RESUMEN
Hypertension is a risk factor for cardiovascular diseases such as coronary artery disease, heart failure, and stroke. Lignosus rhinocerus (Cooke) Ryvarden (also known as tiger milk mushroom), has been reported to exhibit a range of pharmacological effects, such as anti-inflammatory, anti-proliferative, antioxidative, immunomodulatory and anti-asthmatic activities. Thus far, there is limited research that has explored its ability to mediate vascular effects in vivo. Therefore, this study investigated the antihypertensive and vascular protective effects of L. rhinocerus TM02® sclerotia supplementation in spontaneously hypertensive rats (SHR). Wistar Kyoto (WKY) rats served as a normotensive control group. SHR were orally administered with L. rhinocerus TM02® sclerotia (100 mg/kg and 300 mg/kg, respectively) for 8 weeks, and blood pressure was monitored every 2 weeks. Vascular function was evaluated using an organ bath (aorta) and wire myograph (renal artery) at the treatment endpoint. The levels of reactive oxygen species (ROS) and nitric oxide (NO) in the aorta and renal artery were evaluated using dihydroethidium (DHE) and difluoro fluorescein acetate (DAF-FM) fluorescence assays, respectively. Total plasma nitrate/nitrite and tumor necrosis factor alpha (TNF-α) levels were evaluated via colorimetric assays. In vivo treatment with L. rhinocerus TM02® sclerotia significantly attenuated the increase in systolic blood pressure (SBP). It also alleviated vascular dysfunction and decreased elevated ROS in the aorta and renal arteries of the treated SHRs. Moreover, L. rhinocerus TM02® sclerotia attenuated plasma TNF-α level but increased total plasma nitrate/nitrite, albeit slightly, coupled with significantly increased NO at the vascular level. Collectively, the present study demonstrated that L. rhinocerus TM02® sclerotia supplementation exerted blood pressure lowering effects, partly attributed to improvements in vascular function via reduction in vascular oxidative stress.
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Presión Sanguínea , Hipertensión , Estrés Oxidativo , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Animales , Estrés Oxidativo/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Ratas , Masculino , Presión Sanguínea/efectos de los fármacos , Óxido Nítrico/metabolismo , Óxido Nítrico/sangre , Antihipertensivos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Suplementos Dietéticos , Aorta/efectos de los fármacos , Aorta/fisiopatologíaRESUMEN
BACKGROUND: As the pulmonary system and cardiovascular system are intimately linked, patients with chronic obstructive pulmonary disease (COPD) and asthma have high risk for developing cardiovascular diseases (CVDs) and altered central hemodynamic. OBJECTIVE: We aim to assess the central aortic blood pressure (CABP) indices, pulse wave velocity (PWV) and other indicators of arterial stiffness in Indian patients with COPD and bronchial asthma. METHODS: This is a single-center, cross-sectional study conducted in outpatients diagnosed with either chronic stable phase of COPD or bronchial asthma. CABP indices, vascular age, arterial stiffness and central hemodynamics were measured in patients. RESULTS: Of 193 patients with obstructive airway disease who were enrolled, (n = 81 had COPD and n = 112 had partially-controlled bronchial asthma) the proportion of male patients was higher in both groups. The PWV, augmentation index (AI) and vascular age (VA) were significantly higher in patients with COPD compared to those with bronchial asthma (all, p < 0.05). CONCLUSION: The study showed that PWV, AI and VA were higher in patients with stable COPD without any cardiac comorbidities compared to bronchial asthma.
Asunto(s)
Asma , Enfermedad Pulmonar Obstructiva Crónica , Análisis de la Onda del Pulso , Rigidez Vascular , Humanos , Masculino , Rigidez Vascular/fisiología , Femenino , Persona de Mediana Edad , Asma/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Anciano , Estudios Transversales , Adulto , Presión Arterial/fisiología , Aorta/fisiopatología , Presión Sanguínea/fisiologíaRESUMEN
BACKGROUND AND OBJECTIVE: The evidence on the role of hemodynamics in aorta pathophysiology has yet to be robustly translated into clinical applications, to improve risk stratification of aortic diseases. Motivated by the need to enrich the current understanding of the pathophysiology of the ascending aorta (AAo), this study evaluates in vivo how large-scale aortic flow coherence is affected by AAo dilation and aortic valve phenotype. METHODS: A complex networks-based approach is applied to 4D flow MRI data to quantify subject-specific AAo flow coherence in terms of correlation between axial velocity waveforms and the aortic flow rate waveform along the cardiac cycle. The anatomical length of persistence of such correlation is quantified using the recently proposed network metric average weighted curvilinear distance (AWCD). The analysis considers 107 subjects selected to allow an ample stratification in terms of aortic valve morphology, absence/presence of AAo dilation and of aortic valve stenosis. RESULTS: The analysis highlights that the presence of AAo dilation as well as of bicuspid aortic valve phenotype breaks the physiological AAo flow coherence, quantified in terms of AWCD. Of notice, it emerges that cycle-average blood flow rate and relative AAo dilation are main determinants of AWCD, playing opposite roles in promoting and hampering the persistence of large-scale flow coherence in AAo, respectively. CONCLUSIONS: The findings of this study can contribute to broaden the current mechanistic link between large-scale blood flow coherence and aortic pathophysiology, with the prospect of enriching the existing tools for the in vivo non-invasive hemodynamic risk assessment for aortic diseases onset and progression.
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Aorta , Válvula Aórtica , Imagen por Resonancia Magnética , Fenotipo , Humanos , Aorta/diagnóstico por imagen , Aorta/fisiopatología , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/fisiopatología , Imagen por Resonancia Magnética/métodos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Hemodinámica , Velocidad del Flujo Sanguíneo , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/fisiopatología , Anciano , Enfermedad de la Válvula Aórtica Bicúspide/fisiopatología , Enfermedad de la Válvula Aórtica Bicúspide/diagnóstico por imagenRESUMEN
PURPOSE: Cardiogenic shock still has a high mortality. In order to correctly manage these patients, it is useful to have available haemodynamic parameters, invasive and non-invasive. The aim of this review is to show the current evidence on the use of echocardiographic aortic flow assessment by left ventricular outflow tract - velocity time integral. METHODS: Publications relevant to the discussion of echocardiographic aortic flow assessment by left ventricular outflow tract - velocity time integral and cardiogenic shock, were retrieved from PubMed®. RESULTS: Left ventricular outflow tract - velocity time integral is an easily sampled and reproducible parameter that has already been shown to have prognostic value in various cardiovascular pathologies, including myocardial infarction and heart failure. Although there are still few data available in the literature, the LVOT-VTI also seems to have an important role in CS from prognosis to guidance in the escalation/de-escalation of vasoactive therapy and to support devices by allowing an estimate of patient's probability of response to fluid administration. CONCLUSION: Aortic flow assessment can become a very useful invasive parameter in the management of cardiogenic shock.
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Ecocardiografía Doppler , Choque Cardiogénico , Humanos , Choque Cardiogénico/fisiopatología , Choque Cardiogénico/diagnóstico por imagen , Ecocardiografía Doppler/métodos , Velocidad del Flujo Sanguíneo/fisiología , Aorta/diagnóstico por imagen , Aorta/fisiopatología , PronósticoRESUMEN
BACKGROUND: Aortic conduit and reservoir functions can be directly measured by four-dimensional flow (4D flow) cardiovascular magnetic resonance (CMR). METHODS: Twenty healthy controls (10 young and 10 age-gender-matched old controls) and 20 patients with heart failure with preserved ejection fraction (HFpEF) were recruited. All had 4D flow CMR. Flow was quantified at the ascending and descending aorta levels. In addition, at the ascending aorta level, we quantified systolic flow displacement (FDs) and systolic flow reversal ratio (sFRR). The aortic conduit function was defined as the relative drop in systolic flow from the ascending to the descending aorta (∆Fs). Aortic reservoir function was defined as descending aortic diastolic stroke volume (DAo SVd). RESULTS: Both ∆Fs (R=0.51, p=0.001) and DAo SVd (R=-0.68, p=0.001) were significantly associated with ageing. Native T1 (R=0.51, p=0.001) and extracellular volume (R=0.51, p=0.001) showed maximum association with ∆Fs. ∆Fs significantly increased in HFpEF versus age-gender-matched controls (41±8% vs 52±12%, p=0.02). In multiple regression, only ∆Fs and DAo SVd were independent predictors of the estimated glomerular filtration rate (model R=0.77, p=0.0001). FDs was significantly associated with ∆Fs (R=0.4, p=0.01) and DAo SVd (R=-0.48, p=0.002), whereas sFRR was mainly associated with DAo SVd (R=-0.46, p=0.003). CONCLUSION: Both aortic conduit and reservoir function decline with age and this decline in aortic function is also independently associated with renal functional decline. Ascending aortic turbulent flow signatures are associated with loss of aortic conduit and reservoir functions. Finally, in HFpEF, aortic conduit and reservoir function demonstrate progressive decline. TRIALS REGISTRATION NUMBER: NCT05114785.
Asunto(s)
Relevancia Clínica , Insuficiencia Cardíaca , Volumen Sistólico , Función Ventricular Izquierda , Femenino , Humanos , Masculino , Aorta/diagnóstico por imagen , Aorta/fisiopatología , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/fisiopatología , Velocidad del Flujo Sanguíneo/fisiología , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/diagnóstico , Imagen por Resonancia Cinemagnética/métodos , Volumen Sistólico/fisiología , Función Ventricular Izquierda/fisiologíaRESUMEN
BACKGROUND: Variations in the aortomitral positional anatomy, including aortic root rotation appear to be related to variations in the location of the conduction system, including the bundle of His. However, little is known about their clinical significance. METHODS AND RESULTS: This study included 147 patients with normal ECGs who underwent mitral valve surgery. The aortomitral anatomy was classified using preoperative 3-dimensional transesophageal echocardiography, and postoperative conduction disorders, including atrioventricular block and bundle branch block, were analyzed. Variations classified as aortomitral appearance were designated as having a center appearance (85.7%, n=126/147) or lateral appearance (14.3%, n=21/147) on the basis of whether the aortic root was located at the center or was shifted to the left fibrous trigone side. Subsequently, those with a center appearance, aortic root rotation was classified as having a center rotation (83.3% [n=105/126]), in which the commissure of the left and noncoronary aortic leaflet was located at the center, lateral rotation (14.3% [n=18/126]), rotated to the left trigone side, or medial rotation (2.4% [n=3/126]), rotated to the right. The incidence of 3-month persistent new-onset conduction disorder was higher in the lateral appearance than the center appearance group (21.1% versus 5.0%; P=0.031) and higher in the lateral rotation than in the center or medial rotation groups (29.4% versus 1.0% versus 0.0%, respectively; P<0.001). CONCLUSIONS: Aortomitral variations can be classified using 3-dimensional transesophageal echocardiography. Lateral appearance and lateral rotation are risk factors for conduction disorders in mitral valve surgery.
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Bloqueo Atrioventricular , Ecocardiografía Tridimensional , Ecocardiografía Transesofágica , Válvula Mitral , Humanos , Masculino , Femenino , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Válvula Mitral/fisiopatología , Persona de Mediana Edad , Bloqueo Atrioventricular/etiología , Bloqueo Atrioventricular/fisiopatología , Bloqueo Atrioventricular/diagnóstico , Anciano , Estudios Retrospectivos , Electrocardiografía , Bloqueo de Rama/fisiopatología , Bloqueo de Rama/etiología , Factores de Riesgo , Aorta/diagnóstico por imagen , Aorta/cirugía , Aorta/fisiopatología , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Adulto , Resultado del Tratamiento , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico por imagenRESUMEN
Pulmonary hypertension is a group of diseases characterized by elevated pulmonary artery pressure and pulmonary vascular resistance with significant morbidity and mortality. The most prevalent type is pulmonary hypertension secondary to left heart disease (PH-LHD). The available experimental models of PH-LHD use partial pulmonary clamping by technically nontrivial open-chest surgery with lengthy recovery. We present a simple model in which the reduction of the cross-sectional area of the ascending aorta is achieved not by external clamping but by partial intravascular obstruction without opening the chest. In anesthetized rats, a blind polyethylene tubing was advanced from the right carotid artery to just above the aortic valve. The procedure is quick and easy to learn. Three weeks after the procedure, left heart pressure overload was confirmed by measuring left ventricular end-diastolic pressure by puncture (1.3 ± 0.2 vs. 0.4 ± 0.3 mmHg in controls, mean ± SD, P < 0.0001). The presence of pulmonary hypertension was documented by measuring pulmonary artery pressure by catheterization (22.3 ± 2.3 vs. 16.9 ± 2.7 mmHg, P = 0.0282) and by detecting right ventricular hypertrophy and increased muscularization of peripheral pulmonary vessels. Contributions of a precapillary vascular segment and vasoconstriction to the increased pulmonary vascular resistance were demonstrated, respectively, by arterial occlusion technique and by normalization of resistance by a vasodilator, sodium nitroprusside, in isolated lungs. These changes were comparable, but not additive, to those induced by an established pulmonary hypertension model, chronic hypoxic exposure. Intravascular partial aortic obstruction offers an easy model of pulmonary hypertension induced by left heart disease that has a vasoconstrictor and precapillary component.NEW & NOTEWORTHY We present a new, simple model of a clinically important type of pulmonary hypertension, that induced by left heart failure. Left ventricular pressure overload is induced in rats by inserting a blinded cannula into the ascending aorta via carotid artery access. This partial intravascular aortic obstruction, which does not require opening of the chest and prolonged recovery, causes pulmonary hypertension, which has a precapillary and vasoconstrictor as well as a vascular remodeling component.
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Aorta , Modelos Animales de Enfermedad , Hipertensión Pulmonar , Animales , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/etiología , Masculino , Ratas , Aorta/fisiopatología , Aorta/patología , Arteria Pulmonar/fisiopatología , Arteria Pulmonar/patología , Resistencia Vascular , Ratas Sprague-Dawley , Ratas Wistar , Hipertrofia Ventricular Derecha/fisiopatología , Hipertrofia Ventricular Derecha/etiologíaRESUMEN
The mechanisms underlying endothelial dysfunction in Type 1 and Type 2 diabetes (T1DM and T2DM) are unresolved. The red blood cells (RBCs) with increased arginase activity induce endothelial dysfunction in T2DM, but the implications of RBCs and the role of arginase inhibition in T1DM are unexplored. We aimed to investigate the differences in endothelial function in patients with T1DM and T2DM, with focus on RBCs and arginase. Thirteen patients with T1DM and twenty-six patients with T2DM, matched for HbA1c and sex were included. In vivo endothelium-dependent and -independent vasodilation (EDV and EIDV) were assessed by venous occlusion plethysmography before and after administration of an arginase inhibitor. RBCs were co-incubated with rat aortic segments for 18h followed by evaluation of endothelium-dependent (EDR) and -independent relaxation (EIDR) in isolated organ chambers. In vivo EDV, but not EIDV, was significantly impaired in patients with T2DM compared with patients with T1DM. Arginase inhibition resulted in improved EDV only in T2DM. RBCs from patients with T2DM induced impaired EDR but not EIDR in isolated aortic segments, whereas RBCs from patients with T1DM did not affect EDR nor EIDR. The present study demonstrates markedly impaired EDV in patients with T2DM in comparison with T1DM. In addition, it highlights the divergent roles of RBCs and arginase in mediating endothelial dysfunction in T1DM and T2DM. While endothelial dysfunction is mediated via RBCs and arginase in T2DM, these phenomena are not prominent in T1DM thereby indicating distinct differences in underlying mechanisms.
Asunto(s)
Arginasa , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Endotelio Vascular , Eritrocitos , Vasodilatación , Humanos , Arginasa/metabolismo , Arginasa/antagonistas & inhibidores , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/sangre , Masculino , Eritrocitos/enzimología , Eritrocitos/metabolismo , Femenino , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 1/sangre , Persona de Mediana Edad , Endotelio Vascular/fisiopatología , Animales , Adulto , Anciano , Aorta/fisiopatología , Inhibidores Enzimáticos/farmacologíaRESUMEN
Transcatheter aortic heart valve thrombosis (THVT) affects long-term valve durability, transvalvular pressure gradient and leaflet mobility. In this study, we conduct high-fidelity fluid-structure interaction simulations to perform Lagrangian particle tracing in a generic model with larger aortic diameters (THVT model) with and without neo-sinus which is compared to a model of unaffected TAVI patients (control model). Platelet activation indices are computed for each particle to assess the risk of thrombus formation induced by high shear stresses followed by flow stagnation. Particle tracing indicates that fewer particles contribute to sinus washout of the THVT model with and without neo-sinus compared to the control model (-34.9%/-34.1%). Stagnating particles in the native sinus of the THVT model show higher platelet activation indices than for the control model (+39.6% without neo-sinus, +45.3% with neo-sinus). Highest activation indices are present for particles stagnating in the neo-sinus of the larger aorta representing THVT patients (+80.2% compared to control). This fluid-structure interaction (FSI) study suggests that larger aortas lead to less efficient sinus washout in combination with higher risk of platelet activation among stagnating particles, especially within the neo-sinus. This could explain (a) a higher occurrence of thrombus formation in transcatheter valves compared to surgical valves without neo-sinus and (b) the neo-sinus as the prevalent region for thrombi in TAV. Pre-procedural identification of larger aortic roots could contribute to better risk assessment of patients and improved selection of a patient-specific anti-coagulation therapy.
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Válvula Aórtica , Modelos Cardiovasculares , Activación Plaquetaria , Trombosis , Humanos , Trombosis/fisiopatología , Trombosis/patología , Activación Plaquetaria/fisiología , Válvula Aórtica/patología , Válvula Aórtica/cirugía , Reemplazo de la Válvula Aórtica Transcatéter , Aorta/fisiopatologíaRESUMEN
In this work we present a novel methodology for the numerical simulation of patient-specific aortic dissections. Our proposal, which targets the seamless virtual prototyping of customized scenarios, combines an innovative two-step segmentation procedure with a CutFEM technique capable of dealing with thin-walled bodies such as the intimal flap. First, we generate the fluid mesh from the outer aortic wall disregarding the intimal flap, similarly to what would be done in a healthy aorta. Second, we create a surface mesh from the approximate midline of the intimal flap. This approach allows us to decouple the segmentation of the fluid volume from that of the intimal flap, thereby bypassing the need to create a volumetric mesh around a thin-walled body, an operation widely known to be complex and error-prone. Once the two meshes are obtained, the original configuration of the dissection into true and false lumen is recovered by embedding the surface mesh into the volumetric one and calculating a level set function that implicitly represents the intimal flap in terms of the volumetric mesh entities. We then leverage the capabilities of unfitted mesh methods, specifically relying on a CutFEM technique tailored for thin-walled bodies, to impose the wall boundary conditions over the embedded intimal flap. We tested the method by simulating the flow in four patient-specific aortic dissections, all involving intricate geometrical patterns. In all cases, the preprocess is greatly simplified with no impact on the computational times. Additionally, the obtained results are consistent with clinical evidence and previous research.
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Disección Aórtica , Simulación por Computador , Modelos Cardiovasculares , Humanos , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/fisiopatología , Aneurisma de la Aorta/diagnóstico por imagen , Aneurisma de la Aorta/fisiopatología , Aorta/fisiopatología , Aorta/diagnóstico por imagenRESUMEN
Hypertension, a disease with known sexual dimorphism, accelerates aging-associated arterial stiffening, partly because of the activation of matrix remodeling caused by increased biomechanical load. In this study, we tested the effect of biological sex and the role of the matrix remodeling enzyme lysyl oxidase-like 2 (LOXL2) in hypertension-induced arterial stiffening. Hypertension was induced by angiotensin II (ANG II) infusion via osmotic minipumps in 12- to 14-wk-old male and female mice. Blood pressure and pulse wave velocity (PWV) were measured noninvasively. Wire myography and uniaxial tensile testing were used to test aortic vasoreactivity and mechanical properties. Aortic wall composition was examined by histology and Western blotting. Uniaxial stretch of cultured cells was used to evaluate the effect of biomechanical strain. LOXL2's catalytic function was examined using knockout and inhibition. ANG II infusion-induced hypertension in both genotypes and sexes. Wild-type (WT) males exhibited arterial stiffening in vivo and ex vivo. Aortic remodeling with increased wall thickness, intralamellar distance, higher LOXL2, and collagen I and IV content was noted in WT males. Female mice did not exhibit increased PWV despite the onset of hypertension. LOXL2 depletion improved vascular reactivity and mechanics in hypertensive males. LOXL2 depletion improved aortic mechanics but worsened hypercontractility in females. Hypertensive cyclic strain contributed to LOXL2 upregulation in the cell-derived matrix in vascular smooth muscle cells (VSMCs) but not endothelial cells. LOXL2's catalytic function facilitated VSMC alignment in response to biomechanical strain. In conclusion, in males, arterial stiffening in hypertension is driven both by VSMC response and matrix remodeling. Females are protected from PWV elevation in hypertension. LOXL2 depletion is protective in males with improved mechanical and functional aortic properties. VSMCs are the primary source of LOXL2 in the aorta, and hypertension increases LOXL2 processing and shifts to collagen I accumulation. Overall, LOXL2 depletion offers protection in young hypertensive males and females.NEW & NOTEWORTHY We examined the effect of sex on the evolution of angiotensin II (ANG II)-induced hypertension and the role of lysyl oxidase-like 2 (LOXL2), an enzyme that catalyzes matrix cross linking. While ANG II led to hypertension and worsening vascular reactivity in both sexes, aortic remodeling and stiffening occurred only in males. LOXL2 depletion improved outcomes in males but not females. Thus males and females exhibit a distinct etiology of hypertension and LOXL2 is an effective target in males.
Asunto(s)
Aminoácido Oxidorreductasas , Angiotensina II , Hipertensión , Remodelación Vascular , Rigidez Vascular , Animales , Femenino , Masculino , Ratones , Aminoácido Oxidorreductasas/metabolismo , Aminoácido Oxidorreductasas/genética , Aorta/fisiopatología , Aorta/patología , Aorta/enzimología , Aorta/efectos de los fármacos , Aorta/metabolismo , Células Cultivadas , Modelos Animales de Enfermedad , Hipertensión/inducido químicamente , Hipertensión/fisiopatología , Hipertensión/enzimología , Hipertensión/metabolismo , Hipertensión/patología , Ratones Endogámicos C57BL , Ratones Noqueados , Músculo Liso Vascular/fisiopatología , Músculo Liso Vascular/enzimología , Músculo Liso Vascular/patología , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efectos de los fármacos , Miocitos del Músculo Liso/enzimología , Miocitos del Músculo Liso/patología , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , Factores SexualesRESUMEN
Type 2 diabetes (T2D) constitutes a major public health problem, and despite prevention efforts, this pandemic disease is one of the deadliest diseases in the world. In 2022, 6.7 million patients with T2D died prematurely from vascular complications. Indeed, diabetes increases the risk of myocardial infarction or stroke eightfold. The identification of the molecular factors involved in the occurrence of cardiovascular complications and their prevention are therefore major axes. Our hypothesis is that factors brought into play during physiological aging appear prematurely with diabetes progression. Our study focused on the aging of the extracellular matrix (ECM), a major element in the maintenance of vascular homeostasis. We characterized the morphological and functional aspects of aorta, with a focus on the collagen and elastic fibers of diabetic mice aged from 6 mo to nondiabetic mice aged 6 mo and 20 mo. The comparison with the two nondiabetic models (young and old) highlighted an exacerbated activity of proteases, which could explain a disturbance in the collagen accumulation and an excessive degradation of elastic fibers. Moreover, the generation of circulating elastin-derived peptides reflects premature aging of the ECM. These extracellular elements contribute to the appearance of vascular rigidity, often the origin of pathologies such as hypertension and atherosclerosis. In conclusion, we show that diabetic mice aged 6 mo present the same characteristics of ECM wear as those observed in mice aged 20 mo. This accelerated aortic wall remodeling could then explain the early onset of cardiovascular diseases and, therefore, the premature death of patients with T2D.NEW & NOTEWORTHY Aortic elastic fibers of young (6-mo old) individuals with diabetes degrade prematurely and exhibit an appearance like that found in aged (20-mo old) nondiabetic mice. Exacerbated elastolysis and elastin-derived peptide production are characteristic elements, contributing to early aortic wall rigidity and hypertension development. Therefore, limiting this early aging could be a judicious therapeutic approach to reduce cardiovascular complications and premature death in patients with diabetes.
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Aorta , Tejido Elástico , Matriz Extracelular , Síndrome Metabólico , Ratones Endogámicos C57BL , Rigidez Vascular , Animales , Tejido Elástico/metabolismo , Tejido Elástico/patología , Rigidez Vascular/fisiología , Ratones , Aorta/metabolismo , Aorta/patología , Aorta/fisiopatología , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Masculino , Síndrome Metabólico/metabolismo , Síndrome Metabólico/patología , Síndrome Metabólico/fisiopatología , Elastina/metabolismo , Colágeno/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/fisiopatología , Envejecimiento/patología , Envejecimiento/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Diabetes Mellitus Tipo 2/fisiopatología , Envejecimiento Prematuro/metabolismo , Envejecimiento Prematuro/patología , Envejecimiento Prematuro/fisiopatologíaRESUMEN
BACKGROUND: Aortic endothelial diastolic dysfunction is an early complication of diabetes and the abnormal differentiation of Th17 cells is involved in the development of diabetes. However, the exact role of exercise on regulating the Th17 cells differentiation and the underlying molecular mechanisms remain to be elucidated in diabetic mice. METHODS: db/db and db/m+ mice were randomly divided into exercise and sedentary groups. Mice in exercise group were exercised daily, 6 days/week, for 6 weeks and mice in sedentary groups were placed on a nonmoving treadmill for 6 weeks. Vascular endothelial function was measured via wire myograph and the frequencies of Th17 from peripheral blood in mice were assessed via flow cytometry. RESULTS: Our data showed that exercise improved insulin resistance and aortic endothelial diastolic function in db/db mice. In addition, the proportion of Th17 cells and IL-17A level in peripheral blood of db/db mice were significantly increased, and exercise could promote Th17 cell differentiation and reduce IL-17A level. More importantly, STAT3 or ROR-γt inhibitors could promote Th17 cell differentiation in db/db mice, while exercise significantly down-regulated p-STAT3/ROR-γt signaling in db/db mice, suggesting that exercise regulated Th17 differentiation through STAT3/ROR-γt signaling. CONCLUSIONS: This study demonstrated that exercise improved vascular endothelial function in diabetic mice via reducing Th17 cell differentiation through p-STAT3/ROR-γt pathway, suggesting exercise may be an important non-pharmacological intervention strategy for the treatment of diabetes-related vascular complications.
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Diferenciación Celular , Diabetes Mellitus Experimental , Interleucina-17 , Condicionamiento Físico Animal , Factor de Transcripción STAT3 , Células Th17 , Vasodilatación , Animales , Ratones , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Vasodilatación/fisiología , Factor de Transcripción STAT3/metabolismo , Diabetes Mellitus Experimental/fisiopatología , Diabetes Mellitus Experimental/terapia , Masculino , Interleucina-17/sangre , Interleucina-17/metabolismo , Endotelio Vascular/fisiopatología , Resistencia a la Insulina/fisiología , Transducción de Señal , Ratones Endogámicos C57BL , Aorta/fisiopatologíaAsunto(s)
Hemodinámica , Modelos Cardiovasculares , Humanos , Angiografía por Tomografía Computarizada , Simulación por Computador , Aorta/diagnóstico por imagen , Aorta/fisiopatología , Modelación Específica para el Paciente , Aortografía , Valor Predictivo de las Pruebas , Interpretación de Imagen Radiográfica Asistida por ComputadorRESUMEN
PURPOSE: Left atrium to aortic root ratio (LA/Ao) is an echocardiographic marker of hemodynamically significant patent ductus arteriosus (PDA). Since 2-dimensional measurement of the ratio is geometrically limited, left atrial volume (LAV) which has 3-dimensional characteristics was investigated. The aim of this study was to determine a correlation between LA/Ao ratio and LAV as well as holodiastolic flow reversal in preterm neonates with and without a PDA. METHODS: A retrospective evaluation of neonates with and without PDA was performed. Targeted neonatal echocardiography evaluation of LA/Ao and LAV was measured from parasternal long-axis view and the apical 4 and 2-chamber views, respectively. Univariate and linear regression analysis were performed. RESULTS: 200 patients were included of whom 158 (79.0%) had a PDA shunt. The median gestational age at the time of echo was 27.4 weeks (IQR: 25.7-29.4 weeks). The median LA/Ao ratio was 1.51 (IQR: 1.26-1.83) and median LAV indexed to weight was .91 mL/kg (IQR: .65-1.18 mL/kg). There was a significant correlation between LA/Ao and LAV indexed to weight in the PDA group (r2 = .080, p = .0003). LA/Ao ratio and LAV indexed to weight differed significantly between those with diastolic flow reversal versus no-flow reversal (LA/Ao, p = .003; LAV, p = .001). CONCLUSIONS: This study demonstrated a significant correlation between LA/Ao and LAV in preterm infants with PDA, with greater magnitude of discordance for LAV. The power of LAV versus LA/Ao in monitoring hemodynamically significant PDA requires prospective evaluation.
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Conducto Arterioso Permeable , Ecocardiografía , Atrios Cardíacos , Recien Nacido Prematuro , Humanos , Conducto Arterioso Permeable/fisiopatología , Conducto Arterioso Permeable/diagnóstico por imagen , Recién Nacido , Femenino , Masculino , Estudios Retrospectivos , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Ecocardiografía/métodos , Aorta/diagnóstico por imagen , Aorta/fisiopatologíaRESUMEN
BACKGROUND: Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia. METHODS: In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation. RESULTS: Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression. CONCLUSIONS: These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.
Asunto(s)
Modelos Animales de Enfermedad , Inflamasomas , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 9 de la Matriz , Ratones Endogámicos C57BL , Ratones Noqueados para ApoE , Proteína con Dominio Pirina 3 de la Familia NLR , Fenantrenos , Transducción de Señal , Quinasa Syk , Vasodilatación , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismo , Quinasa Syk/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Fenantrenos/farmacología , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Vasodilatación/efectos de los fármacos , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/fisiopatología , Vasodilatadores/farmacología , Fosforilación , Ratones , Aorta/efectos de los fármacos , Aorta/fisiopatología , Aorta/metabolismo , Aorta/enzimología , Apolipoproteínas ERESUMEN
OBJECTIVES: We aimed to cardiologically evaluate the consequences of glycosaminoglycan (GAG) accumulation in the large vessels of patients with mucopolysaccharidosis (MPS). METHODS: The left ventricular wall thickness, left ventricular mass (LVmass) were evaluated and aortic annulus diameter (AA), aortic sinus valsalva diameter (SV), sinotubular junction diameter (STJ), systolic aortic diameter (ADs), diastolic aortic diameter (ADd) body indices were obtained by dividing by the surface area. Aortic distensibility and stiffness index were obtained using aortic strain. Ejection fraction, mitral E and A velocities, mitral early diastolic tissue velocity (e'), E/A ratio, and E/e' ratio were evaluated. RESULTS: The LVED-i, LVmass-i, AA-i, SV-i, STJ-i, ADs-i, and ADd-i values were significantly higher in the MPS group. While the E and e' velocities and E/A ratio were significantly low in the MPS group, the A velocity and E/e' ratio were significantly high. While the stiffness index, SBP, and PP values were significantly higher in the MPS group, the aortic strain and distensibility were significantly lower. There was a correlation between the stiffness index and the aortic strain, distensibility, SBP, PP, and ventricular function. Cardiac function, aortic diameter, and aortic elasticity characteristics were similar between patients with MPS who received ERT and those who did not. CONCLUSIONS: In the MPS group, aortic elasticity properties were impaired, and aortic stiffness increased. ERT has positive effects on cardiac function, aortic diameter, and aortic stiffness in MPS patients. An increased LVmass-i and impaired ventricular geometric structure in patients with MPS may be associated with increased aortic stiffness.
Asunto(s)
Aorta , Elasticidad , Terapia de Reemplazo Enzimático , Mucopolisacaridosis , Rigidez Vascular , Humanos , Terapia de Reemplazo Enzimático/métodos , Masculino , Mucopolisacaridosis/tratamiento farmacológico , Mucopolisacaridosis/fisiopatología , Rigidez Vascular/efectos de los fármacos , Femenino , Niño , Adolescente , Elasticidad/efectos de los fármacos , Aorta/fisiopatología , Aorta/efectos de los fármacos , Aorta/diagnóstico por imagen , Adulto Joven , Adulto , Pronóstico , Preescolar , Estudios de Seguimiento , Ecocardiografía , Estudios de Casos y ControlesRESUMEN
The maximum blood flow velocity through the aortic valve (AVmax) using Doppler transthoracic echocardiography (TTE) is important in assessing the severity of aortic stenosis (AS). The right parasternal (RP) approach has been reported to be more useful than the apical approach, but the anatomical rationale has not been studied. We aimed to clarify the influence of the angle formed by the ascending aorta and left ventricle on Doppler analysis by TTE (Sep-Ao angle) and three-dimensional multidetector computed tomography (3D-MDCT) in patients with AS. A total of 151 patients evaluated using the RP approach and 3D-MDCT were included in this study. The Sep-Ao angle determined using TTE was compared with that determined using 3D-MDCT analysis. In MDCT analysis, the left ventricular (LV) axis was measured in two ways and the calcification score was calculated simultaneously. The Sep-Ao angle on TTE was consistent with that measured using 3D-MDCT. In patients with an acute Sep-Ao angle, the Doppler angle in the apical approach was larger, potentially underestimating AVmax. Multivariate analysis revealed that an acute Sep-Ao angle, large Doppler angle in the apical approach, smaller Doppler angle in the RP approach, and low aortic valve calcification were independently associated with a higher AVmax in the RP approach than in the apical approach. The Sep-Ao angle measured using TTE reflected the 3D anatomical angle. In addition to measurements using the RP approach, technical adjustments to minimize the Doppler angle to avoid bulky calcification should always be noted for accurate assessment.