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1.
Atherosclerosis ; 384: 117150, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37290980

RESUMO

BACKGROUND AND AIMS: Despite increased clinical interest in lipoprotein(a) (Lp(a)), many questions remain about the molecular mechanisms by which it contributes to atherosclerotic cardiovascular disease. Existing murine transgenic (Tg) Lp(a) models are limited by low plasma levels of Lp(a) and have not consistently shown a pro-atherosclerotic effect of Lp(a). METHODS: We generated Tg mice expressing both human apolipoprotein(a) (apo(a)) and human apoB-100, with pathogenic levels of plasma Lp(a) (range 87-250 mg/dL). Female and male Lp(a) Tg mice (Tg(LPA+/0;APOB+/0)) and human apoB-100-only controls (Tg(APOB+/0)) (n = 10-13/group) were fed a high-fat, high-cholesterol diet for 12 weeks, with Ldlr knocked down using an antisense oligonucleotide. FPLC was used to characterize plasma lipoprotein profiles. Plaque area and necrotic core size were quantified and immunohistochemical assessment of lesions using a variety of cellular and protein markers was performed. RESULTS: Male and female Tg(LPA+/0;APOB+/0) and Tg(APOB+/0) mice exhibited proatherogenic lipoprotein profiles with increased cholesterol-rich VLDL and LDL-sized particles and no difference in plasma total cholesterol between genotypes. Complex lesions developed in the aortic sinus of all mice. Plaque area (+22%), necrotic core size (+25%), and calcified area (+65%) were all significantly increased in female Tg(LPA+/0;APOB+/0) mice compared to female Tg(APOB+/0) mice. Immunohistochemistry of lesions demonstrated that apo(a) deposited in a similar pattern as apoB-100 in Tg(LPA+/0;APOB+/0) mice. Furthermore, female Tg(LPA+/0;APOB+/0) mice exhibited less organized collagen deposition as well as 42% higher staining for oxidized phospholipids (OxPL) compared to female Tg(APOB+/0) mice. Tg(LPA+/0;APOB+/0) mice had dramatically higher levels of plasma OxPL-apo(a) and OxPL-apoB compared to Tg(APOB+/0) mice, and female Tg(LPA+/0;APOB+/0) mice had higher plasma levels of the proinflammatory cytokine MCP-1 (+3.1-fold) compared to female Tg(APOB+/0) mice. CONCLUSIONS: These data suggest a pro-inflammatory phenotype exhibited by female Tg mice expressing Lp(a) that appears to contribute to the development of more severe lesions with greater vulnerable features.


Assuntos
Aterosclerose , Lipoproteína(a) , Masculino , Humanos , Feminino , Camundongos , Animais , Lipoproteína(a)/genética , Apolipoproteína B-100/genética , Camundongos Transgênicos , Aterosclerose/genética , Aterosclerose/metabolismo , Apolipoproteínas B , Apolipoproteínas A , Apoproteína(a) , Colesterol
2.
Innovations (Phila) ; 18(2): 196-199, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36872584

RESUMO

Thoracic endovascular aortic repair (TEVAR) explantation remains a challenge due to endovascular graft ingrowth into the aortic wall with time. Surgical access into the aortic arch can be difficult either via sternotomy or thoracotomy, and proximal barbs become engaged firmly into the aortic wall. Explantation often requires extensive thoracic aortic resection, sometimes from the distal aortic arch to the abdominal aorta, followed by reconstruction, risking injury to surrounding neurovascular structures and even death. In cases of blunt thoracic aortic injury, the original injury is often healed, and failed TEVAR could theoretically be removed when thrombotic complications occur. We present a novel technique to facilitate TEVAR recapture with limited distal thoracic aorta replacement.


Assuntos
Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Prótese Vascular , Implante de Prótese Vascular/métodos , Stents , Aneurisma da Aorta Torácica/cirurgia , Aorta Torácica/cirurgia , Procedimentos Endovasculares/métodos , Resultado do Tratamento , Estudos Retrospectivos
3.
Rev Cardiovasc Med ; 24(3): 85, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39077485

RESUMO

Background: The population of adults with congenital heart defects (ACHD) is growing. The leading cause of premature death in these patients is heart failure (HF). However, there is still limited information on the predictive factors for HF in ACHD patients. Objectives: This study re-examined a group of patients with repaired or palliated congenital heart defects (CHD) that were initially studied in 2003. A follow-up period of 15 years has allowed us to identify and evaluate predictors for the development of HF in ACHD. Methods: All patients with repaired or palliated CHD who participated in the initial study (n = 364) were invited for a follow-up examination. The effects of maximum oxygen uptake ( VO 2max ) during exercise stress testing, the cardiac biomarker N-terminal pro brain natriuretic peptide (NT-proBNP), and QRS complex on the development of HF during the follow-up period were investigated. Results: From May 2017 to April 2019, 249 of the initial 364 (68%) patients participated in the follow-up study. Of these, 21% were found to have mild CHD, 60% had moderate CHD, and 19% had complex CHD. Significant predictors for the development of HF were: NT-proBNP level > 1.7 times the upper normal limit, VO 2max < 73% of predicted values, and QRS complex duration > 120 ms. Combination of these three parameters resulted in the highest area-under-the-curve of 0.75, with a sensitivity of 75% and specificity of 63% for predicting the development of HF. Conclusions: In this cohort of ACHD patients, the combination of VO 2max% , NT-proBNP, and QRS duration was predictive of HF development over a 15-year follow-up period. Enhanced surveillance of these parameters in patients with ACHD may be beneficial for the prevention of HF and early intervention.

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