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BACKGROUND: To investigate the association between erectile dysfunction (ED) as well as epistaxis (ES) in relation to the extent of iliac atherosclerosis. METHODS: In this retrospective cross-sectional study, all consecutive male patients treated at our institution from 01/2016 to 12/2020 undergoing abdominal CT scan were evaluated. Patients (n = 1272) were invited by mail to participate in the study in returning two questionnaires for the evaluation of ED (IIEF-5) and ES. Patients who returned filled-in questionnaires within a 3-month deadline were included in the study. The extent of atherosclerosis in the common iliac artery (CIA) and the internal iliac artery (IIA) was assessed by calcium scoring on unenhanced CT. Stratification of results was performed according to reported IIEF-5 scores and consequential ED groups. RESULTS: In total, 437 patients (34.4% of contacted) met the inclusion criteria. Forty-two patients did not fulfill predefined age requirements (< 75 years) and 120 patients had to be excluded as calcium scoring on nonenhanced CT was not feasible. Finally, 275 patients were included in the analysis and stratified into groups of "no-mild" (n = 146) and "moderate-severe" (n = 129) ED. The calcium score (r=-0.28, p < 0.001) and the number of atherosclerotic lesions (r=-0.32, p < 0.001) in the CIA + IIA showed a significant negative correlation to the IIEF-5 score, respectively. Patients differed significantly in CIA + IIA calcium score (difference: 167.4, p < 0.001) and number of atherosclerotic lesions (difference: 5.00, p < 0.001) when belonging to the "no-mild" vs. "moderate-severe" ED group, respectively. A multivariable regression model, after adjusting for relevant baseline characteristics, showed that the number of atherosclerotic CIA + IIA lesions was an independent predictor of ED (OR = 1.05, p = 0.036), whereas CIA + IIA calcium score was not (OR = 1.00031, p = 0.20). No relevant correlation was found between ES episodes and IIEF-5 scores (r=-0.069, p = 0.25), CIA + IIA calcium score (r=-0.10, p = 0.87) or number of atherosclerotic CIA + IIA lesions (r=-0.032, p = 0.60), respectively. CONCLUSIONS: The number of atherosclerotic lesions in the iliac arteries on nonenhanced abdominal CT scans is associated with the severity of ED. This may be used to identify subclinical cardiovascular disease and to quantify the risk for cardiovascular hazards in the future. TRIAL REGISTRATION: BASEC-Nr. 2020 - 01637.
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Aterosclerosis , Disfunción Eréctil , Humanos , Masculino , Anciano , Disfunción Eréctil/diagnóstico por imagen , Disfunción Eréctil/complicaciones , Arteria Ilíaca/diagnóstico por imagen , Estudios Retrospectivos , Calcio , Estudios Transversales , Epistaxis/complicaciones , Aterosclerosis/complicaciones , Aterosclerosis/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Normalization of arterial inflammation inhibits atherosclerosis. The preventive role for protocatechuic acid (PCA) in early-stage atherosclerosis is well recognized; however, its therapeutic role in late-stage atherosclerosis remains unexplored. OBJECTIVE: We investigated whether PCA inhibits vulnerable atherosclerosis progression by normalizing arterial inflammation. METHODS: Thirty-wk-old male apolipoprotein E-deficient (Apoe-/-) mice with vulnerable atherosclerotic lesions in the brachiocephalic artery were fed the AIN-93G diet alone (control) or supplemented with 0.003% PCA (wt:wt) for 20 wk. Lesion size and composition, IL-1ß, and NF-κB in the brachiocephalic arteries, and serum lipid profiles, oxidative status, and proinflammatory cytokines (e.g., IL-1ß, monocyte chemoattractant protein-1, and serum amyloid A) were measured. Moreover, the effect of PCA on the inflammation response was evaluated in efferocytic macrophages from C57BL/6J mice. RESULTS: Compared with the control treatment, dietary PCA supplementation significantly reduced lesion size (27.5%; P < 0.05) and also improved lesion stability (P < 0.05) as evidenced by increased thin fibrous cap thickness (31.7%) and collagen accumulation (58.3%), reduced necrotic core size (37.6%) and cellular apoptosis (73.9%), reduced macrophage accumulation (45.1%), and increased vascular smooth muscle cell accumulation (51.5%). Moreover, PCA supplementation inhibited IL-1ß expression (53.7%) and NF-κB activation (64.4%) in lesions. However, PCA supplementation did not change serum lipid profiles, total antioxidant capacity, and inflammatory cytokines. In efferocytic macrophages, PCA at 0.5 and 1 µmol/L inhibited Il1b/IL-1ß mRNA (27.2-46.5%) and protein (29.2-49.6%) expression and NF-κB activation (67.0-80.3%) by upregulation of MER proto-oncogene tyrosine kinase (MERTK) and inhibition of mitogen-activated protein kinase 3/1 (MAPK3/1). Strikingly, the similar pattern of the MERTK and MAPK3/1 changes in lesional macrophages of mice after PCA intervention in vivo was recapitulated. CONCLUSION: PCA inhibits vulnerable lesion progression in mice, which might partially be caused by normalization of arterial inflammation by upregulation of MERTK and inhibition of MAPK3/1 in lesional macrophages.
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Apolipoproteínas E/deficiencia , Aterosclerosis/patología , Aterosclerosis/prevención & control , Hidroxibenzoatos/administración & dosificación , Animales , Antiinflamatorios , Apolipoproteínas E/genética , Apolipoproteínas E/fisiología , Células Cultivadas , Suplementos Dietéticos , Modelos Animales de Enfermedad , Expresión Génica/efectos de los fármacos , Interleucina-1beta/metabolismo , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 1 Activada por Mitógenos/fisiología , Proteína Quinasa 3 Activada por Mitógenos/antagonistas & inhibidores , FN-kappa B/metabolismo , Tirosina Quinasa c-Mer/genética , Tirosina Quinasa c-Mer/fisiologíaRESUMEN
AIM: The purpose of this study was to investigate the natural course of stenosis of the common carotid artery (CCA) after carotid endarterectomy, as well as the long-term outcomes of various methods of reconstruction of the internal carotid artery (ICA) in patients with extended atherosclerotic lesions. PATIENTS AND METHODS: Presented herein are the remote retrospective and prospective results of carotid endarterectomy in a total of 78 patients with concomitant atherosclerotic lesions of carotid arteries. Depending on the degree of CCA stenosis, the patients were divided into 2 groups. Group One (n=25): stenosis of the internal carotid artery (ICA) of more than 70% and haemodynamically insignificant (30-35% stenosis) but extended (from 3.0 to 5.0 cm (Q1, Me, Q3); 3.5 cm, 4.0 cm, 5.0 cm) stenosis of the CCA. These patients underwent carotid endarterectomy (CEA) from the ostium of the ICA, during which an atherosclerotic plaque was not completely removed from the CCA because the stenosis was extended but haemodynamically insignificant. Group Two (n=53): stenosis of the ICA of more than 70% and haemodynamically significant, extended (from 7.0 to 10.0 cm (Q1, Me, Q3); 7.5 cm, 8.0 cm, 9.0 cm) stenosis of the CCA. The patients of this group were subjected to various methods of operative intervention on the ICA and CCA: carotid endarterectomy (ECA) combined with open endarterectomy from the CCA with plasty using the primary suture (n=23); carotid endarterectomy and alloreconstruction of the CCA (n=10); simultaneous eversion endarterectomy from the ICA and CCA (n=20). The remote period of follow up of patients ranged from 14 to 24 months ((Q1, Me, Q3; 19 months, 22 months, 24 months). The differences were statistically insignificant (Mann-Whitney U-test, p=0.881). RESULTS: In the remote postoperative period, 32% of Group One patients after previously performed carotid endarterectomy were found to have an increase in the degree of stenosis of the CCA up to a haemodynamically significant one (70% and more), thus suggesting progression of the atherosclerotic process. In Group Two patients, after plasty of the CCA with the primary suture, 21.7% of patients were diagnosed as having restenosis of the reconstruction zone up to 30%, with no neurological deficit. 20% of patients after carotid endarterectomy and alloreconstruction of the CCA were diagnosed as having restenosis of the reconstruction zone more than 70% and acute impairment of cerebral circulation with a lethal outcome. The patients after simultaneous eversion endarterectomy form the ICA and CCA in the intraoperative and postoperative periods had neither restenosis of the reconstruction zone nor neurological deficit. CONCLUSION: 32% of patients after previously performed carotid endarterectomy with the presence of extended, but haemodynamically insignificant stenosis of the CCA (30-35% stenosis) in the postoperative period were found to have progression of the atherosclerotic lesion in the form of an increased degree of stenosis up to haemodynamically significant (more than 70%), thus requiring repeat reconstructive operation. Therefore, in patients presenting with concomitant atherosclerotic lesions of the carotid arteries it is appropriate to carry out operative intervention simultaneously on the ICA and CCA, which would make it possible to considerably improve the remote postoperative results of reconstructive interventions on the carotid basin in this cohort of patients. A comparative study of the outcomes of various methods of reconstruction of carotid arteries in patients with concomitant atherosclerotic lesions of the ICA and CCA demonstrated that simultaneous eversion endarterectomy from the ICA and CCA resulted in good postoperative parameters: absence of restenosis and neurological deficit in the remote period of follow up.
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Enfermedades de las Arterias Carótidas/cirugía , Arteria Carótida Común/cirugía , Arteria Carótida Interna/cirugía , Endarterectomía Carotidea/métodos , Arteria Carótida Común/patología , Arteria Carótida Interna/patología , Estenosis Carotídea/cirugía , Progresión de la Enfermedad , Humanos , Estudios Prospectivos , Recurrencia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Mitochondrial genome mutations are associated with different pathologies. Earlier the authors of the study found an association of some mitochondrial genome mutations with atherosclerosis. In the present study, an attempt to analyze a connection of detected mutations with the age of patients with atherosclerosis was made. The investigated sample included 700 individuals, examined by ultrasonography in polyclinics of Moscow and the Moscow region. The sample was divided approximately into two equal parts. The first part included patients with carotid atherosclerosis. The second part included conventionally healthy study participants. In PCR-fragments of individuals' DNA the heteroplasmy level of investigated mutations was quantitatively measured by the method, developed by members of our laboratory on the basis of pyrosequencing technology. According to the obtained results mutations G12315A, G14459A and G15059A were significantly associated with the age of the study participants. The same time one nucleotide replacements A1555G and G14846A correlated negatively with the age at a high level of significance. Thus, in the present study an association of atherogenic mitochondrial genome mutations with age was found. Antiatherogenic mutations were correlated with the age negatively. This prompts a suggestion about common mechanisms of atherogenesis and aging.
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Envejecimiento/genética , Enfermedades de las Arterias Carótidas/genética , ADN Mitocondrial/genética , Factores de Edad , Humanos , Mutación , Reacción en Cadena de la PolimerasaRESUMEN
The fifth subfraction of low-density lipoprotein (L5 LDL) can be separated from human LDL using fast-protein liquid chromatography with an anion exchange column. L5 LDL induces vascular endothelial injury both in vitro and in vivo through the lectin-like oxidized LDL receptor-1 (LOX-1). However, no in vivo evidence shows the tendency of L5 LDL deposition on vascular endothelium and links to dysfunction. This study aimed to investigate L5 LDL retention in vivo using SPECT/CT imaging, with Iodine-131 (131I)-labeled and injected into six-month-old apolipoprotein E knockout (apoE-/-) mice through tail veins. Besides, we examined the biodistribution of L5 LDL in tissues and analyzed the intracellular trafficking in human aortic endothelial cells (HAoECs) by confocal microscopy. The impacts of L5 LDL on HAoECs were analyzed using electron microscopy for mitochondrial morphology and western blotting for signaling. Results showed 131I-labeled-L5 was preferentially deposited in the heart and vessels compared to L1 LDL. Furthermore, L5 LDL was co-localized with the mitochondria and associated with mitofusin (MFN1/2) and optic atrophy protein 1 (OPA1) downregulation, leading to mitochondrial fission. In summary, L5 LDL exhibits a propensity for subendothelial retention, thereby promoting endothelial dysfunction and the formation of atherosclerotic lesions.
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BACKGROUND AND AIMS: We tested the hypothesis that on-treatment HbA1c levels independently associate with coronary atheroma progression and major adverse cardiovascular events (MACE: death, myocardial infarction, cerebrovascular accident, coronary revascularization, or hospitalization for unstable angina) rates. METHODS: We performed a post-hoc pooled analysis of data from seven prospective, randomized trials involving serial coronary intravascular ultrasonography (IVUS). The percent atheroma volume (PAV) was calculated as the proportion of the entire vessel wall occupied by atherosclerotic plaque. Using multivariable mixed modeling, we determined the association of on-treatment HbA1c with annualized change in PAV. Cox proportional hazard models were used to assess the association of HbA1c with incidence of MACE. RESULTS: Among 3,312 patients (mean age 58.6±9years, 28.4%women) average on-treatment HbA1c was 6.2±1.1%. Overall, there was no net significant annualized change in PAV (0.12±0.19%, p = 0.52). In a fully adjusted multivariable analysis (following adjustment of age, sex, body mass index, systolic blood pressure, smoking, low- and high-density lipoprotein cholesterol, triglyceride levels, peripheral vascular disease, trial, region, and baseline PAV), higher on-treatment HbA1c levels were independently associated with annualized changes in PAV [beta-estimate (95% confidence interval): 0.13(0.08, 0.19), p < 0.001]. On-treatment HbA1c levels were independently associated with MACE [hazard ratio (95% confidence interval): 1.13(1.04, 1.23), p = 0.005]. CONCLUSIONS: Independent of achieved cardiovascular risk factor control, greater HbA1c levels significantly associate with coronary atheroma progression rates and clinical outcomes. These results support the notion of a direct, specific effect of glycemic control upon coronary atheroma and atherosclerotic events, supporting the rationale of therapies designed to directly modulate it.
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Gycyrrhizic acid (GA), an inhibitor of high mobility group box 1 (HMGB1), inhibits inflammatory responses and is involved in the occurrence and development of several inflammationrelated diseases. However, the role of GA in the atherosclerotic lesions caused by diabetes mellitus (DM) remains unknown. In the present study, Sprague Dawley rats were selected to desi=gn a diabetic atherosclerosis (AS) model. Rats from the DMAS group were subsequently divided into DMAS, DMAS + GA (50 mg/kg) and DMAS + GA (150 mg/kg) groups. Biochemical analyzers were used to measure levels of blood glucose, fasting insulin, total cholesterol, total triglyceride, lowdensity lipoprotein and highdensity lipoprotein. The number of plaques was recorded after collection of thoracic aortas from the rats. The intimal thickness of arterial tissue was detected by hematoxylin and eosin staining. The expression levels of CD68 and αsmooth muscle actin (αSMA) were detected by immunohistochemistry. The expression of tumor necrosis factorα, interleukin (IL)6 and IL1ß in the serum of the rats was detected by ELISA. The expression of fatty acid synthetase, sterol regulatory element binding protein 1C, HMGB1 and receptor for advanced glycation end products (RAGE) was detected by western blotting. Reverse transcription quantitative PCR was used to detect the mRNA expression of HMGB1 and RAGE. The results demonstrated that GA treatment could decrease the body weight, blood glucose level and biochemical parameters of AS DM rats in a dosedependent manner. In addition, GA decreased the intimal thickness of carotid artery and the formation of plaque in rats with diabetic AS. Furthermore, GA inhibited macrophage activation and decreased αSMA expression in vascular smooth muscle cells, and decreased the expression of proteins (FAS and SREBP1c) and inflammatory factors. Taken together, the findings from the present study demonstrated that GA may have a therapeutic effect on DMassociated AS. This study provides a theoretical basis for the treatment of diabetic AS.
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Aterosclerosis/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Ácido Glicirrínico/farmacología , Proteína HMGB1/antagonistas & inhibidores , Animales , Aterosclerosis/etiología , Diabetes Mellitus Experimental/inducido químicamente , Ácido Glicirrínico/uso terapéutico , Proteína HMGB1/metabolismo , Humanos , Activación de Macrófagos/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Estreptozocina/administración & dosificación , Estreptozocina/toxicidadRESUMEN
OBJECTIVE: An increased ω6/ω3-polyunsaturated fatty acid ratio in the current Western diet is regarded as a critical epigenetic nutritional factor in the pathogenesis of several human lifestyle diseases, metabolic syndrome, cardiovascular disease, the central nervous system and the female and male reproductive systems. The impact of nutrient ω3-and ω6-PUFAs in the pathogenesis of dyslipoproteinemia and atherosclerosis has been a topic of intense efforts for several decades. Cellular homeostasis of the ω3-and ω6- PUFA pool is maintained by the synthesis of ω3-and ω6-PUFAs from essential fatty acids (EFA) (linoleic and α-linolenic acid) and their dietary supply. In this study, we used the auxotrophic Δ6-fatty acid desaturase- (FADS2) deficient mouse (fads2-/-), an unbiased model congenial for stringent feeding experiments, to investigate the molecular basis of the proposed protective role of dietary ω3-and ω6-PUFAs (Western diet) in the pathogenesis of multifactorial dyslipoproteinemia and atherosclerosis. We focused on the metabolic axis-liver endoplasmic reticulum (ER), serum lipoprotein system (Lp) and aorta vessel wall. Furthermore, we addressed the impact of the inactivated fads2-locus with inactivated PUFA synthesis on the development and progression of extended atherosclerosis in two different mouse mutants with disrupted cholesterol homeostasis, using the apoe-/- and ldlr-/- mutants and the fads2-/- x apoe-/- and fads2-/- x ldlr-/- double mutants. METHODS: Cohorts of +/+ and fads2-/- mice underwent two long-term dietary regimens: a) a PUFA-free standard chow diet containing only EFAs, essential for viability, and b) a high fat/high cholesterol (HFHC) diet, a mimicry of the human atherogenic "Western" diet. c) To study the molecular impact of PUFA synthesis deficiency on the development and progression of atherosclerosis in the hypercholesterolemic apoe-/- and ldlr-/- mouse models fed PUFA-free regular and sustained HFHC diets, we generated the fads2-/- x apoe-/- and the fads2-/- x ldlr-/- double knockout mutants. We assessed essential molecular, biochemical and cell biological links between the diet-induced modified lipidomes of the membrane systems of the endoplasmic reticulum/Golgi complex, the site of lipid synthesis, the PL monolayer and neutral lipid core of LD and serum-Lp profiles and cellular reactions in the aortic wall. RESULTS: ω3-and ω6-PUFA synthesis deficiency in the fads2-/- mouse causes a) hypocholesterolemia and hypotriglyceridemia, b) dyslipoproteinemia with a shift of high-density lipoprotein (HDL) to very low-density lipoprotein (VLDL)-enriched Lp-pattern and c) altered liver lipid droplet structures. d) Long-term HFHC diet does not trigger atherosclerotic plaque formation in the aortic arc, the thoracic and abdominal aorta of PUFA-deficient fads2-/- mice. Inactivation of the fads2-/- locus, abolishing systemic PUFA synthesis in the fads2-/- x apoe-/- and fads2-/- x ldlr-/- double knockout mouse lines. CONCLUSIONS: Deficiency of ω3-and ω6-PUFA in the fads2-/- mutant perturbs liver lipid metabolism, causes hypocholesterolemia and hypotriglyceridemia and renders the fads2-/- mutant resistant to sustained atherogenic HFHC diet. Neither PUFA-free regular nor long-term HFHC-diet impacts the apoe- and LDL-receptor deficiency-provoked hypercholesterolemia and atherosclerotic plaque formation, size and distribution in the aorta. Our study strongly suggests that the absence of PUFAs as highly vulnerable chemical targets of autoxidation attenuates inflammatory responses and the formation of atherosclerotic lesions. The cumulative data and insight into the molecular basis of the pleiotropic functions of PUFAs challenge a differentiated view of PUFAs as culprits or benefactors during a lifespan, pivotal for legitimate dietary recommendations.
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Aterosclerosis/metabolismo , Ácido Graso Desaturasas/metabolismo , Ácidos Grasos Omega-3/biosíntesis , Ácidos Grasos Omega-6/biosíntesis , Receptores de LDL/metabolismo , Animales , Colesterol en la Dieta/efectos adversos , Dieta Alta en Grasa/efectos adversos , Ácido Graso Desaturasas/deficiencia , Ácido Graso Desaturasas/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de LDL/deficienciaRESUMEN
BACKGROUND: The associations between serum free triiodothyronine (FT3) and diabetic peripheral neuropatprohy (DPN)/carotid atherosclerotic lesions in euthyroid patients with type 2 diabetes are still unclear. The purpose of our study was to explore the relations of FT3 to DPN and carotid atherosclerotic lesions in Chinese type 2 diabetes inpatients with euthyroid function. METHODS: 2477 euthyroid inpatients with type 2 diabetes were recruited and they were stratified into quartiles by FT3 levels in this cross-sectional study. Peripheral neuropathy was assessed by neurological symptoms and signs as well as nerve conduction velocity tests. Carotid atherosclerotic lesions, including carotid intima-media thickness, plaque and stenosis, were evaluated by Doppler ultrasound. RESULTS: The prevalence of DPN in type 2 diabetic patients exhibited the significant decrease across the FT3 quartiles (23.5%, 20.9%, 18.8%, and 11.2%, respectively, p < 0.001). Multiple logistical regression analysis also revealed that FT3 quartiles were significantly and inversely associated with DPN. Compared with the subjects in the highest FT3 quartile, the adjusted odds ratios (95% confidence interval) of DPN from the first to third FT3 quartile were successively 2.338 (1.407-3.884), 1.903 (1.134-3.194) and 1.598 (0.960-1.125). The patients with DPN had significantly higher prevalence of carotid atherosclerotic lesions compared with non-DPN patients. However, no statistical association was observed between FT3 quartiles and carotid atherosclerotic lesions after adjusting for confounder factors. CONCLUSIONS: Lower FT3 within the normal range was independently associated with DPN, but not with carotid atherosclerotic lesions in Chinese euthyroid inpatients with type 2 diabetes.
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AIM: Ischemic stroke (IS) is multifactorial disease and therefore different genes and proteins play a role in its development. Haptoglobin (Hp) removes free hemoglobin and protects from iron-induced oxidative damage, inflammatory response, atherosclerosis and cerebrovascular diseases. The aim of this study was to investigate Hp genetic variants in patients with carotid atherosclerotic lesions and IS. MATERIAL AND METHODS: A total of 121 subjects with IS participated in the study, 81 male and 40 female. RESULTS: Among 121 patients with IS, 79 had diffuse atherosclerotic plaques and stenosis. Hp genotype was statistically significantly associated with CDFI neck carotid artery stenosis findings (p = 0.006). Patients with Hp1-2 genotype had statistically significantly larger odds for atherosclerotic changes compared to those with Hp1-1 genotype, as well as those with Hp2-2 genotype. CONCLUSION: This study has shown an association of the Hp2-2 genotype and atherosclerosis in patients with IS, indicating Hp2-2 genotype as a genetic biomarker for precision medicine and personalized healthcare.
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Aterosclerosis/genética , Isquemia Encefálica/genética , Haptoglobinas/genética , Estenosis Carotídea/genética , Femenino , Genotipo , Haptoglobinas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Placa Aterosclerótica/genética , Polimorfismo Genético/genética , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/genéticaRESUMEN
C-X-C motif chemokine receptor 4 (CXCR4) is expressed on the surface of various cell types involved in atherosclerosis, with a particularly rich receptor expression on macrophages and T cells. First pilot studies with 68Ga-pentixafor, a novel CXCR4-directed PET tracer, have shown promise to noninvasively image inflammation within atherosclerotic plaques. The aim of this retrospective study was to investigate the performance of 68Ga-pentixafor PET/CT for imaging atherosclerosis in comparison to 18F-FDG PET/CT. Methods: Ninety-two patients (37 women and 55 men; mean age, 62 ± 10 y) underwent 68Ga-pentixafor and 18F-FDG PET/CT for staging of oncologic diseases. In these subjects, lesions in the walls of large arteries were identified using morphologic and PET criteria for atherosclerosis (n = 652). Tracer uptake was measured and adjusted for vascular lumen (background) signal by calculation of target-to-background ratios (TBRs) by 2 investigators masked to the other PET scan. On a lesion-to-lesion and patient basis, the TBRs of both PET tracers were compared and additionally correlated to the degree of arterial calcification as quantified in CT. Results: On a lesion-to-lesion basis, 68Ga-pentixafor and 18F-FDG uptake showed a weak correlation (r = 0.28; P < 0.01). 68Ga-pentixafor PET identified more lesions (n = 290; TBR ≥ 1.6, P < 0.01) and demonstrated higher uptake than 18F-FDG PET (1.8 ± 0.5 vs. 1.4 ± 0.4; P < 0.01). The degree of plaque calcification correlated negatively with both 68Ga-pentixafor and 18F-FDG uptake (r = -0.38 vs. -0.31, both P < 0.00001). Conclusion: CXCR4-directed imaging of the arterial wall with 68Ga-pentixafor PET/CT identified more lesions than 18F-FDG PET/CT, with only a weak correlation between tracers. Further studies to elucidate the underlying biologic mechanisms and sources of CXCR4 positivity, and to investigate the clinical utility of chemokine receptor-directed imaging of atherosclerosis, are highly warranted.
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Aterosclerosis/diagnóstico por imagen , Complejos de Coordinación , Fluorodesoxiglucosa F18 , Péptidos Cíclicos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Receptores CXCR4/metabolismo , Aterosclerosis/metabolismo , Transporte Biológico , Femenino , Fluorodesoxiglucosa F18/metabolismo , Humanos , Inflamación/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
PURPOSE: In patients with suspected coronary artery disease (CAD), coexisting extracardiac abnormalities have a major impact on the patient management. This study aimed to evaluate the image quality of whole-body computed tomography (CT) immediately after the coronary computed tomography angiography (CTA) and investigate the incidence of extracardiac findings in patients with suspected CAD. MATERIALS AND METHODS: We enrolled 450 patients undergoing whole-body CT at 100 kVp and model-based iterative reconstruction immediately after the coronary CTA (Group A) and retrospectively reviewed 144 control patients who underwent conventional contrast-enhanced CT (120 kVp) with filtered back projection (Group B). We compared the signal-to-noise ratio (SNR) of the aorta and liver and radiation dose between the two groups. Then, we evaluated the prevalence of extracardiac findings in Group A. RESULTS: Compared with Group B, Group A demonstrated significantly higher aorta and liver SNR and lower radiation dose. In Group A, whole-body CT revealed 229 coexisting lesions in 165 patients, including 32 and 106 cases of oncologic and vascular diseases, respectively. CONCLUSION: Additional whole-body CT after coronary CTA may provide adequate image quality. Using additional whole-body CT, 36% of patients with suspected CAD had clinically relevant coexisting findings, including malignancy.
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Angiografía por Tomografía Computarizada/métodos , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Dosis de Radiación , Imagen de Cuerpo Entero/métodos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Relación Señal-Ruido , Tomografía Computarizada por Rayos X/métodosRESUMEN
OBJECTIVE: The present investigation is concerned with hybrid mediated blood flow model through atherosclerotic bifurcated artery with slip effects by considering the properties of compliant walls. DESIGN/APPROACH: In human body, the circulatory system is made up of a network of blood vessels that include the bifurcation therefore the influence of hybrid nanoparticles on parent artery with mild stenosis, at apex and in the region of daughter arteries (after being bifurcated) is observed. Blood streaming along the segment of vessel is considered to be Newtonian. The compliant nature of the atherosclerotic artery wall is also considered to create association with permeability aspects for the thickness of arterial wall. Property of heat transfer with convective impacts is taken into account to weaken the stenotic lesions. Through phase flow model approach, a mathematical model is develop with the phenomena of hybrid nanofluid. FINDINGS: For theoretical research of designed equations experimentally determined values of nanoparticles and base fluid are used. Further, flow configurations of hemodynamics are figure out to analyze the blood flow through bifurcated stenotic artery. The comparison in parent and daughter artery is plotted for velocity profile. These patterns provide us a graphical way to recognize the importance of theoretical assistance of this model to biomedical field. At the end, it is concluded from graphical results that slip to the boundary reduces the resistance to flow for atherosclerotic bifurcated artery. CONCLUSIONS: In bifurcated artery, blood circulation is assumed due to difference of pressure between atherosclerotic and non-atherosclerotic portions. Slip impacts are more effective to reduce the hemodynamics effects of stenosis for bifurcated artery. Bifurcation angle reduces the shear stress for daughter artery whereas opposite behavior is observed for parent artery. Compliant wall parameters reduces the inner bolus size in stenotic region while number of bolus increases in bifurcated region. Reduction in the amplitude of shear stress for convective parameter is more prominent in the parent artery as compared to daughter artery.
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Aterosclerosis/fisiopatología , Modelos Cardiovasculares , Arterias/patología , Arterias/fisiopatología , Aterosclerosis/patología , Velocidad del Flujo Sanguíneo/fisiología , Adaptabilidad/fisiología , Simulación por Computador , Hemodinámica , Humanos , Conceptos Matemáticos , NanopartículasRESUMEN
Purpose The objective of the study was to evaluate the frequency and severity of atherosclerotic lesions in extracranial sections of carotid arteries and to determine the level of the correlation between these lesions and symptoms of cerebral ischemia. Secondly, to identify the most common risk factors of ischaemic stroke occurrence in population of patients of vascular outpatient clinic. Material and Methods Prospective study was conducted on a group of 1,000 people (217 women and 783 men), aged 50 to 86 years, the average age was 62 years (± 9.95). Results Atherosclerotic lesions of carotid arteries were observed in 670 examined people (67%). In 63 cases (6.3%) carotid artery occlusion was revealed. Patients with symptomatic carotid artery stenosis more frequently were addicted to cigarettes and suffered from hypertension in comparison to asymptomatic group. A statistically significant correlation between the TIA or ischemic stroke and smoking were noticed, as well as between TIA/ischemic stroke and hypertension Conclusions Among patients with atherosclerosis of peripheral arteries atherosclerotic lesions in the extracranial carotid sections occur with a high frequency. Statistically significant differences in the incidence and severity of atherosclerotic lesions in the carotid arteries were observed in this group. A statistically significant correlation was revealed between the prevalence and severity of atherosclerosis in the carotid arteries in symptomatic patients and smoking and hypertension. Performing screening in patients with atherosclerosis of the abdominal aorta and/or lower limb arteries may detect significant carotid artery stenosis, requiring surgical intervention.
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Arteriopatías Oclusivas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Arteria Carótida Interna/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Arteriopatías Oclusivas/patología , Enfermedades de las Arterias Carótidas/patología , Arteria Carótida Interna/patología , Estenosis Carotídea/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Accidente Cerebrovascular/etiología , Ultrasonografía Doppler DúplexRESUMEN
Supra-aortic atherosclerotic lesions, including innominate artery atheromas, are an uncommon but established cause of transient ischemic attacks, stroke, upper extremity ischemia, and vertebrobasilar insufficiency. We present a patient with a transient ischemic attack admitted with right hemispheric symptoms who was found to have a severe ulcerated innominate artery atheroma. The patient underwent an aortic arch angiogram with stenting of the innominate artery. The proper diagnosis, treatment, and management of innominate artery atheromas are imperative to prevent further cardiovascular morbidity and mortality in patients. Currently, both endovascular and surgical options are available for revascularization, and there have been no randomized controlled trials comparing endovascular versus open repair to standardize one as the standard of care over the other. No randomized controlled trials are examining the benefit of dual versus single antiplatelet therapy post-stenting in supra-aortic atherosclerotic lesions. We believe that this topic warrants further research and needs evidence-based guidelines to help direct physicians about treatment and management.
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BACKGROUND AND AIMS: The relation of lipoprotein (a) [Lp(a)] and proprotein convertase substilisin/kexin type 9 (PCSK9) levels to coronary artery disease (CAD) has been well established in the general population, while little is known about the association between Lp(a) or PCSK9 and atherosclerotic lesions of different artery sites in patients with familial hypercholesterolemia (FH). METHODS: One hundred and fifty-one patients with verified genotyped heterozygous FH (HeFH) were enrolled. There were available data regarding coronary angiography and carotid ultrasonography in 151 patients and femoral ultrasonography in 55 patients. Coronary and carotid severity was evaluated by Gensini score and Crouse score. PCSK9 and Lp(a) concentrations were determined by ELISA and immunoturbidimetry, respectively. Finally, the correlation of PCSK9 and Lp(a) with the presence and severity of CAD and peripheral artery disease (PAD) was assessed. RESULTS: The distributions of PCSK9 and Lp(a) were skewed and a close correlation between them in HeFH patients was found. PCSK9 levels were significantly higher in patients with coronary and carotid atherosclerotic lesions compared to their non-atherosclerotic groups, while no difference was found in femoral atherosclerotic lesions groups. Lp(a) levels only differed between patients with or without coronary atherosclerotic lesions. Patients with highest PCSK9 and Lp(a) concentrations had the highest prevalence and severity of atherosclerotic lesions. Multivariate regression analysis showed that PCSK9 was independently associated with CAD and PAD, while Lp(a) was only associated with CAD. CONCLUSIONS: Circulating PCSK9 concentrations were associated with an increased risk of CAD and PAD, while Lp(a) was only a marker for CAD in HeFH patients.
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Enfermedades de las Arterias Carótidas/sangre , Enfermedad de la Arteria Coronaria/sangre , Hiperlipoproteinemia Tipo II/sangre , Lipoproteína(a)/sangre , Enfermedad Arterial Periférica/sangre , Proproteína Convertasa 9/sangre , Adulto , Biomarcadores/sangre , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/genética , Grosor Intima-Media Carotídeo , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/genética , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Predisposición Genética a la Enfermedad , Heterocigoto , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/genética , Fenotipo , Placa Aterosclerótica , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
Objective: To assess the use of a nitinol stent to treat symptomatic stenoses or occlusions of the native superficial femoral artery (SFA). Materials and Methods: Seventy-four patients were treated at 12 Japanese sites. The primary endpoint, freedom from target-limb failure (TLF), was a composite of device- or procedure-related death, target-limb amputation, target-vessel revascularization (TVR), or restenosis compared to an objective performance goal (OPG) at 12 months. Secondary endpoints, including primary patency, freedom from TVR/target-lesion revascularization (TLR), improvements in clinical parameters, and major adverse events (MAEs) were evaluated through 36 months. Results: The mean overall lesion length was 80.7±38.9 mm (mean stented length: 98.8±46.1 mm). Freedom from TLF was 81.2% (p<0.001 compared to OPG) with a Kaplan-Meier estimate of 84.2% [95% confidence interval (95%CI) 73.3%, 90.9%] at 12 months. Primary patency was 71.0% at 12 months and 67.8% at 36 months. A total of 94.7% of patients improved by at least one Rutherford category and 70.2% of patients improved ankle-brachial indices â§0.10 from baseline to 36 months. Freedom from TVR/TLR (Kaplan-Meier) was 90% at 12 months and 79.5% at 36 months. Four MAEs were reported; none were found to be device or procedure related. Conclusion: A self-expanding stent was used safely to treat stenotic and occlusive lesions of the SFA in a Japanese patient population. The composite endpoint, freedom from TLF, was superior to an historical control at one year, with low rates of revascularization and good functional and clinical outcomes through three years.
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Accumulating evidence has suggested that intake of whole grains is a protective factor against pathogenesis of coronary artery disease. The exact mechanisms, however, are still not clearly understood. In this study, we hypothesized that adequate intake of corn fractions (aleurone, endosperm and germ) can modify lipid profiles in relation to atherosclerotic lesion development in low-density lipoprotein receptor knockout (LDLr-KO) mice. The purpose of the present study was to investigate the potential cardiovascular benefits of corn fractions in LDLr-KO mice through a number of biomarkers including lipid profile, and morphologic and morphometrical analysis of atherosclerotic lesions in aortic root. Four groups of male LDLr-KO mice were fed with the experimental diets supplemented with (3 treated) or without (control) 5% (wt/wt) of each of corn fractions for 10 weeks. All diets were supplemented with 0.06% (wt/wt) cholesterol. Compared with mice in the control group, atherosclerotic lesions in the aortic roots were significantly reduced (P=.003) in the mice that were fed diet supplemented with aleurone and germ fractions. This effect was associated with significant reductions in plasma total (P=.02) and LDL (P=.03) cholesterol levels, and an increase in fecal cholesterol excretion (P=.04). Furthermore, abdominal fat mass was significantly reduced by consumption of aleurone (P=.03). In summary, the consumption of aleurone and germ may help attenuate atherosclerosis by reducing plasma total and LDL cholesterol levels.
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Aterosclerosis/dietoterapia , Dieta , Grano Comestible , Lipoproteínas LDL/sangre , Preparaciones de Plantas/uso terapéutico , Receptores de LDL/sangre , Zea mays , Grasa Abdominal/metabolismo , Animales , Aorta/efectos de los fármacos , Aorta/patología , Aterosclerosis/sangre , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/patología , Biomarcadores/sangre , Colesterol en la Dieta , Fibras de la Dieta , Suplementos Dietéticos , Endospermo , Heces/química , Masculino , Ratones , Ratones Noqueados , Preparaciones de Plantas/farmacología , Proteínas de Plantas , Estructuras de las Plantas , Placa Aterosclerótica/prevención & controlRESUMEN
BACKGROUND: Apoe-deficient (Apoe-/-) mice develop progressive atherosclerotic lesions with age but no severe renal pathology in the absence of additional challenges. We recently described accelerated atherosclerosis as well as marked renal injury in Apoe-/- mice deficient in the mesenchymal integrin chain Itga8 (Itga8-/-). Here, we used this Apoe-/-, Itga8-/- mouse model to investigate the sex differences in the development of atherosclerosis and concomitant renal injury. We hypothesized that aging female mice are protected from vascular and renal damage in this mouse model. METHODS: Apoe-/- mice were backcrossed with Itga8-/- mice. Mice were kept on a normal diet. At the age of 12 months, the aortae and kidneys of male and female Apoe-/-Itga8+/+ mice or Apoe-/-Itga8-/- mice were studied. En face preparations of the aorta were stained with Sudan IV (lipid deposition) or von Kossa (calcification). In kidney tissue, immunostaining for collagen IV, CD3, F4/80, and PCNA and real-time PCR analyses for Il6, Vegfa, Col1a1 (collagen I), and Ssp1 (secreted phosphoprotein 1, synonym osteopontin) as well as ER stress markers were performed. RESULTS: When compared to male mice, Apoe-/-Itga8+/+ female mice had a lower body weight, equal serum cholesterol levels, and lower triglyceride levels. However, female mice had increased aortic lipid deposition and more aortic calcifications than males. Male Apoe-/- mice with the additional deficiency of Itga8 developed increased serum urea, glomerulosclerosis, renal immune cell infiltration, and reduced glomerular cell proliferation. In females of the same genotype, these renal changes were less pronounced and were accompanied by lower expression of interleukin-6 and collagen I, while osteopontin expression was higher and markers of ER stress were not different. CONCLUSIONS: In this model of atherosclerosis, the female sex is a risk factor to develop more severe atherosclerotic lesions, even though serum fat levels are higher in males. In contrast, female mice are protected from renal damage, which is accompanied by attenuated inflammation and matrix deposition. Thus, sex affects vascular and renal injury in a differential manner.
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Apolipoproteínas E/genética , Aterosclerosis/patología , Aterosclerosis/fisiopatología , Cadenas alfa de Integrinas/genética , Riñón/patología , Caracteres Sexuales , Animales , Aorta Torácica/patología , Aterosclerosis/genética , Aterosclerosis/metabolismo , Modelos Animales de Enfermedad , Estrés del Retículo Endoplásmico , Femenino , Inflamación/fisiopatología , Riñón/metabolismo , Riñón/fisiopatología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados para ApoE , ARN Mensajero/metabolismoRESUMEN
The primary aim of our current study was to utilize hyaluronic acid (HA) to decorate reconstituted high density lipoprotein (rHDL) loaded with lovastatin (LT), termed as HA-LT-rHDL, in order to investigate whether coating HA could efficiently evade from the undesired uptake of LT-rHDL in liver mediated by scavenger receptor class B type I (SR-BI) and then greatly accumulate LT-rHDL in atherosclerotic lesions via strong HA affinity to CD44 up-regulated at inflammatory sites such as atherosclerotic lesions, thus exerting enhanced atheroprotective efficacy. In vitro characterizations indicated the successful HA decoration onto the surface of LT-rHDL, which could be indirectly verified by the increased particle size, enhanced negative surface charge and reduced in vitro drug release rate after HA decoration. Compared with rHDL without HA, HA decoration endowed rHDL with better atherosclerotic lesions targeting efficiency and lower liver accumulation, proved by results from ex vivo imaging and tissue distribution. Furthermore, atheroprotective efficacy in model animal showed that HA-LT-rHDL had the best potent efficacy than other LT preparations, which was demonstrated by the fewest atherosclerotic lesions sizes, the most minimum mean intima-media thickness (MIT), the lowest macrophage infiltration and expression of matrix metalloproteinase-9 (MMP-9), respectively. Above results demonstrated that the newly designed HA-LT-rHDL could decrease the non-targeted uptake by liver and deliver a large amount of drug into atherosclerotic lesions so as to efficiently suppress the advancement of atherosclerosis.