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1.
JACC Adv ; 3(4): 100887, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38939653

RESUMEN

Background: A treatment strategy for congenital heart defects with moderate to severe pulmonary arterial hypertension (PAH) has not been established. Objectives: The purpose of this study was to identify patients in whom a treat and repair strategy was considered and to examine pretreatment variables associated with successful defect repair. Methods: Patients with atrial or ventricular septal defect and PAH (pulmonary vascular resistance [PVR] ≥ 5 Wood units) eligible for the treat and repair strategy were included. Hemodynamics among pretreatment, pre-repair, and post-defect repair were compared. Clinical outcomes in patients with or without defect repair were also compared. Clinical outcomes included all-cause death, hospitalization for worsening pulmonary hypertension, and lung transplantation. Results: Among 25 eligible for the treat and repair strategy, 20 underwent successful repair (repaired group) and 5 did not have a repair (unrepaired group). In the repaired group, PVR significantly decreased from 9.6 ± 2.6 WU at pretreatment to 5.0 ± 3.4 pre-repair (ß coefficient -4.6 [95% CI: -5.9 to -3.3]). The pulmonary to systemic blood flow ratio (Qp/Qs) increased from 1.5 ± 0.6 at pretreatment to 2.4 ± 1.3 pre-repair (ß coefficient 0.9 [95% CI: 0.4-1.38]). In the unrepaired group, pretreatment PVR decreased with treatment; however, PVR remained elevated. Qp/Qs did not change between pretreatment and post-treatment. The repaired group had a better prognosis than the unrepaired group (HR 0.092 [95% CI: 0.009-0.905]). Pretreatment mean pulmonary artery pressure, PVR, Qp/Qs, and arterial oxygen saturations were associated with undergoing defect repair. Conclusions: In this small cohort, a treat and repair strategy was successfully used in a significant proportion of the patients with congenital heart defects with moderate to severe PAH.

2.
Nutrients ; 16(12)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38931242

RESUMEN

Diabetes mellitus (DM) is a major risk and prognostic factor for heart failure (HF). Insulin resistance (IR) is an important component of DM, but the relationship between IR and HF prognosis has not yet been established across a wide variety of HF populations. We retrospectively evaluated the relationship between IR and clinical outcomes of HF patients at our hospital between 2017 and 2021. IR was defined as a homeostatic model assessment of IR (HOMA-IR) index ≥ 2.5, calculated from fasting blood glucose and insulin concentrations. The primary outcome was a composite of all-cause death and hospitalisation for HF (HHF). Among 682 patients included in the analyses, 337 (49.4%) had IR. The median age was 70 [interquartile range (IQR): 59-77] years old, and 66% of the patients were men. Among the patients, 41% had a left ventricular ejection fraction below 40%, and 32% had DM. The median follow-up period was 16.5 [IQR: 4.4-37.3] months. IR was independently associated with the primary outcome (HR: 1.91, 95% CI: 1.39-2.62, p < 0.0001), death (hazard ratio [HR]: 1.86, 95% confidence interval [CI]: 1.28-2.83, p < 0.01), and HHF (HR: 1.91, 95% CI: 1.28-2.83, p < 0.01). HOMA-IR is an independent prognostic factor of HF in a wide variety of HF populations.


Asunto(s)
Insuficiencia Cardíaca , Resistencia a la Insulina , Humanos , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/sangre , Masculino , Femenino , Anciano , Persona de Mediana Edad , Pronóstico , Japón/epidemiología , Estudios Retrospectivos , Glucemia/metabolismo , Hospitalización/estadística & datos numéricos , Insulina/sangre , Factores de Riesgo , Volumen Sistólico
3.
J Reprod Dev ; 70(4): 223-228, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-38763744

RESUMEN

Embryonic transfer of bovine blastocysts produced by in vitro fertilization is widely utilized-despite a compromised conception rate. It has been suggested that a set of four evaluation criteria for judging the quality of embryos, based on the timing of early cleavages and proper morphologies of embryos, can effectively predict pregnancy success. These blastocysts are hereafter referred to as four-criteria-compliant blastocysts. The same criteria should be used to modify the culture media to improve embryo quality. For example, culture media is often supplemented with nonessential amino acids (NEAA) at a uniform concentration despite the major variation in their concentration in the oviductal fluid. In the present study, the effects of the embryo culture medium, namely CR1, supplemented with all seven MEM NEAA or six of them, excluding one at a time, were examined. All media, except for the medium that did not contain proline and serine, tended to improve the efficiency of producing four-criteria-compliant blastocysts, and excluding alanine was particularly effective. The absence of alanine resulted in the rapid occurrence of the first cleavage and pronuclear formation of fertilized oocytes in the alanine-free medium compared to that in the medium containing alanine. These results suggested that alanine hinders certain events involved in the progression of early embryogenesis, which is necessary to achieve the four criteria that provide a benchmark for pregnancy. Therefore, a significantly higher percentage of embryos satisfied the recommended criteria and developed into four-criteria-compliant blastocysts when developed in alanine-free medium than in alanine-containing medium.


Asunto(s)
Alanina , Blastocisto , Medios de Cultivo , Técnicas de Cultivo de Embriones , Desarrollo Embrionario , Fertilización In Vitro , Oocitos , Animales , Bovinos , Femenino , Fertilización In Vitro/veterinaria , Fertilización In Vitro/métodos , Alanina/farmacología , Técnicas de Cultivo de Embriones/veterinaria , Técnicas de Cultivo de Embriones/métodos , Oocitos/efectos de los fármacos , Oocitos/metabolismo , Desarrollo Embrionario/efectos de los fármacos , Blastocisto/efectos de los fármacos , Embarazo , Aminoácidos/farmacología , Aminoácidos/metabolismo
4.
Circ J ; 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38556267
6.
J Reprod Dev ; 70(1): 42-48, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38246613

RESUMEN

Embryonic transfer of bovine blastocysts produced using in vitro fertilization (IVF) is widely used, although the challenge of compromised conception rates remains. Using bovine oviduct epithelial cells (BOEC) to improve embryo culture conditions has attracted attention, particularly since the recent discovery of extracellular vesicles from BOEC. The selection of embryos for transfer has also been the subject of various studies, and a set of evaluation criteria to predict pregnancy success has been suggested, in which the embryos are judged by their kinetics and morphology at the early stages. In the present study, we established a spontaneously immortalized BOEC line (SI-BOEC) and examined the effects of conditioned medium on IVF embryos, focusing on the results of the recommended criteria. A modified KSOM (mKSOM) was used to prepare conditioned media. Presumptive zygotes were cultured in mKSOM (control), SI-BOEC-conditioned medium, mKSOM supplemented with sediment (pellet) collected after the ultracentrifugation of the conditioned medium (mKSOM/sediment), and the supernatant. A significantly higher percentage of embryos satisfied the recommended criteria when grown in the conditioned medium than in the mKSOM. A higher proportion of embryos developed into blastocysts after achieving the four criteria. A similar tendency was observed when grown in mKSOM/sediment compared to mKSOM; however, this was not observed in the supernatant. Vesicles with a size similar to that of exosomes were observed in the sediment. In conclusion, the culture medium conditioned by SI-BOEC promoted the production of bovine blastocysts that satisfied the four evaluation criteria recommended for embryo selection.


Asunto(s)
Trompas Uterinas , Oviductos , Embarazo , Femenino , Humanos , Bovinos , Animales , Medios de Cultivo Condicionados/farmacología , Medios de Cultivo Condicionados/metabolismo , Oviductos/metabolismo , Embrión de Mamíferos , Células Epiteliales , Blastocisto , Fertilización In Vitro/veterinaria
7.
Intern Med ; 63(5): 671-676, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37468249

RESUMEN

A 34-year-old woman with pulmonary arterial hypertension (PAH) was admitted to the hospital. She had been diagnosed with PAH three years earlier and treated with triple vasodilator therapy. She was positive for anti-U1 ribonucleoprotein antibodies but did not show any other symptoms associated with autoimmune diseases. Corticosteroid and cyclophosphamide therapy was administered, suspecting the involvement of immunological pathophysiology. After 3 weeks, the mean pulmonary artery pressure decreased from 50 to 38 mmHg without any change in the vasodilators. Immunosuppressive therapy was effective in this patient with PAH with an anti-U1 ribonucleoprotein-antibody-positive response and might be an option for patients with these specific features.


Asunto(s)
Hipertensión Arterial Pulmonar , Femenino , Humanos , Adulto , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Anticuerpos Antinucleares , Corticoesteroides , Ribonucleoproteínas
9.
Front Cardiovasc Med ; 10: 1212882, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37731527

RESUMEN

Aims: Limited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categories based on severity: (1) no intimal thickening, (2) cellular thickening of the intima, (3) fibrous thickening of the intima, and (4) destruction of the tunica media, with the overall grade expressed as an additive mean of these scores. This study aimed to investigate the relationship between IPVD and the long-term outcome of CHD-PAH. Methods: This retrospective study examined lung pathology images of 764 patients with CHD-PAH aged <20 years whose lung specimens were submitted to the Japanese Research Institute of Pulmonary Vasculature for pulmonary pathological review between 2001 and 2020. Clinical information was collected retrospectively by each attending physician. The primary endpoint was cardiovascular death. Results: The 5-year, 10-year, 15-year, and 20-year cardiovascular death-free survival rates for all patients were 92.0%, 90.4%, 87.3%, and 86.1%, respectively. The group with an IPVD of ≥2.0 had significantly poorer survival than the group with an IPVD <2.0 (P = .037). The Cox proportional hazards model adjusted for the presence of congenital anomaly syndromes associated with pulmonary hypertension, and age at lung biopsy showed similar results (hazard ratio 4.46; 95% confidence interval: 1.45-13.73; P = .009). Conclusions: The IPVD scoring system is useful for predicting the long-term outcome of CHD-PAH. For patients with an IPVD of ≥2.0, treatment strategies, including choosing palliative procedures such as pulmonary artery banding to restrict pulmonary blood flow and postponement of intracardiac repair, should be more carefully considered.

10.
Pulm Circ ; 13(3): e12286, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37705961

RESUMEN

Pulmonary arterial hypertension is a life-threatening disease that coexists with right heart failure. We evaluated the relationship between malnutrition and prognosis in patients with pulmonary arterial hypertension, as malnutrition is known as a prognosis determinant in chronic heart failure. We retrospectively reviewed data of patients with pulmonary arterial hypertension before treatment. The Geriatric Nutritional Risk Index, Prognostic Nutritional Index, and Controlling Nutritional Status scores on the day of diagnosis were calculated to assess the nutritional status. Clinical endpoints were defined as composite outcomes of all-cause death or lung transplantation. Eighty patients were enrolled (mean age, 50 years; 23 men). The mean pulmonary arterial pressure was 47 ± 19 mmHg, Geriatric Nutritional Risk Index was 99.9 ± 12.0, and Prognostic Nutritional Index was 46.3 ± 10.0. The median Controlling Nutritional Status score was 2 (1-4). During the median 5.5-year follow-up period, 28 composite events occurred. Kaplan-Meier analysis demonstrated significant differences in the incidence of clinical endpoints between groups divided by each median Geriatric Nutritional Risk Index, Prognostic Nutritional Index, and Controlling Nutritional Status score (p = 0.007, 0.039, and 0.010, respectively). In multivariate Cox regression analysis, clinical endpoints were significantly associated with Geriatric Nutritional Risk Index (hazard ratio: 0.953, 95% confidence interval: 0.918-0.990), Prognostic Nutritional Index (hazard ratio: 0.942, 95% confidence interval: 0.892-0.996), and Controlling Nutritional Status score (hazard ratio: 1.230, 95% confidence interval: 1.056-1.433) after adjustment for factors associated in univariate Cox regression analysis. Malnutrition at diagnosis is a useful prognostic predictor for patients with pulmonary arterial hypertension.

11.
Front Cardiovasc Med ; 10: 1261330, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37745108

RESUMEN

Introduction: Transplantation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is a promising treatment for heart failure. Information on long-term cell engraftment after transplantation is clinically important. However, clinically applicable evaluation methods have not yet been established. Methods: In this study, to noninvasively assess transplanted cell engraftment, human SLC5A5, which encodes a sodium/iodide symporter (NIS) that transports radioactive tracers such as 125I, 18F-tetrafluoroborate (TFB), and 99mTc-pertechnetate (99mTcO4-), was transduced into human induced pluripotent stem cells (iPSCs), and nuclear medicine imaging was used to track engrafted human iPSC-CMs. Results: To evaluate the pluripotency of NIS-expressing human iPSCs, they were subcutaneously transplanted into immunodeficient rats. Teratomas were detected by 99mTcO4- single photon emission computed tomography (SPECT/CT) imaging. NIS expression and the uptake ability of 125I were maintained in purified human iPSC-CMs. NIS-expressing human iPSC-CMs transplanted into immunodeficient rats could be detected over time using 99mTcO4- SPECT/CT imaging. Unexpectedly, NIS expression affected cell proliferation of human iPSCs and iPSC-derived cells. Discussion: Such functionally designed iPSC-CMs have potential clinical applications as a noninvasive method of grafted cell evaluation, but further studies are needed to determine the effects of NIS transduction on cellular characteristics and functions.

12.
J Clin Med ; 12(15)2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37568430

RESUMEN

BACKGROUND: The metabolic state of pulmonary artery smooth muscle cells (PASMCs) from patients with pulmonary arterial hypertension (PAH) is not well understood. In this study, we examined the balance between glycolysis and mitochondrial respiration in non-PAH-PASMCs and PAH-PASMCs under normoxia and hypoxia. METHODS: We investigated the enzymes involved in glycolysis and mitochondrial respiration, and studied the two major energy-yielding pathways (glycolysis and mitochondrial respiration) by measuring extracellular acidification rate (ECAR) and cellular oxygen consumption rate (OCR) using the Seahorse extracellular flux technology. RESULTS: Under both normoxia and hypoxia, the mRNA and protein levels of pyruvate dehydrogenase kinase 1 and pyruvate dehydrogenase were increased in PAH-PASMCs compared with non-PAH-PASMCs. The mRNA and protein levels of lactate dehydrogenase, as well as the intracellular lactate concentration, were also increased in PAH-PASMCs compared with non-PAH-PASMCs under normoxia. However, these were not significantly increased in PAH-PASMCs compared with non-PAH-PASMCs under hypoxia. Under normoxia, ATP production was significantly lower in PAH-PASMCs (59 ± 5 pmol/min) than in non-PAH-PASMCs (70 ± 10 pmol/min). On the other hand, ATP production was significantly higher in PAH-PASMCs (31 ± 5 pmol/min) than in non-PAH-PASMCs (14 ± 3 pmol/min) under hypoxia. CONCLUSIONS: There is an underlying change in the metabolic strategy to generate ATP production under the challenge of hypoxia.

13.
Eur Heart J Case Rep ; 7(5): ytad214, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37324501

RESUMEN

Background: Impella 5.0 is currently used as a temporary mechanical circulatory support device in cardiogenic shock (CS). However, Impella 5.0 implantation for the systemic right ventricle (sRV) has not been well documented. Case summary: A 50-year-old man with atrial switch for dextro-transposition of the great arteries was transferred to our hospital for the treatment of embolic acute myocardial infarction of the left main trunk lesion with CS. To stabilize haemodynamics, we implanted Impella 5.0 via the left subclavian artery in the sRV. After optimal medical therapy initiation and gradual weaning of Impella 5.0, Impella 5.0 was successfully explanted. An electrocardiogram was obtained, which showed complete right branch block with a QRS duration of 172 ms. Acute invasive haemodynamic evaluation of cardiac resynchronization therapy (CRT) pacing showed that dP/dt increased from 497 to 605 mmHg/s (21.7% improvement), and hybrid cardiac resynchronization therapy defibrillator (CRTD) with a sRV epicardial lead was subsequently implanted. The patient was discharged without inotropic support. Discussion: Coronary artery embolism is a rare but serious complication of dextro-transposition of the great arteries after atrial switch operations. Impella 5.0 implantation is a feasible bridge strategy for refractory CS due to sRV failure. Although CRT implantation in patients with sRV is controversial, an acute invasive haemodynamic evaluation can help assess its potential benefits.

14.
JAMA Cardiol ; 8(8): 792, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37342027

RESUMEN

This case report describes a woman diagnosed with Takayasu arteritis after presenting with a 2-month history of dyspnea and pulmonary artery hypertension.


Asunto(s)
Hipertensión Pulmonar , Arteritis de Takayasu , Humanos , Femenino , Arteritis de Takayasu/complicaciones , Arteritis de Takayasu/diagnóstico , Hipertensión Pulmonar/complicaciones
15.
J Cardiol Cases ; 27(3): 124-127, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36910040

RESUMEN

A 46-year-old woman with a history of repeated thromboembolic stroke and anti-phospholipid antibody syndrome was referred to our hospital. Saline contrast transthoracic echocardiography showed that microbubbles appeared in the left atrium within 4 heartbeats. Thus, she was initially suspected as having a patent foramen ovale with associated paradoxical embolism. However, no evidence of patent foramen ovale or atrial septal defect could be found using transesophageal echocardiography. Saline contrast transesophageal echocardiography showed that microbubbles flowed into the left atrium through the left superior pulmonary vein. Ultimately, she was diagnosed as having a pulmonary arteriovenous malformation located at the upper left pulmonary lobe using contrast computed tomography and pulmonary artery angiography. Pulmonary arteriovenous malformations are typically located in the lower lobe of either lung and, in bubble studies, contrast appears in the left atrium after 4 heartbeats. Here, the pulmonary arteriovenous malformation was in the upper lobe, and contrast appeared in the left atrium at an earlier time point: one associated with patent foramen ovale. These findings made it difficult to differentiate the two diseases initially. This case suggests that pulmonary arteriovenous malformation should be carefully considered, even if microbubbles appear in the left atrium early on a saline contrast transthoracic echocardiograph. Learning objective: Pulmonary arteriovenous malformation occasionally appears in the upper lobe. In these cases, microbubbles may appear in the left atrium after detection in the right atrium with a time-course that is suggestive of a patent foramen ovale. Therefore, diagnosis should be carefully confirmed by using other multimodal imaging tests, such as transesophageal echocardiography, contrast computed tomography, or pulmonary artery angiography.

16.
Nutrients ; 15(3)2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36771454

RESUMEN

Cardiovascular diseases and liver diseases are closely related. Non-alcoholic fatty liver disease has the same risk factors as those for atherosclerotic cardiovascular disease and may also be a risk factor for atherosclerotic cardiovascular disease on its own. Heart failure causes liver fibrosis, and liver fibrosis results in worsened cardiac preload and congestion. Although some previous reports regard the association between cardiovascular diseases and liver disease, the management strategy for liver disease in patients with cardiovascular diseases is not still established. This review summarized the association between cardiovascular diseases and liver disease. In patients with non-alcoholic fatty liver disease, the degree of liver fibrosis progresses with worsening cardiovascular prognosis. In patients with heart failure, liver fibrosis could be a prognostic marker. Liver stiffness assessed with shear wave elastography, the fibrosis-4 index, and non-alcoholic fatty liver disease fibrosis score is associated with both liver fibrosis in patients with liver diseases and worse prognosis in patients with heart failure. With the current population ageing, the importance of management for cardiovascular diseases and liver disease has been increasing. However, whether management and interventions for liver disease improve the prognosis of cardiovascular diseases has not been fully understood. Future investigations are needed.


Asunto(s)
Cardiólogos , Enfermedades Cardiovasculares , Insuficiencia Cardíaca , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/patología , Cirrosis Hepática/etiología , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/patología , Hígado/patología
17.
Int J Mol Sci ; 24(3)2023 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-36768243

RESUMEN

Transthyretin cardiac amyloidosis (ATTR-CA) is characterized by high 99mTc-labeled bone tracer uptake in the heart. However, the mechanism of bone tracer uptake into the heart remains controversial. Since bone tracer uptake into metastatic bone tumors is thought to be associated with increased bone metabolism, we examined 99mTc-pyrophosphate (PYP) scintigraphy findings, endomyocardial biopsy (EMB) tissue findings, and the expression of bone metabolism-related genes in the EMB tissues in patients with ATTR-CA, amyloid light-chain cardiac amyloidosis (AL-CA), and noncardiac amyloidosis (non-CA) in this study. The uptake of 99mTc-PYP in the heart was significantly higher in the ATTR-CA patients than in the AL-CA and non-CA patients. A higher percentage of ATTR-CA EMB tissue showed von Kossa-positive microparticles: ATTR-CA, 62%; AL-CA, 33%; and non-CA, 0%. Calcified microparticles were identified using transmission electron microscopy. However, none of the osteogenic marker genes, osteoclastic marker genes, or phosphate/pyrophosphate-related genes were upregulated in the EMB samples from ATTR-CA patients compared to those from AL-CA and non-CA patients. These results suggest that active calcification-promoting mechanisms are not involved in the microcalcification observed in the heart in ATTR-CA. The mechanisms explaining bone tracer uptake in the heart, which is stronger than that in the ribs, require further investigation.


Asunto(s)
Amiloidosis , Calcinosis , Cardiomiopatías , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Humanos , Difosfatos , Prealbúmina/genética , Cardiomiopatías/diagnóstico por imagen , Cardiomiopatías/patología , Radiofármacos
18.
Intern Med ; 62(9): 1319-1322, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-36130891

RESUMEN

A 59-year-old man with a high level of antinuclear antibody received nivolumab and ipilimumab plus chemotherapy for lung cancer. Two weeks after the second course, he was admitted with a fever and severe fatigue. Laboratory studies showed elevated markers of myocardial damage, and a myocardial biopsy showed inflammatory cell infiltration, damaged myocardial fibers. Myocarditis was diagnosed as an immune-related adverse event (irAE), and high-dose corticosteroids were initiated. However, his cardiac function rapidly worsened, and he died on the fifth day after admission. There is no established treatment strategy for fulminant myocarditis as an irAE, and the further exploration of viable treatment strategies is required.


Asunto(s)
Antineoplásicos Inmunológicos , Carcinoma , Neoplasias Pulmonares , Miocarditis , Masculino , Humanos , Persona de Mediana Edad , Nivolumab/uso terapéutico , Ipilimumab/efectos adversos , Miocarditis/patología , Antineoplásicos Inmunológicos/efectos adversos , Neoplasias Pulmonares/patología , Pulmón/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
19.
Sci Rep ; 12(1): 15449, 2022 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-36104378

RESUMEN

Sodium-glucose cotransporter 2 inhibitors could reduce cardiovascular events in patients with heart failure irrespective of diabetes status. In this prespecified sub-analysis of randomised-controlled trial, we investigated the efficacy of luseogliflozin (2.5 mg daily), a sodium-glucose cotransporter 2 inhibitor, with that of voglibose (0.6 mg daily), an alpha-glucosidase inhibitor, on high-risk lipid profile and inflammatory markers in patients with type-2 diabetes and heart failure. Among the 157 patients studied, there were no significant differences in the mean malondialdehyde LDL or small-dense LDL cholesterol levels between the luseogliflozin and voglibose groups (percent change: 0.2% vs. - 0.6%, p = 0.93; - 1.7% vs. - 8.6%, p = 0.21) after 12 weeks in comparison to levels at the baseline. No significant difference was observed between the two groups in the adiponectin and high-sensitivity C-reactive protein levels after 12 weeks compared to the baseline levels (percent change, - 1.6% vs. - 4.0% and 22.5% vs. 10.0%; p = 0.52 and p = 0.55, respectively). In conclusion, in patients with type-2 diabetes and heart failure, compared to voglibose, luseogliflozin did not significantly improve the high-risk lipoprotein profile including malondialdehyde LDL and small-dense LDL cholesterol or the levels of inflammatory markers, including adiponectin and high-sensitivity C-reactive protein.Trial registration: Trial number: UMIN-CTR, UMIN000018395; Registered 23 July 2015; URL: https://www.umin.ac.jp/ctr/index.htm .


Asunto(s)
Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Adiponectina , Biomarcadores , Proteína C-Reactiva , LDL-Colesterol , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucosa , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Inositol/análogos & derivados , Malondialdehído , Sodio , Sorbitol/análogos & derivados
20.
Front Cardiovasc Med ; 9: 904215, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35845076

RESUMEN

Background: Abdominal aortic aneurysm (AAA) is a life-threatening disease that lacks effective preventive therapies. This study aimed to evaluate the effect of pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPARα) agonist, on AAA formation and rupture. Methods: Experimental AAA was induced by subcutaneous angiotensin II (AngII) infusion in ApoE - / - mice for 4 weeks. Pemafibrate (0.1 mg/kg/day) was administered orally. Dihydroethidium staining was used to evaluate the reactive oxygen species (ROS). Results: The size of the AngII-induced AAA did not differ between pemafibrate- and vehicle-treated groups. However, a decreased mortality rate due to AAA rupture was observed in pemafibrate-treated mice. Pemafibrate ameliorated AngII-induced ROS and reduced the mRNA expression of interleukin-6 and tumor necrosis factor-α in the aortic wall. Gelatin zymography analysis demonstrated significant inhibition of matrix metalloproteinase-2 activity by pemafibrate. AngII-induced ROS production in human vascular smooth muscle cells was inhibited by pre-treatment with pemafibrate and was accompanied by an increase in catalase activity. Small interfering RNA-mediated knockdown of catalase or PPARα significantly attenuated the anti-oxidative effect of pemafibrate. Conclusion: Pemafibrate prevented AAA rupture in a murine model, concomitant with reduced ROS, inflammation, and extracellular matrix degradation in the aortic wall. The protective effect against AAA rupture was partly mediated by the anti-oxidative effect of catalase induced by pemafibrate in the smooth muscle cells.

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