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1.
Am J Med Genet A ; 191(1): 37-51, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36189931

ABSTRACT

Vascular Ehlers-Danlos syndrome (vEDS) is a hereditary connective tissue disorder (HCTD) characterized by arterial dissection/aneurysm/rupture, sigmoid colon rupture, or uterine rupture. Diagnosis is confirmed by detecting heterozygous variants in COL3A1. This is the largest Asian case series and the first to apply an amplification-based next-generation sequencing through custom panels of causative genes for HCTDs, including a specific method of evaluating copy number variations. Among 429 patients with suspected HCTDs analyzed, 101 were suspected to have vEDS, and 33 of them (32.4%) were found to have COL3A1 variants. Two patients with a clinical diagnosis of Loeys-Dietz syndrome and/or familial thoracic aortic aneurysm and dissection were also found to have COL3A1 variants. Twenty cases (57.1%) had missense variants leading to glycine (Gly) substitutions in the triple helical domain, one (2.9%) had a missense variant leading to non-Gly substitution in this domain, eight (22.9%) had splice site alterations, three (8.6%) had nonsense variants, two (5.7%) had in-frame deletions, and one (2.9%) had a multi-exon deletion, including two deceased patients analyzed with formalin-fixed and paraffin-embedded samples. This is a clinically useful system to detect a wide spectrum of variants from various types of samples.


Subject(s)
Ehlers-Danlos Syndrome, Type IV , Ehlers-Danlos Syndrome , Pregnancy , Female , Humans , Ehlers-Danlos Syndrome/diagnosis , Ehlers-Danlos Syndrome/genetics , Collagen Type III/genetics , DNA Copy Number Variations , Genetic Testing
2.
J Endovasc Ther ; 30(1): 114-122, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35012389

ABSTRACT

PURPOSE: To evaluate the efficacy of the Active Seal technology employed in the AFX endovascular aortic aneurysm system (AFX), during endovascular aneurysm repair (EVAR) in patients with abdominal aortic aneurysms (AAAs) having a conical proximal neck. MATERIALS AND METHODS: A retrospective analysis of the EVAR for AAA with a conical proximal neck using the AFX was performed at 17 Japanese hospitals between January 2016 and August 2020. The conical proximal neck was defined as a cone-shaped proximal neck, with more than 10% diameter increase within a 15 mm length at the proximal landing zone. All anatomical analyses were performed in the core laboratory, and cases with parallel walls within the proximal neck adequate for the landing zone were excluded from the study. RESULTS: This study included 53 patients, but only 39 patients (mean age, 76.6 ± 6.7 years; 87.0% males; mean aneurysm diameter, 52.0 ± 8.0 mm) were analyzed after being characterized as having a pure conical neck by the core laboratory. The mean proximal neck diameters at the lower renal artery and proximal edge of the aneurysm were 20.0 ± 2.9 mm and 27.5 ± 4.9 mm, respectively. The mean proximal neck length was 21.5 ± 6.0 mm. Instructions for use violations other than the conical neck were observed in 15 patients (38.5%). The VELA cuff was used in all cases; however, additional proximal cuff was required in 9 more cases (23.1%). The Active Seal technology was able to significantly extend the proximal sealing zone from 21.5 ± 6.0 to 26.0 ± 12.2 mm (p = .047). Thirty-six patients completed the 12-month follow-up (one patient was lost to follow-up, and 2 patients died from causes unrelated to the aneurysm), and there were no type-1a and 3 endoleaks with only one reintervention (2.6%) related to type 1b endoleak in the 12-month period. Furthermore, there was no significant enlargement of the proximal neck diameter at 12 months (at 1 month: 20.6 ± 3.4 mm and at 12 months: 21.3 ± 3.8 mm; p = .420). CONCLUSION: The Active Seal technology of the AFX significantly extended the proximal seal zone and no type-1a endoleak and proximal neck dilation was observed in patients with conical proximal neck at 12 months.


Subject(s)
Aortic Aneurysm, Abdominal , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Male , Humans , Aged , Aged, 80 and over , Female , Blood Vessel Prosthesis/adverse effects , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/surgery , Aortic Aneurysm, Abdominal/complications , Blood Vessel Prosthesis Implantation/adverse effects , Stents/adverse effects , Endoleak/diagnostic imaging , Endoleak/etiology , Endoleak/therapy , Retrospective Studies , Treatment Outcome , Prosthesis Design , Endovascular Procedures/adverse effects , Risk Factors
3.
J Endovasc Ther ; : 15266028221109477, 2022 Jul 11.
Article in English | MEDLINE | ID: mdl-35815459

ABSTRACT

PURPOSE: To evaluate the clinical utility of the Gore Excluder iliac branch endoprosthesis (IBE) for Japanese patients with aortoiliac aneurysms. MATERIALS AND METHODS: This was a multicenter retrospective cohort study (J-Preserve Registry). Patients undergoing endovascular aortic repair using the Gore Excluder IBE for aortoiliac aneurysms between August 2017 and June 2020 were enrolled. Data pertaining to the baseline and anatomical characteristics, technical details, and clinical outcomes were collected from each institution. The primary endpoints were technical success, IBE-related complications, and reinterventions. Secondary endpoints were mortality, aneurysm size change, and reintervention during follow-up. Technical success was defined as accurate deployment of the IBE without type Ib, Ic, or III endoleaks on the IBE sides on completion angiography. A change in aneurysm size of 5 mm or more was taken to be a significant change. RESULTS: We included 141 patients with 151 IBE implantations. Sixty-five IBE implantations (43.0%) had at least one instruction for use violation. Twenty-two patients (15.6%) required internal iliac artery (IIA) embolization for external iliac artery extension on the contralateral side. Of 151 IBE implantations, 19 exhibited IIA branch landing zones due to IIA aneurysms. Mean maximum and proximal common iliac artery (CIA) diameters were 32.9±9.9 mm and 20.5±6.9 mm, respectively. The mean CIA length was 59.1±17.1 mm. The IIA landing diameter and length were 9.0±2.3 mm and 33.8±14.6 mm. The overall technical success rate was 96.7%. There were no significant differences in IBE-related complications (2.3% vs 5.3%, p=0.86) or IBE-related reinterventions (1.5% vs 5.3%, p=0.33) between the IIA trunk and IIA branch landing groups. The mean follow-up period was 635±341 days. The all-cause mortality rate was 5.0%. There were no aneurysm-related deaths or ruptures during the follow-up. Most patients (95.7%) had sac stability or shrinkage. CONCLUSION: The Gore Excluder IBE was safe and effective for Japanese patients in the midterm. Extending the IIA device into the distal branches of the IIA was acceptable, which may permit extending indications for endovascular aortic aneurysm repair of aortoiliac aneurysms to more complex lesions. CLINICAL IMPACT: This study suggests clinical benefits of the Gore Excluder IBE for Japanese patients, despite 43% of the IBE implantations having at least one IFU violation.

4.
J Vasc Surg ; 67(2): 490-497, 2018 02.
Article in English | MEDLINE | ID: mdl-28943006

ABSTRACT

OBJECTIVE: We developed a mini-incision eversion carotid endarterectomy (CEA) procedure (the Jikei method CEA) to prevent perioperative embolic stroke. The aim of this study was to retrospectively analyze perioperative and midterm outcomes after the Jikei method CEA. METHODS: We evaluated patients with the Jikei method CEA at our institution between January 2006 and June 2014. The primary end point was a major adverse event, which included death, stroke, intracranial hemorrhage, and myocardial infarction, within 30 days of CEA. Secondary end points were postoperative ipsilateral stroke and restenosis. RESULTS: We retrospectively studied 120 lesions in 110 patients. The mean age was 72.2 ± 8.0 years. With regard to the 120 lesions, 56 lesions (46.7%) were symptomatic and 73 lesions (60.8%) showed ≥90% severe stenosis. The mean length of the skin incision was 3.2 ± 0.5 cm. The mean operative time, volume of blood loss, and internal carotid artery clamp time were 171.0 ± 50.7 minutes, 161.6 ± 110.8 mL, and 35.7 ± 10.8 minutes, respectively. There were three perioperative major adverse events (2.5%), including two strokes (1.7%) and one intracranial hemorrhage (0.8%) resulting from hyperperfusion syndrome. The median postoperative hospital stay was 6 days (range, 2-303 days). The mean follow-up was 3.9 ± 2.2 years. There was no case of ipsilateral stroke during the follow-up period. The freedom from ipsilateral stroke at 5 years was 98.3%. Three lesions (2.5%) developed restenosis. The freedom from restenosis was 97.2% at 5 years. The freedom from reintervention at 5 years was 99.0% because carotid artery stent placement was necessary in one patient with severe restenosis. CONCLUSIONS: The Jikei method CEA was safe and effective in preventing perioperative and midterm stroke.


Subject(s)
Carotid Artery, Internal/surgery , Carotid Stenosis/surgery , Endarterectomy, Carotid/methods , Aged , Aged, 80 and over , Angiography , Carotid Artery, Internal/diagnostic imaging , Carotid Stenosis/complications , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/mortality , Disease-Free Survival , Endarterectomy, Carotid/adverse effects , Endarterectomy, Carotid/mortality , Female , Humans , Intracranial Embolism/etiology , Intracranial Embolism/prevention & control , Intracranial Hemorrhages/etiology , Kaplan-Meier Estimate , Length of Stay , Male , Middle Aged , Recurrence , Retrospective Studies , Risk Factors , Stroke/etiology , Stroke/prevention & control , Time Factors , Tokyo , Treatment Outcome
5.
Kyobu Geka ; 69(13): 1102-1105, 2016 Dec.
Article in Japanese | MEDLINE | ID: mdl-27909280

ABSTRACT

We report a rare case of cardiac failure for intrapericardial hematoma 11 years after coronary artery bypass grafting. A 59-year-old man was admitted to our hospital with cardiac tamponade. Echocardiography and computed tomography scan showed severe compression of the left ventricle(LV) by a large mass sized about 5×8 cm. Coronary angiography showed total occlusion at circumflex branch (Cx) #11. The mass was diagnosed with intrapericardial hematoma. We performed removal of hematoma in the pericardial cavity, and removed hematoma had 126 g. Considering that the patient had suffered from diabetes mellitus, the localized collection of the hematoma might be explained by possible slow oozing from LV free wall rupture after asymptomatic myocardial infarction at Cx area.


Subject(s)
Cardiac Tamponade/surgery , Coronary Artery Bypass/adverse effects , Heart Failure/surgery , Cardiac Tamponade/diagnostic imaging , Cardiac Tamponade/etiology , Heart Failure/diagnostic imaging , Heart Failure/etiology , Humans , Male , Middle Aged , Tomography, X-Ray Computed , Treatment Outcome
6.
J Endovasc Ther ; 22(4): 640-6, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26092539

ABSTRACT

PURPOSE: To clarify the current status of surgical site infection (SSI) during endovascular aortic repair and to define risk factors for SSI among the patients who underwent thoracic or abdominal stent-graft repair through a groin incision. METHODS: Between 2006 and 2013, data were collected from 1604 patients (mean age 75.2±9.5 years; 1282 men) with 2799 groin incisions for transfemoral access during aortic stent-graft procedures. SSIs were classified as superficial or deep (both occurring within 30 days) or organ/space infections (occurring within 1 year after surgery) according to the Centers for Disease Control and Prevention guidelines. Strategies in place for minimizing SSIs were (1) employing oblique groin incisions, (2) covering the incision with saline-soaked gauze, (3) irrigating the incision thoroughly with saline per layer, and (4) using absorbable sutures. RESULTS: Overall incidence of SSI was 0.4% (6 patients). The majority of SSIs were late-onset prosthetic graft infections (5, 0.3%). Five of the 6 were successfully treated with conservative therapy; one patient died of sepsis. Univariate analysis showed additional therapy (eg, coil embolization) with a stent-graft procedure was a risk factor for SSI. CONCLUSION: Appropriate antibiotic administration, oblique groin incision, meticulous operative technique, protection against airborne infection during the operation, and closed dressings may avert vascular wound SSIs.


Subject(s)
Aortic Aneurysm/surgery , Blood Vessel Prosthesis , Endovascular Procedures , Surgical Wound Infection/prevention & control , Vascular Surgical Procedures , Aged , Female , Groin/surgery , Humans , Male , Risk Factors , Stents , Treatment Outcome
7.
Asian J Endosc Surg ; 16(3): 533-536, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36599190

ABSTRACT

Injury to the right gastroepiploic artery (RGEA) graft during gastrectomy after coronary artery bypass grafting (CABG) can cause critical coronary failure. A man in his 60s with advanced gastric cancer and a history of CABG was admitted to our hospital. His cardiac blood flow was dependent on RGEA, and a gastrectomy with RGEA preservation was necessary. Robot-assisted distal gastrectomy with real-time vessel navigation using indocyanine green (ICG) fluorescence imaging and Da Vinci Firefly technology was planned. Intraperitoneal observation revealed severe adhesions around the graft. Two milliliters ICG (2.5 mg/mL) was injected intravenously, and RGEA was visualized. An RGEA-preserving robot-assisted distal gastrectomy was successfully performed. The operation time was 279 minutes, and the blood loss was 5 mL. The postoperative course was good and there were no complications.


Subject(s)
Gastroepiploic Artery , Robotic Surgical Procedures , Stomach Neoplasms , Male , Humans , Stomach Neoplasms/surgery , Stomach Neoplasms/complications , Indocyanine Green , Gastroepiploic Artery/transplantation , Fluorescence , Coronary Artery Bypass/methods , Gastrectomy/methods
8.
Surg Case Rep ; 8(1): 65, 2022 Apr 13.
Article in English | MEDLINE | ID: mdl-35416607

ABSTRACT

BACKGROUND: Acute arterial embolization caused by a free-floating thrombus of the false lumen after surgery for acute aortic dissection is a rare complication; hence, determining its cause may be difficult. We report a case in which angioscopy was valuable in diagnosing and treating the unstable thrombus within the false lumen. CASE PRESENTATION: The patient was a 71-year-old woman who underwent hemiarch replacement for Stanford type A acute aortic dissection. Two months after the operation, left renal infarction occurred. Eighteen months after the operation, the patient visited the hospital for treatment of intermittent claudication of her left leg. Computed tomography (CT) showed occlusion below the left common femoral artery. Surgical thrombectomy was performed for acute lower extremity arterial occlusion. One month later, thrombectomy was performed again for the same phenomenon and again after 2 months. She had no history of cardiac arrhythmia. No obvious source for the repeat embolization could be found on echocardiography or enhanced CT. Angiography was performed to further identify the cause, revealing a new entry site at the distal anastomosis, which exhibited antegrade flow into the false lumen. Furthermore, selective false lumen angiography via the re-entry revealed a thrombus in the false lumen corresponding to the descending aorta. A non-obstructive angioscopy system in the false lumen revealed a free-floating thrombus. As the patient had undergone multiple surgeries over a short period and desired minimally invasive treatment, coil embolization of the new entry site as well as false lumen was performed. As a result, blood flow from the true to the false lumen resolved. More than 1 year has passed following coil embolization with no signs of embolism. CONCLUSIONS: We experienced a case of repeat embolism caused by unstable thrombus formation in the false lumen resulting from antegrade blood flow in the false lumen secondary to development of a new entry site. Angioscopy revealed that this antegrade flow caused formation of an unstable thrombus which caused recurrent acute lower extremity arterial occlusion. Therefore, angioscopy may be a useful option for the diagnosis of false lumen thrombosis.

9.
Eur J Cardiothorac Surg ; 62(2)2022 07 11.
Article in English | MEDLINE | ID: mdl-35876861

ABSTRACT

OBJECTIVES: Our goal was to analyse the relationships between aortic surface irregularity and a type 1 endoleak (T1EL) after a thoracic endovascular repair using the Najuta fenestrated stent graft. METHODS: The patients who were treated using the Najuta stent graft for an intact aortic arch aneurysm at the Saitama Cardiovascular and Respiratory Center between June 2013 and June 2017 were analysed retrospectively. The primary end point was the occurrence of a T1EL. The gap between a virtual aorta and the patient's aortic wall at the stent graft fixation was calculated over the whole circumference at 1 mm intervals, and gap distribution mapping was performed. The rate of freedom from a T1EL was estimated using the Kaplan-Meier method and compared between the patients with or without a continuously malapposed region of >1 mm from the branches to the aneurysm. RESULTS: Twenty-one patients were analysed. During the mean follow-up period of 21.7 months, 4 patients were confirmed to have T1ELs. Three of the T1Els were detected during the perioperative period and occurred through a fenestration. The remaining patient had a T1EL 2 years postoperatively. The gap distribution mapping confirmed the presence of a continuously malapposed region of >1 mm from the cervical branch to the aneurysm postoperatively in 4 patients with T1ELs. Patients who had a continuously malapposed region of >1 mm showed a statistically lower T1EL rate than those without (p < 0.001). Malapposed regions defined using the gap distribution mapping were consistent with flow channels through T1EL fenestrations detected using the perioperative computed tomography data. CONCLUSIONS: The gap distribution mapping could be useful to predict the occurrence of T1ELs in patients with the Najuta stent graft.


Subject(s)
Aortic Aneurysm, Thoracic , Aortic Dissection , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Aortic Dissection/surgery , Aortic Aneurysm, Thoracic/etiology , Aortic Aneurysm, Thoracic/surgery , Blood Vessel Prosthesis/adverse effects , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/methods , Endoleak/etiology , Endoleak/surgery , Endovascular Procedures/adverse effects , Endovascular Procedures/methods , Humans , Prosthesis Design , Retrospective Studies , Stents/adverse effects , Treatment Outcome
10.
Kyobu Geka ; 64(1): 32-8, 2011 Jan.
Article in Japanese | MEDLINE | ID: mdl-21229676

ABSTRACT

Thoracic endovascular aneurysm repair (TEVAR) has gained wide acceptance because of its minimal invasiveness and effectiveness for thoracic aortic aneurysms. However, the endovascular technique alone is often not applicable to arch aneurysms due to their anatomical complexity, such as aortic curve and presense of neck branches. The development of branched stent graft that allows total endovascular approach has been slow. Therefore open surgical technique is still needed to obtain an adequate landing zone. Prior total arch replacement with elephant trunk and debranching neck vessels including partial debranching such as carotid-carotid crossover bypass, and total debranching from the ascending aorta were able to create a suitable proximal landing zone. Chimney technique using covered stent for the neck vessels is also effective for arch aneurysms. Here, we report the strategies of TEVAR for aortic arch aneurysms.


Subject(s)
Aortic Aneurysm, Thoracic/therapy , Blood Vessel Prosthesis , Stents , Vascular Grafting/methods , Aortic Aneurysm, Thoracic/surgery , Blood Vessel Prosthesis Implantation/methods , Humans
11.
Nihon Geka Gakkai Zasshi ; 112(6): 394-8, 2011 Nov.
Article in Japanese | MEDLINE | ID: mdl-22165715

ABSTRACT

Carotid endarterectomy (CEA) remains the gold standard for the treatment of carotid artery stenosis even after the approval of carotid artery stenting in Japan. At Jikei University, we have developed a mini incisional eversion CEA that has distinct advantages compared with conventional CEA. First, cerebral infarction has not occurred after this procedure in 70 patients, and therefore the risk of cerebral infarction appears to be lower than after conventional CEA. This is because the internal carotid artery (ICA) is dissected only after clamping of the common and external carotid arteries, thereby arresting the prograde flow that carries emboli to the brain. Second, the duration of ICA clamping is shorter because the anastomosis can be performed in an end-to-side manner without delicate closure, with or without patching. Finally, this eversion CEA requires only a 3-cm incision as compared with conventional CEA that usually requires an approximately 10-cm incision. This Jikei method is extremely minimally invasive with negligible embolic complications, and therefore we believe that this method should become the first-line treatment for most patients with carotid artery stenosis.


Subject(s)
Endarterectomy, Carotid/methods , Intracranial Embolism/prevention & control , Carotid Stenosis/surgery , Cerebral Infarction/prevention & control , Humans
12.
J Vasc Surg ; 51(1): 155-64, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19954921

ABSTRACT

OBJECTIVE: There is an increasing need for vascular grafts in the field of surgical revascularization. However, smaller vascular grafts made from synthetic biomaterials, particularly those <5 mm in diameter, are associated with a high incidence of thrombosis. Fibroin is a biodegradable protein derived from silk. Silk fibroin from Bombyx mori provides an antithrombotic surface and serves as a scaffold for various cell types in tissue engineering. We evaluated the potential of fibroin to generate a vascular prosthesis for small arteries. METHODS: A small vessel with three layers was woven from silk fibroin thread. These fibroin-based grafts (1.5 mm diameter, 10 mm length) were implanted into the abdominal aorta of 10- to 14-week-old male Sprague-Dawley rats by end-to-end anastomosis. Polytetrafluoroethylene (PTFE)-based grafts were used as the control. To investigate the origin of the cells in the neointima and media, bone marrow transplantation was performed from green fluorescent protein (GFP) rats to wild-type rats. RESULTS: The patency of fibroin grafts at 1 year after implantation was significantly higher than that of PTFE grafts (85.1% vs 30%, P < .01). Endothelial cells and smooth muscle cells (SMCs) migrated into the fibroin graft early after implantation and became organized into endothelial and medial layers, as determined by anti-CD31 and anti-alpha-smooth muscle actin immunostaining. The total number of SMCs increased 1.6-fold from 1 month to 3 months. Vasa vasorum also formed in the adventitia. Sirius red staining of the fibroin grafts revealed that the content of collagen significantly increased at 1 year after implantation, with a decrease in fibroin content. GFP-positive cells contributed to organization of a smooth muscle layer. CONCLUSIONS: Small-diameter fibroin-based vascular grafts have excellent long-term patency. Bone marrow-derived cells contribute to vascular remodeling after graft implantation. Fibroin might be a promising material to engineer vascular prostheses for small arteries.


Subject(s)
Absorbable Implants , Aorta, Abdominal/surgery , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis , Fibroins , Vascular Patency , Actins/metabolism , Animals , Aorta, Abdominal/diagnostic imaging , Aorta, Abdominal/metabolism , Aortography , Bone Marrow Cells/metabolism , Bone Marrow Transplantation , Cell Movement , Collagen/metabolism , Endothelial Cells/metabolism , Green Fluorescent Proteins/genetics , Male , Materials Testing , Models, Animal , Myocytes, Smooth Muscle/metabolism , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Polytetrafluoroethylene , Prosthesis Design , Rats , Rats, Sprague-Dawley , Rats, Transgenic , Time Factors , Ultrasonography, Doppler, Color
13.
Arterioscler Thromb Vasc Biol ; 27(4): 813-8, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17272742

ABSTRACT

BACKGROUND: Plasma high-density lipoprotein (HDL) levels have an inverse correlation with incidence of ischemic heart disease as well as other atherosclerosis-related ischemic conditions. However, the molecular mechanism by which HDL prevents ischemic disease is not fully understood. Here, we investigated the effect of HDL on differentiation of endothelial progenitor cells and angiogenesis in murine ischemic hindlimb model. METHODS AND RESULTS: Intravenous injection of reconstituted HDL (rHDL) significantly augmented blood flow recovery and increased capillary density in the ischemic leg. rHDL increased the number of bone marrow-derived cells incorporated into the newly formed capillaries in ischemic muscle. rHDL induced phosphorylation of Akt in human peripheral mononuclear cells. rHDL (50 to 100 microg apolipoprotein A-I/mL) promoted differentiation of peripheral mononuclear cells to endothelial progenitor cells in a dose-dependent manner. The effect of rHDL on endothelial progenitor cells differentiation was abrogated by coadministration of LY294002, an inhibitor of phosphatidylinositol 3-kinase. rHDL failed to promote angiogenesis in endothelial NO-deficient mice. CONCLUSIONS: rHDL directly stimulates endothelial progenitor cell differentiation via phosphatidylinositol 3-kinase/Akt pathway and enhances ischemia-induced angiogenesis. rHDL may be useful in the treatment of patients with ischemic cardiovascular diseases.


Subject(s)
Endothelial Cells/pathology , Hindlimb/blood supply , Ischemia/physiopathology , Lipoproteins, HDL/pharmacology , Neovascularization, Physiologic/drug effects , Stem Cells/pathology , Animals , Bone Marrow/pathology , Cell Differentiation/drug effects , Cells, Cultured , Chimera , Collateral Circulation/drug effects , Humans , Male , Mice , Mice, Inbred Strains , Mice, Knockout , Nitric Oxide Synthase Type III/deficiency , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Regional Blood Flow/drug effects , Signal Transduction
14.
Biomed Pharmacother ; 62(1): 46-52, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17692499

ABSTRACT

Angiogenesis, the formation of new blood vessels, is a physiological response to tissue ischemia. Clinical evidence suggests that diabetic patients have endothelial dysfunction and impaired angiogenesis in response to ischemia. Here, we investigated the impact of diabetes on ischemia-induced collateral growth, and tested the hypothesis that peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist augments collateral flow to ischemic tissue. We conducted unilateral hindlimb ischemia surgery in KKAy mice. Blood flow recovery was markedly impaired in diabetic mice compared with that in wild-type mice as determined by laser Doppler imaging. Treatment of KKAy mice with pioglitazone partially restored the blood flow recovery. Anti-CD31 immunostaining revealed that pioglitazone also significantly improved the capillary density in ischemic limb muscle. Endothelial NO synthase (eNOS) activity was ameliorated in diabetic mice treated with pioglitazone as determined by vasorelaxation in response to acetylcholine. Pioglitazone normalized vascular endothelial growth factor (VEGF) protein levels, which was decreased in ischemic muscle of KKAy mice, and up-regulated eNOS phosphorylation at Ser-1177 and Akt phosphorylation at Ser-473 in ischemic muscle. Pioglitazone had no beneficial effects on blood flow recovery in diabetic mice treated with N(G)-nitro-l-arginine methyl ester (L-NAME). Our findings demonstrate that pioglitazone significantly ameliorates endothelial dysfunction and enhances blood flow recovery after tissue ischemia in diabetic mice. Activation of eNOS appears to be essential for pioglitazone to promote angiogenesis in ischemic tissue.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/pharmacology , Ischemia/physiopathology , Neovascularization, Physiologic/drug effects , Thiazolidinediones/pharmacology , Animals , Diabetes Mellitus, Type 2/physiopathology , Disease Models, Animal , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiopathology , Laser-Doppler Flowmetry , Male , Mice , Mice, Inbred C57BL , Nitric Oxide Synthase Type III/drug effects , Nitric Oxide Synthase Type III/metabolism , PPAR gamma/agonists , Phosphorylation , Pioglitazone , Up-Regulation/drug effects
16.
Life Sci ; 80(6): 559-65, 2007 Jan 16.
Article in English | MEDLINE | ID: mdl-17157325

ABSTRACT

Therapeutic angiogenesis has emerged as a promising therapy to treat patients with ischemic diseases. Transplantation of bone marrow cells (BMCs) is reported to augment collateral development in ischemic organs either by differentiating into vascular cells or by secreting angiogenic cytokines. Recent evidence suggests that adipose tissues secrete a number of humoral factors and contain pluripotent stem cells. Here, we evaluated the therapeutic potential of adipose tissue-derived cells to promote angiogenesis in a mouse model of hind limb ischemia. Stromal vascular fraction cells (SVFs) were isolated from inguinal adipose tissue. Endothelial-like cells or smooth muscle-like cells could be obtained from the culture of SVFs in the presence of growth factors. Freshly isolated BMCs, SVFs, or mature adipocytes were transplanted into the ischemic hind limb of mice. SVFs significantly augmented collateral development as determined by the restoration of blood perfusion and capillary density of the ischemic muscle. Angiogenic effects of SVFs were as potent as those of BMCs. Mature adipocytes showed no proangiogenic effects. The ischemic muscle contained endothelial cells or smooth muscle cells that derived from the transplanted SVFs and BMCs. These results suggest that SVFs might be used to promote angiogenesis in ischemic tissues.


Subject(s)
Adipocytes/transplantation , Adipose Tissue/cytology , Ischemia/therapy , Lower Extremity/blood supply , Neovascularization, Physiologic , Stromal Cells/transplantation , Animals , Cell Differentiation , Green Fluorescent Proteins/genetics , Ischemia/physiopathology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Regional Blood Flow
17.
Biomed Pharmacother ; 61(4): 209-15, 2007 May.
Article in English | MEDLINE | ID: mdl-17223008

ABSTRACT

OPC-28326, 4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl) piperidine hydrochloride monohydrate, is a newly developed selective peripheral vasodilator and increases blood flow to lower extremities with alpha2-adrenergic antagonist property. Here, we investigated the effect of OPC-28326 on ischemia-induced angiogenesis. OPC-28326 enhanced tube formation by human aortic endothelial cells (HAECs). Moreover, OPC-28326 enhanced the number of microvessels sprouting from aortic rings embedded in collagen gel. OPC-28326 markedly induced phosphorylation of endothelial nitric oxide synthase (eNOS) in HAECs via phosphatidylinositol-3 kinase PI3K/Akt (PI3K/Akt) pathway. Next, the angiogenic effect of OPC-28326 was evaluated in a mouse hindlimb ischemia model. Blood flow recovery to the ischemic leg was significantly enhanced by OPC-28326. Furthermore, anti-CD31 immunostaining revealed that OPC-28326 increased capillary density in the ischemic muscle. However, OPC-28326 failed to promote blood flow recovery in ischemic hindlimb in eNOS-deficient mice. These results suggest that OPC-28326 promotes angiogenesis, which was associated with activation of eNOS via PI3K/Akt pathway. OPC-28326 might be promising to treat patients with ischemic vascular diseases.


Subject(s)
Aniline Compounds/pharmacology , Ischemia/physiopathology , Neovascularization, Physiologic/drug effects , Piperidines/pharmacology , Vasodilator Agents/pharmacology , Animals , Aorta/cytology , Aorta/drug effects , Aorta/physiology , Blotting, Western , Cells, Cultured , Dose-Response Relationship, Drug , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Endothelium, Vascular/cytology , Hindlimb/blood supply , Humans , In Vitro Techniques , Laser-Doppler Flowmetry , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Nitric Oxide Synthase Type III/genetics , Nitric Oxide Synthase Type III/metabolism , Phosphorylation , Rats , Regional Blood Flow
18.
World J Gastroenterol ; 13(5): 692-8, 2007 Feb 07.
Article in English | MEDLINE | ID: mdl-17278191

ABSTRACT

AIM: To investigate the roles of Bax and p53 proteins in photosensitivity of human colon cancer cells by using lysosome-localizing photosensitizer, ATX-S10Na (II). METHODS: HCT116 human colon cancer cells and Bax-null or p53-null isogenic derivatives were irradiated with a diode laser. Early apoptosis and cell death in response to photodynamic therapy were determined by MTT assays, annexin V assays, transmission electron microscopy assays, caspase assays and western blotting. RESULTS: Induction of early apoptosis and cell death was Bax- and p53-dependent. Bax and p53 were required for caspase-dependent apoptosis. The levels of anti-apoptotic Bcl-2 family proteins, Bcl-2 and Bcl-x(L), were decreased in Bax- and p53-independent manner. CONCLUSION: Our results indicate that early apoptosis and cell death of human colon cancer cells induced by photodynamic therapy with lysosome-localizing photosensitizer ATX-S10Na (II) are mediated by p53-Bax network and low levels of Bcl-2 and Bcl-x(L) proteins. Our results might help in formulating new therapeutic approaches in photodynamic therapy.


Subject(s)
Apoptosis/drug effects , Colonic Neoplasms/pathology , Photosensitizing Agents/pharmacology , Porphyrins/pharmacology , Tumor Suppressor Protein p53/genetics , bcl-2-Associated X Protein/genetics , Apoptosis/physiology , HCT116 Cells , Humans , Photochemotherapy , Tumor Suppressor Protein p53/metabolism , bcl-2-Associated X Protein/metabolism
19.
Semin Vasc Surg ; 20(2): 115-20, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17580249

ABSTRACT

The purpose of endovascular aortic aneurysm repair is to depressurize the sac and to protect it from rupture. However, none of the imaging modality currently used during the follow-up period including CTA, MRA and duplex ultrasound can measure sac pressure. Noninvasive sac pressure monitoring using implantable sensors has the potential to provide a safe, reliable, cost-effective alternative for post-EVAR surveillance. The technology is compatible with all types of imaging, all types of implants, and allows clinicians to obtain physiologic data to supplement their assessment of the aneurysm repair. These devices may ultimately allow for measurements to be obtained at home, with an unlimited frequency without risk to the patient, added cost or complexity. We believe that not only is development of an intrasac transducer necessary, but it is a desirable adjunct to endovascular aneurysm repair, and an adjunct that might possibly eliminate some of the complex imaging protocols that are presently necessary over long-term follow-up.


Subject(s)
Aortic Aneurysm/diagnosis , Blood Vessel Prosthesis Implantation , Monitoring, Ambulatory/instrumentation , Postoperative Care/instrumentation , Telemetry/instrumentation , Aortic Aneurysm/physiopathology , Aortic Aneurysm/surgery , Aortography/methods , Electrodes, Implanted , Equipment Design , Humans , Imaging, Three-Dimensional , Magnetic Resonance Angiography , Postoperative Care/methods , Pressure , Radiographic Image Interpretation, Computer-Assisted , Tomography, X-Ray Computed , Transducers, Pressure , Treatment Outcome , Ultrasonography, Doppler, Duplex
20.
Nihon Geka Gakkai Zasshi ; 108(4): 194-8, 2007 Jul.
Article in Japanese | MEDLINE | ID: mdl-17665559

ABSTRACT

Bypass surgery is still considered the "gold standard" therapy for the treatment of critical limb ischemia (CLI). However, due to recent advances in endovascular technologies, catheter-based intervention has become a viable option, and percutaneous treatment is becoming more widely used. This paper provides a brief overview of the percutaneous therapies available today and new technologies on the horizon as well as highlights some advantages and limitations of each treatment option in CLI.


Subject(s)
Ischemia/therapy , Leg/blood supply , Stents , Angioplasty, Balloon , Critical Illness , Humans
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