Effects of tafamidis on the left ventricular and left atrial strain in patients with wild-type transthyretin cardiac amyloidosis.

Aims: Although tafamidis is used in patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA), its specific effect on cardiac function is unclear. Thus, this study aimed to investigate the effect of tafamidis on left atrial (LA) and left ventricular function using speckle-tracking echocardiography for 1 year of treatment in patients with ATTRwt-CA.

Methods And Results: We included 23 patients (mean age, 76 years) with ATTRwt-CA confirmed via biopsy.

Comparison of Effectiveness and Safety Among 3 Direct Oral Anticoagulants in Patients With Venous Thromboembolism - A Single-Center Retrospective Study.

Direct oral anticoagulants (DOACs), including edoxaban, rivaroxaban, and apixaban, are administered for the treatment of venous thromboembolism (VTE) in Japan. However, only a few reports have compared the effectiveness and safety of these DOACs. We retrospectively enrolled 702 patients who received DOACs for VTE treatment between September 2014 and March 2020.

Pathological features of biopsied myocardium in patients clinically diagnosed with peripartum cardiomyopathy.

The etiology of peripartum cardiomyopathy (PPCM) is unknown. Therefore, we evaluated the etiology of patients clinically diagnosed with PPCM using endomyocardial biopsy. We studied five patients diagnosed with PPCM following endomyocardial biopsy (age, 28-42 years; mean age, 35 years).

Regeneration of the ureter using a scaffold-free live-cell structure created with the bio-three-dimensional printing technique.

Ureteral strictures, which can be caused by ureteral injury, radiation therapy, ureterolithiasis, urinary tract infections, and ureteral endometriosis, typically require ureteral reconstruction. Although tissue engineering, autologous alternative tissue transplantation, and surgical techniques applying various flaps have been carried out for ureteral regeneration, all with some success, each method has its advantages and disadvantages. As an alternative, we created the first artificial ureter structures using only live cells and grafted them into healthy rat ureters.

Comparison of Dasatinib- and Imatinib-Related Cardiotoxic Adverse Events in Japanese Patients With Chronic Myeloid Leukemia and Gastrointestinal Stromal Tumor.

Despite the beneficial effects of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML), they may also cause adverse events (AEs), especially cardiovascular toxicity. The incidence of TKI-induced AEs may vary among ethnic groups, and there is little specific information for Japanese patients. Sixty-nine consecutive patients who were started on treatment with dasatinib (n=25) or imatinib (n=44) for CML or gastrointestinal stromal tumor (GIST) between December 2008 and December 2019 were retrospectively recruited to the study.

Febuxostat, a Xanthine Oxidase Inhibitor, Decreased Macrophage Matrix Metalloproteinase Expression in Hypoxia.

Macrophages in the atheroma region produce matrix metalloproteinases (MMPs) and decrease plaque stability. Tissue oxygen tension decreases in the arterial wall of the atherosclerotic region. Hypoxia inducible factor (HIF)-1α plays a critical role in the transcriptional activation of hypoxia inducible genes.

Effectiveness and safety of oral direct factor Xa inhibitors for the treatment of venous thromboembolism in patients with cancer and/or older age.

Venous thromboembolism (VTE) is a multifactorial disease. Cancer and older age are risk factors for both recurrent VTE and bleeding under anticoagulant therapy. Oral direct factor Xa inhibitors (Xa inhibitors) have been widely used to treat VTE.

Comparison of the effects of edoxaban, an oral direct factor Xa inhibitor, on venous thromboembolism between patients with and without cancer.

Background: Venous thromboembolism (VTE) is a frequent and serious complication of cancer. The current guidelines in the USA and Europe recommend low-molecular weight heparin (LMWH) for the treatment of cancer-associated VTE. In Japan, LMWH is not given for the treatment of VTE; instead edoxaban, an oral direct factor Xa inhibitor, was approved for the treatment of VTE in September 2014.

Jagged-1 Signaling in the Bone Marrow Microenvironment Promotes Endothelial Progenitor Cell Expansion and Commitment of CD133+ Human Cord Blood Cells for Postnatal Vasculogenesis.

Notch signaling is involved in cell fate decisions during murine vascular development and hematopoiesis in the microenvironment of bone marrow. To investigate the close relationship between hematopoietic stem cells and human endothelial progenitor cells (EPCs) in the bone marrow niche, we examined the effects of Notch signals [Jagged-1 and Delta-like ligand (Dll)-1] on the proliferation and differentiation of human CD133+ cell-derived EPCs. We established stromal systems using HESS-5 murine bone marrow cells transfected with human Jagged-1 (hJagged-1) or human Dll-1 (hDll-1).

Adipose-derived regenerative cell therapy inhibits the progression of monocrotaline-induced pulmonary hypertension in rats.

Aims: Functional and structural changes in pulmonary vasculature characterize pulmonary arterial hypertension (PAH) and the prognosis of advanced PAH remains poor despite progress in pharmacotherapy. Adipose-derived regenerative cells (ADRCs) promote cell regeneration at pathological sites and comprise a novel therapy for ailments of various organs. We investigated the effects of ADRC therapy in rat models of monocrotaline (MCT)-induced pulmonary hypertension (PH) and the underlying mechanisms.

Cyclophosphamide-induced cardiotoxicity with a prolonged clinical course diagnosed on an endomyocardial biopsy.

A 31-year-old woman with primary mediastinal large B-cell lymphoma refractory to conventional chemotherapy was treated with high-dose chemotherapy containing cyclophosphamide (CY). Subsequently, she was treated with auto peripheral blood stem cell transplantation. Although a complete remission was obtained, heart failure developed two months later.

Pivotal role of lnk adaptor protein in endothelial progenitor cell biology for vascular regeneration.

Despite the fact that endothelial progenitor cells (EPCs) are important for postnatal neovascularization, their origins, differentiation, and modulators are not clear. Here, we demonstrate that Lnk, a negative regulator of hematopoietic stem cell proliferation, controls endothelial commitment of c-kit(+)/Sca-1(+)/Lineage(-) (KSL) subpopulations of bone marrow cells. The results of EPC colony-forming assays reveal that small (primitive) EPC colony formation by CD34(-) KSLs and large (definitive) EPC colony formation by CD34((dim)) KSLs are more robust in lnk(-/-) mice.

Lesion-targeted thrombopoietin potentiates vasculogenesis by enhancing motility and enlivenment of transplanted endothelial progenitor cells via activation of Akt/mTOR/p70S6kinase signaling pathway.

Thrombopoietin (TPO), a physiological regulator of megakaryocyte and platelet development, is a multifunctional positive regulator in early hematopoiesis by hematopoietic stem cells. In this study, we investigated the effect of TPO on endothelial progenitor cells (EPCs) for therapeutic vasculogenesis in vitro and in vivo, and the intracellular signaling mechanism exerting the activity of EPCs. 7-day culture-expanded EPCs derived from human peripheral blood mononuclear cells were applied to each assay.

Specific Jagged-1 signal from bone marrow microenvironment is required for endothelial progenitor cell development for neovascularization.

Background: Despite accumulating evidence that proves the pivotal role of endothelial progenitor cells (EPCs) in ischemic neovascularization, the key signaling cascade that regulates functional EPC kinetics remains unclear.

Methods And Results: In this report, we show that inactivation of specific Jagged-1 (Jag-1)-mediated Notch signals leads to inhibition of postnatal vasculogenesis in hindlimb ischemia via impairment of proliferation, survival, differentiation, and mobilization of bone marrow-derived EPCs. Bone marrow-derived EPCs obtained from Jag-1-/- mice, but not Delta-like (Dll)-1-/- mice, demonstrated less therapeutic potential for ischemic neovascularization than EPCs from the wild type.

Nicotine enlivenment of blood flow recovery following endothelial progenitor cell transplantation into ischemic hindlimb.

Nicotine has been demonstrated to stimulate postnatal angiogenesis, having an antiapoptotic effect on endothelial cells. Given the extent of this angiogenesis-promoting effect, we hypothesized that nicotine may also stimulate postnatal vasculogenesis on endothelial progenitor cells (EPCs). Our analyses reveal some intriguing results using an in vitro assay with 2 x 10(-6) M of nicotine (smoker's average nicotine concentration and the dose of nicotine replacement therapy).

Estrogen-mediated endothelial progenitor cell biology and kinetics for physiological postnatal vasculogenesis.

Estrogen has been demonstrated to promote therapeutic reendothelialization after vascular injury by bone marrow (BM)-derived endothelial progenitor cell (EPC) mobilization and phenotypic modulation. We investigated the primary hypothesis that estrogen regulates physiological postnatal vasculogenesis by modulating bioactivity of BM-derived EPCs through the estrogen receptor (ER), in cyclic hormonally regulated endometrial neovascularization. Cultured human EPCs from peripheral blood mononuclear cells (PB-MNCs) disclosed consistent gene expression of ER alpha as well as downregulated gene expressions of ER beta.

Endothelial progenitor cells for postnatal vasculogenesis.

Bone marrow-derived endothelial progenitor cells (EPCs) are present in the systemic circulation, are augmented in response to certain cytokines and/or tissue ischemia, and are home to--as well as incorporate into--sites of neovascularization. On the basis of these aspects, EPCs have attractive potential therapeutic applications for cardiovascular ischemic diseases as a novel cell-based strategy, mainly via a vasculogenesis mechanism. This review provides an update of the biology of EPCs, as well as highlighting the potential use of these cells for therapeutic regeneration.

Establishment of a functionally active collagen-binding vascular endothelial growth factor fusion protein in situ.

Objective: Tissue regeneration requires both growth factor and extracellular matrix such as collagen, serving as a scaffold for cell growth. We established FNCBD-VEGF121, consisting of the fibronectin collagen-binding domain (FNCBD) and vascular endothelial growth factor (VEGF) 121, and investigated its properties.

Methods And Results: FNCBD-VEGF121 specifically bound to gelatin and type I, II, III, IV, and V collagen.