erosions seen throughout the aorta. Aortic injuries included flaps, slits, subintimal bleeding, dissection and multilayered partitions. The patient had no embolic symptoms or an elevated eosinophil count, estimated glomerular filtration rate or C reactive protein level, compared with the baseline. Various changes in spontaneous vulnerable plaques and injuries inside the aorta that were not apparent on CT were safely revealed on NOA. Thus, NOA may reveal findings indicative of spontaneous and postoperative atheromatous embolisation.

Reduction in morning blood pressure is a key factor for ameliorating urinary albumin excretion in patients with morning hypertension irrespective of treatment regimen.

BACKGROUND: The Morning Hypertension and Angiotensin Receptor Blocker/Hydrochlorothiazide Combination Therapy (MAPPY) study has shown that losartan/hydrochlorothiazide (HCTZ) combination is superior to high-dose losartan in not only reducing morning systolic blood pressure (SBP) but also ameliorating urinary albumin excretion (UAE) after 3-month treatment. The purpose of the present study was to investigate factors associated with UAE reduction in on-treatment patients with morning hypertension. METHODS AND RESULTS: A total of 95 patients registered in the MAPPY study were analyzed. Patients were treated with either a losartan/HCTZ combination regimen (n=47) or a high-dose losartan regimen (n=48). Three-month treatment significantly reduced morning SBP, evening SBP, and clinic SBP (P<0.001, P<0.05, and P<0.01, respectively). UAE and serum uric acid were significantly decreased (P<0.01 for both) without the change in estimated glomerular filtration rate. Multiple linear regression analysis indicated that %morning SBP reduction and baseline UAE were independent determinants of the UAE reduction (P=0.001 for both). After adjustments for the reduction in morning-evening SBP difference, baseline UAE, and %uric acid reduction, estimated %UAE reduction level was positively correlated with the tertiles of the increasing %morning SBP reduction level (P=0.031 for trend). Moreover, subgroup analysis showed that morning SBP reduction was an independent determinant of UAE reduction in both treatment regimens. CONCLUSIONS: Reduction in morning SBP was a key factor in UAE reduction in patients with morning hypertension, irrespective of treatment regimen.

Platelet-derived microparticles augment the adhesion and neovascularization capacities of circulating angiogenic cells obtained from atherosclerotic patients.

OBJECTIVE: The neovascularization-related capacities of circulating angiogenic cells (CACs) are impaired in atherosclerotic patients, which may explain the unsatisfactory effects of therapeutic angiogenesis with atherosclerotic patient-derived CACs. Platelet-derived microparticles (PMPs) were reported to augment the re-endothelialization capacity of CACs. Accordingly, we investigated whether PMPs could augment the neovascularization-related capacities of atherosclerotic patient-derived CACs in vitro and in vivo and if so, the associated mechanisms. METHODS AND RESULTS: We isolated mononuclear cells and PMPs from atherosclerotic patient-derived peripheral blood and generated PMP-pretreated CACs (PMP-CACs) by co-culture of the mononuclear cells and PMPs. Although the migration capacity of PMP-CACs was similar to that of CACs, the adhesion capacity of PMP-CACs was greater. PMPs released RANTES into the culture medium, and the receptors were similarly expressed on the surfaces of CACs and PMP-CACs. Intravenous injection of PMP-CACs to rats with hindlimb ischemia augmented neovascularization of the ischemic limbs more than the injection of CACs. The number of PMP-CACs incorporated into the capillaries of the ischemic limbs was greater than that of incorporated CACs. The augmented adhesion and neovascularization capacities by PMP-CACs were canceled out by a RANTES neutralizing antibody. CONCLUSIONS: PMP-secreted RANTES may play a role in the augmenting adhesion and neovascularization capacities of CACs. Injection of PMP-CACs may be a new strategy to augment the effects of therapeutic angiogenesis for limb ischemia in atherosclerotic patients.

Coronary endothelial dysfunction distal to stent of first-generation drug-eluting stents.

OBJECTIVES: This study sought to evaluate the relationship between coronary endothelial function and neointimal coverage after drug-eluting stent (DES) implantation. BACKGROUND: The mechanisms of endothelial dysfunction after DES implantation remain to be fully elucidated. We hypothesized that poor neointimal coverage after DES implantation may be associated with endothelial dysfunction distal to the stent site. METHODS: Sixty-six stable angina patients treated with a first-generation DES were enrolled. At 9-month follow-up, coronary endothelial function was evaluated with intracoronary infusion of incremental doses of acetylcholine (10(-8), 10(-7), and 10(-6) mol/l) and nitroglycerin (200 µg). Vascular responses at the segments proximal and distal to the stent site were angiographically and quantitatively measured. At the same time, the degree of neointimal coverage was evaluated using coronary angioscopy and classified into 4 grades: 0 (no coverage) to 3 (full coverage). RESULTS: We divided the subjects into poor-coverage (grades 0 to 1, n = 33) and good-coverage (grades 2 to 3, n = 33) groups. Acetylcholine induced dose-dependent coronary vasoconstrictions in both groups. At the segment distal to the stent, the magnitude of vasoconstriction to acetylcholine in the poor-coverage group was significantly greater than in the good-coverage group (p < 0.001), whereas vasomotor responses proximal to the stent and vasodilation by nitroglycerine were similar between the 2 groups. CONCLUSIONS: Coronary endothelial dysfunction distal to the stent was associated with poor neointimal coverage after DES implantation.

Ultrasound stimulation restores impaired neovascularization-related capacities of human circulating angiogenic cells.

AIMS: Unsatisfactory effects of therapeutic angiogenesis in critical limb ischaemia may be ascribed to use of circulating angiogenic cells (CACs) derived from atherosclerotic patients with impaired neovascularization-related capacities. We tested whether ultrasound cell stimulation can restore the impaired capacities. METHODS AND RESULTS: During culture of human peripheral blood-derived mononuclear cells for 4 days to achieve CACs, we stimulated the cells in culture daily with low-intensity pulsed ultrasound stimulation (LIPUS). Application of LIPUS to cells in culture derived from healthy volunteers augmented the generation and migration capacities of CACs, increased concentrations of angiopoietin 2 and nitrogen oxides in the culture medium, and increased the expression of phosphorylated-Akt and endothelial nitric oxide synthase in CACs on western blotting. Application of LIPUS to cells in culture derived from atherosclerotic patients also augmented the generation and migration capacities of CACs. Although neovascularization in the ischaemic hindlimb of athymic nude mice was impaired after intramuscular injection of CACs derived from atherosclerotic patients compared with that using CACs derived from healthy volunteers, LIPUS of the cells in culture derived from atherosclerotic patients restored the neovascularization capacities. CONCLUSION: Therapeutic angiogenesis with LIPUS-pre-treated CACs may be a new strategy to rescue critical limb ischaemia in atherosclerotic patients.

Augmented neovascularization with magnetized endothelial progenitor cells in rats with hind-limb ischemia.

Augmenting neovascularization with the use of endothelial progenitor cells (EPCs) is a therapeutic option to rescue critical limb ischemia (CLI). However, the outcomes have been not so satisfactory. The detectable number of injected EPCs at the ischemic site is rather small. If EPCs accumulate more and stay longer there, neovascularization will be augmented. In this study, we tested whether external magnetic forces (EMFs) accumulated magnetized EPCs (Mag-EPCs) at the ischemic site and thereby augmented neovascularization. We cultured peripheral blood-derived mononuclear cells to obtain EPCs and generated Mag-EPCs by a magnetofection method with nanoparticles. Prussian-blue staining revealed magnetic nanoparticles incorporated into the cytoplasms and nuclei of Mag-EPCs. The survival rate of Mag-EPCs at day 9 of culture was 98.7%, indicating no cell toxicity of magnetic nanoparticles. EMFs augmented adhesion capacity of Mag-EPCs not only in the static but also in the flow condition in vitro, compared to without EMFs. The migration capacity of Mag-EPCs with EMFs was 160% more than EPCs or Mag-EPCs without them. After an intravenous injection of Mag-EPCs into the rat with hind-limb ischemia, the recovery of blood flow and capillary density in the ischemic limb were significantly more (p<0.01) with EMFs than without them. EMFs augmented neovascularization capacity of Mag-EPCs compared to EPCs alone. This method could be a new therapeutic strategy for patients with CLI.

Early outgrowth EPCs generation is reduced in patients with Buerger's disease.

BACKGROUND: Buerger's disease often shows poor collateral artery generation (i.e. neovascularization) in the ischemic limbs. However, the etiology has not yet been clarified. Circulating endothelial progenitor cells (EPCs) derived from bone marrow contribute to neovascularization in the multi-step process which includes the following capacities; mobilization, differentiation, adhesion, migration, invasion and secretion. MATERIALS AND METHODS: We assessed EPCs capacities in vitro and ex vivo in age- and sex-matched controls (n = 12) and patients with Buerger's disease (n = 12), derived from peripheral blood-derived mononuclear cells (PB-MNCs). RESULTS: In the flow cytometry analysis, the numbers of circulating EPC (CD34(+)/KDR(+) or CD133(+)/KDR(+) PB-MNC) were similar between controls and patients with Buerger's disease. Next, we cultured PB-MNC to obtain EPCs. The number of early outgrowth EPCs was significantly decreased in patients with Buerger's disease (p < 0.005), indicating the reduced generation of early outgrowth EPCs in Buerger's disease. However, adhesion, migration, invasion and secretion capacities were not impaired in patients with Buerger's disease. CONCLUSIONS: The early outgrowth EPCs generation is reduced in patients with Buerger's disease.