Use of an On-X Prosthetic Valve In A 42-Year Old Female With Antiphospholipid Syndrome.

Antiphospholipid syndrome is a rare autoimmune disease with a hypercoagulable state causing vascular thrombosis. We present the case of a 42-year old female who underwent mitral valve replacement with a mechanical valve 15 months ago. The postoperative course was uneventful, and echocardiography performed 14 months postoperatively showed good valve function. The patient developed sudden dyspnea 15 months postoperatively and was referred to our hospital. Echocardiography revealed mitral stenosis with stuck leaflets. Emergent re-mitral valve replacement was successfully performed using an On-X valve (On-X Life Technologies, Austin, TX, USA). The patient tested positive for antiphospholipid antibodies. Antiphospholipid syndrome should be considered when valve dysfunction occurs suddenly in relatively young female patients. The On-X valve may be considered as a therapeutic option in patients with antiphospholipid syndrome because of its low anticoagulation intensity.

[Concurrent Mitral and Tricuspid Valve Surgery in a Patient with Left Collapsed Lung;Report of a Case].

A 77-year-old man was referred to our hospital with severe mitral valve regurgitation. Secondary to left partial lobectomy for tuberculosis 55 years earlier, his mediastinum was shifted to the left, and his pulmonary function was moderately decreased. Mitral valve replacement and tricuspid annuloplasty were performed with a median sternotomy. Although the heart was shifted to the left, the mitral valve was easily visualized when the right side of the pericardium was extensively elevated. The tracheal intubation tube was removed 1 day after the operation. The patient's postoperative course was uneventful, and he was discharged on the 13th postoperative day. We describe our surgical strategy in this patient with a literature review.

[Redo Aortic and Mitral Valve Replacement by Manouguian's Procedure for Active Prosthetic Valve Infection].

The damage to the intervalvular fibrous trigone (IVFT) by infective endocarditis makes combined aortic and mitral valve replacement difficult. We performed Manouguian's double valve replacement for such a case and obtained a good result. A 81-year-old male underwent emergency operation due to active prosthetic valve endocarditis. He had a history of receiving combined aortic and mitral valve replacement because of active infective endocarditis at the age of 74 and redo aortic valve replacement 3 years after that. The infectious lesion extended from the mitral annulus to the IVFT and the aortic annulus, and it caused the prosthetic valve detachment from the aortic annulus. Manouguian's double valve replacement was required for radical resection and reconstruction of the IVFT. No recurrent infection or paravalvular leakage was observed during 49months follow up period. Manouguian's procedure is useful for complete resection of the infected IVFT and makes combined aortic and mitral valve replacement safer.

Role of endothelial cell-derived angptl2 in vascular inflammation leading to endothelial dysfunction and atherosclerosis progression.

OBJECTIVE: Cardiovascular disease (CVD), the most common morbidity resulting from atherosclerosis, remains a frequent cause of death. Efforts to develop effective therapeutic strategies have focused on vascular inflammation as a critical pathology driving atherosclerosis progression. Nonetheless, molecular mechanisms underlying this activity remain unclear. Here, we ask whether angiopoietin-like protein 2 (Angptl2), a proinflammatory protein, contributes to vascular inflammation that promotes atherosclerosis progression. APPROACH AND RESULTS: Histological analysis revealed abundant Angptl2 expression in endothelial cells and macrophages infiltrating atheromatous plaques in patients with cardiovascular disease. Angptl2 knockout in apolipoprotein E-deficient mice (ApoE(-/-)/Angptl2(-/-)) attenuated atherosclerosis progression by decreasing the number of macrophages infiltrating atheromatous plaques, reducing vascular inflammation. Bone marrow transplantation experiments showed that Angptl2 deficiency in endothelial cells attenuated atherosclerosis development. Conversely, ApoE(-/-) mice crossed with transgenic mice expressing Angptl2 driven by the Tie2 promoter (ApoE(-/-)/Tie2-Angptl2 Tg), which drives Angptl2 expression in endothelial cells but not monocytes/macrophages, showed accelerated plaque formation and vascular inflammation because of increased numbers of infiltrated macrophages in atheromatous plaques. Tie2-Angptl2 Tg mice alone did not develop plaques but exhibited endothelium-dependent vasodilatory dysfunction, likely because of decreased production of endothelial cell-derived nitric oxide. Conversely, Angptl2(-/-) mice exhibited less severe endothelial dysfunction than did wild-type mice when fed a high-fat diet. In vitro, Angptl2 activated proinflammatory nuclear factor-κB signaling in endothelial cells and increased monocyte/macrophage chemotaxis. CONCLUSIONS: Endothelial cell-derived Angptl2 accelerates vascular inflammation by activating proinflammatory signaling in endothelial cells and increasing macrophage infiltration, leading to endothelial dysfunction and atherosclerosis progression.

Perivascular adipose tissue-secreted angiopoietin-like protein 2 (Angptl2) accelerates neointimal hyperplasia after endovascular injury.

Much attention is currently focused on the role of perivascular adipose tissue in development of cardiovascular disease (CVD). Some researchers view it as promoting CVD through secretion of cytokines and growth factors called adipokines, while recent reports reveal that perivascular adipose tissue can exert a protective effect on CVD development. Furthermore, adiponectin, an anti-inflammatory adipokine, reportedly suppresses neointimal hyperplasia after endovascular injury, whereas such vascular remodeling is enhanced by pro-inflammatory adipokines secreted by perivascular adipose, such as tumor necrosis factor-α (TNF-α). These findings suggest that extent of vascular remodeling, a pathological process associated with CVD development, depends on the balance between pro- and anti-inflammatory adipokines secreted from perivascular adipose tissue. We previously demonstrated that angiopoietin-like protein 2 (Angptl2), a pro-inflammatory factor secreted by adipose tissue, promotes adipose tissue inflammation and subsequent systemic insulin resistance in obesity. Here, we examined whether Angptl2 secreted by perivascular adipose tissue contributes to vascular remodeling after endovascular injury in studies of transgenic mice expressing Angptl2 in adipose tissue (aP2-Angptl2 transgenic mice) and Angptl2 knockout mice (Angptl2(-/-) mice). To assess the role of Angptl2 secreted by perivascular adipose tissue on vascular remodeling after endovascular injury, we performed adipose tissue transplantation experiments using these mice. Wild-type mice with perivascular adipose tissue derived from aP2-Angptl2 mice exhibited accelerated neointimal hyperplasia after endovascular injury compared to wild-type mice transplanted with wild-type tissue. Conversely, vascular inflammation and neointimal hyperplasia after endovascular injury were significantly attenuated in wild-type mice transplanted with Angptl2(-/-) mouse-derived perivascular adipose tissue compared to wild-type mice transplanted with wild-type tissue. RT-PCR analysis revealed that mouse Angptl2 expression in perivascular adipose tissue was significantly increased by aging, hypercholesterolemia, and endovascular injury, all risk factors for coronary heart disease (CHD). Immunohistochemical and RT-PCR analysis of tissues from patients with CHD and from non-CHD patients indicated that ANGPTL2 expression in epicardial adipose tissue was unchanged. Interestingly, that analysis also revealed a positive correlation in ANGPTL2 and ADIPONECTIN expression in epicardial adipose tissue of non-CHD patients, a correlation not seen in CHD patients. However, in epicardial adipose tissue from CHD patients, ANGPTL2 expression was positively correlated with that of TNF-α, a correlation was not seen in non-CHD patients. These findings suggest that pro-inflammatory adipokines cooperatively accelerate CHD development and that maintaining a balance between pro- and anti-inflammatory adipokines likely protects non-CHD patients from developing CHD. Overall, our studies demonstrate that perivascular adipose tissue-secreted Angptl2 accelerates vascular inflammation and the subsequent CVD development.

Macrophage-derived angiopoietin-like protein 2 accelerates development of abdominal aortic aneurysm.

OBJECTIVE: Recently, we reported that angiopoietin-like protein 2 (Angptl2) functions in various chronic inflammatory diseases. In the present study, we asked whether Angptl2 and its associated chronic inflammation contribute to abdominal aortic aneurysm (AAA). METHODS AND RESULTS: Immunohistochemistry revealed that Angptl2 is abundantly expressed in infiltrating macrophages within the vessel wall of patients with AAA and in a CaCl(2)-induced AAA mouse model. When Angptl2-deficient mice were used in the mouse model, they showed decreased AAA development compared with wild-type mice, as evidenced by reduction in aneurysmal size, less severe destruction of vessel structure, and lower expression of proinflammatory cytokines and matrix metalloproteinase-9. However, no difference in the number of infiltrating macrophages within the aortic aneurysmal vessel wall was observed between genotypes. AAA development was also significantly suppressed in wild-type mice that underwent Angptl2-deficient bone marrow transplantation. Expression levels of proinflammatory cytokines and metalloproteinase-9 in Angptl2-deficient macrophages were significantly decreased, and those decreases were rescued by treatment of Angptl2 deficient macrophages with exogenous Angptl2. CONCLUSIONS: Macrophage-derived Angptl2 contributes to AAA development by inducing inflammation and degradation of extracellular matrix in the vessel wall, suggesting that targeting the Angptl2-induced inflammatory axis in macrophages could represent a new strategy for AAA therapy.

The endoplasmic reticulum stress-C/EBP homologous protein pathway-mediated apoptosis in macrophages contributes to the instability of atherosclerotic plaques.

OBJECTIVE: To elucidate whether and how the endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP) pathway in macrophages is involved in the rupture of atherosclerotic plaques. METHODS AND RESULTS: Increases in macrophage-derived foam cell death in coronary atherosclerotic plaques cause the plaque to become vulnerable, thus resulting in acute coronary syndrome. The ER stress-CHOP/growth arrest and DNA damage-inducible gene-153 (GADD153) pathway is induced in the macrophage-derived cells in atherosclerotic lesions and is involved in plaque formation. However, the role of CHOP in the final stage of atherosclerosis has not been fully elucidated. Many CHOP-expressing macrophages showed apoptosis in advanced ruptured atherosclerotic lesions in wild-type mice, whereas few apoptotic cells were observed in Chop(-/-) mice. The rupture of atherosclerotic plaques was significantly reduced in high cholesterol-fed Chop(-/-)/Apoe(-/-) mice compared with Chop(+/+)/Apoe(-/-) mice. Furthermore, using mice that underwent bone marrow transplantation, we showed that expression of CHOP in macrophages significantly contributes to the formation of ruptures. By using primary cultured macrophages, we further showed that unesterified free cholesterol derived from incorporated denatured low-density lipoprotein was accumulated in the ER and induced ER stress-mediated apoptosis in a CHOP-Bcl2-associated X protein (Bax) pathway-dependent manner. CONCLUSIONS: The ER stress-CHOP-Bax-mediated apoptosis in macrophages contributes to the instability of atherosclerotic plaques.

Early and Mid-Term Outcomes after Vascular Reconstruction for Patients with Lower-Extremity Soft-Tissue Malignant Tumors.

Objective: To evaluate limb-salvage surgery including vascular resection for lower-extremity soft-tissue sarcomas and carcinomas for adult patients. Materials and Methods: Eight consecutive patients (median age, 59 years) who underwent vascular replacement during surgery for malignant tumors in the lower limbs between November 2006 and March 2018 were evaluated. Patient data were retrospectively obtained in a computerized database. Arterial and venous reconstructions were performed for seven patients, with one additional patient receiving venous reconstruction only. Autologous-vein (n=6) and synthetic bypasses were used for arterial repairs, whereas only autologous veins were implanted for venous repairs. Results: Morbidity was 62.5%, and in-hospital mortality was 12.5%. At a median follow-up of 24 months, the primary patency rates of arterial and venous reconstructions were 85.7% and 62.5%, respectively. Limb salvage was achieved in all cases. Conclusion: Early and mid-term bypass patency rates, the high percentage of limb salvage, and the oncologic outcome underline the efficacy of en bloc resection of soft-tissue tumors involving major vessels of the lower limbs. The anticipated need for vascular resection and reconstruction should not be a contraindication to sarcoma and carcinoma resections. However, efforts to achieve better control over systemic spread are required for long-term survival.

Concomitant aorto-right subclavian artery bypass with off-pump coronary artery bypass grafting: a case report.

BACKGROUND: Atherosclerotic stenosis of the brachiocephalic artery sometimes occurs in patients with coronary artery disease, and can cause stroke during the perioperative period of coronary artery bypass grafting. CASE PRESENTATION: We describe the case of a 77-year old male with severe stenosis of the brachiocephalic artery and severe coronary artery disease. He successfully underwent aorto-right subclavian artery bypass that was performed concomitantly with off-pump coronary artery bypass. CONCLUSION: Concomitant aorto-subclavian artery bypass with off-pump coronary artery bypass grafting is a therapeutic option that minimizes the risk of perioperative stroke in patients with brachiocephalic artery stenosis and coronary artery disease.

Repair of left ventricular rupture in a patient with mitral annular calcification.

Left ventricular free wall rupture is a complication following acute myocardial infarction or mitral valve replacement. We report the case of a 56-year-old female patient with idiopathic left ventricular rupture confirmed by contrast-enhanced computed tomography (CT). CT also showed no coronary artery obstruction and severe mitral annular calcification. Left ventricular rupture was successfully repaired internally with bovine pericardium. Mitral valve replacement with annular decalcification was also performed.

Tricuspid Valve Repair With Artificial Chorda After Previous Ventricular Septal Defect Repair.

We evaluated a 49-year-old man with severe tricuspid valve regurgitation and coronary artery disease who had undergone congenital ventricular septal defect repair four decades previously. We found an enlarged, prolapsed commissure between the anterior and septal leaflets and a ruptured septal leaflet chorda. Two mattress sutures closed the commissure, with the leaflets' height matched by inverting the prolapsed site ventricularly. After implanting the annuloplasty band, we undertook chordal replacement using expanded polytetrafluoroethylene sutures. Artificial chorda length was determined using a small tourniquet and the saline test. Two coronary artery bypass grafts were also implanted. Postoperative echocardiography demonstrated no tricuspid regurgitation.

Nifedipine increases energy expenditure by increasing PGC-1α expression in skeletal muscle.

Nifedipine, an L-type calcium (Ca) channel blocker, is one of the most widely used Ca channel-blocking medications for hypertension. Previous studies have reported an association of nifedipine hypertensive treatment with decreased body weight in obese hypertensive humans and rat models. However, the precise mechanism underlying how nifedipine functions metabolically has not been elucidated. Here, we investigated the long-term effect of a non-hypotensive nifedipine dose using a mildly obese, endothelial NO synthase-deficient mouse model. Treating these mice with nifedipine decreased their body weight gain ratio, and white adipose tissue weight compared with the untreated controls. Metabolic analyses indicated that nifedipine treatment upregulated whole-body energy expenditure through increasing oxygen consumption and reducing the respiratory exchange ratio, suggesting that nifedipine promotes lipid oxidation rather than carbohydrate utilization. Furthermore, nifedipine treatment upregulated the expression of the peroxisome proliferator-activated receptor-γ coactivator -1α (PGC-1α) in skeletal muscle. Overall, these results suggest that a non-hypotensive dose of nifedipine has pleiotropic effects on energy expenditure that could ameliorate obesity.

Angiopoietin-like protein 2 promotes chronic adipose tissue inflammation and obesity-related systemic insulin resistance.

Recent studies of obesity have provided new insights into the mechanisms underlying insulin resistance and metabolic dysregulation. Numerous efforts have been made to identify key regulators of obesity-linked adipose tissue inflammation and insulin resistance. We found that angiopoietin-like protein 2 (Angptl2) was secreted by adipose tissue and that its circulating level was closely related to adiposity, systemic insulin resistance, and inflammation in both mice and humans. Angptl2 activated an inflammatory cascade in endothelial cells via integrin signaling and induced chemotaxis of monocytes/macrophages. Constitutive Angptl2 activation in vivo induced inflammation of the vasculature characterized by abundant attachment of leukocytes to the vessel walls and increased permeability. Angptl2 deletion ameliorated adipose tissue inflammation and systemic insulin resistance in diet-induced obese mice. Conversely, Angptl2 overexpression in adipose tissue caused local inflammation and systemic insulin resistance in nonobese mice. Thus, Angptl2 is a key adipocyte-derived inflammatory mediator that links obesity to systemic insulin resistance.