ABSTRACT
Pituitary hormone deficiency, hypopituitarism, is a dysfunction resulting from numerous etiologies, which can be complete or partial, and is therefore heterogeneous. This heterogeneity makes it difficult to interpret the results of scientific studies with these patients.Adequate treatment of etiologies and up-to-date hormone replacement have improved morbidity and mortality rates in patients with hypopituitarism. As GH replacement is not performed in a reasonable proportion of patients, especially in some countries, it is essential to understand the known consequences of GH replacement in each subgroup of patients with this heterogeneous dysfunction.In this review on hypopituitarism, we will address some particularities regarding insulin resistance, which is no longer common in these patients with hormone replacement therapy based on current guidelines, metabolic syndrome and its relationship with changes in BMI and body composition, and to vascular complications that need to be prevented taking into account the individual characteristics of each case to reduce mortality rates in these patients.
Subject(s)
Hypopituitarism , Insulin Resistance , Metabolic Syndrome , Humans , Hypopituitarism/etiology , Hypopituitarism/metabolism , Insulin Resistance/physiology , Metabolic Syndrome/metabolism , Metabolic Syndrome/complications , Hormone Replacement Therapy , Vascular Diseases/etiology , Vascular Diseases/metabolism , Human Growth Hormone/deficiency , Human Growth Hormone/metabolismABSTRACT
Introducción: La isquemia anal aguda con gangrena es una entidad infrecuente, con escasa literatura publicada al respecto, cuyas cifras de mortalidad descritas se sitúan en un 20 por ciento - 40 por ciento de los casos. Debe considerarse en ancianos con enfermedad aterosclerótica que presenten síntomas gastrointestinales inferiores y shock hipotensivo. Puede ser causada por oclusión vascular aguda, enfermedad vascular grave o un estado de bajo flujo, aunque en algunos casos se presenta sin enfermedad vascular preexistente. Objetivo: Presentar la literatura existente acerca del manejo diagnóstico y terapéutico de la isquemia de canal anal en base a un caso clínico diagnosticado y tratado de urgencia en el hospital "Marina Baixa". Caso clínico: Se presenta un caso de isquemia espontánea de canal anal en paciente de 76 años de edad con morbilidad cardiovascular asociada. Debuta como cuadro séptico sin evidencia de causa desencadenante. Conclusiones: Las pruebas endoscópicas y radiológicas deben realizarse con urgencia y la valoración quirúrgica está siempre justificada en estos pacientes debido a la alta tasa de mortalidad descrita en el manejo conservador del cuadro. En casos graves, la reanimación preoperatoria y cirugía urgente para resecar el segmento gangrenoso es necesaria. Sin embargo, el tratamiento de la proctitis isquémica aguda es controvertido y depende, en parte, del estado basal del paciente y los hallazgos clínicos, siendo importante examinar otras posibles etiologías de proctitis isquémica y así determinar qué pacientes necesitan intervención quirúrgica temprana en comparación con una actitud más conservadora(AU)
Introduction: Acute ischemic gangrene of the anus is an infrequent entity, with little published literature, whose reported mortality figures are 20-40 percent of cases. It should be considered in elderlies with atherosclerotic disease who present lower gastrointestinal symptoms and hypotensive shock. It can be caused by acute vascular occlusion, severe vascular disease, or a low-flow state, although in some cases it presents without pre-existing vascular disease. Objective: To present the existing literature on diagnostic and therapeutic management of ischemia of the anal canal upon the base of a clinical case diagnosed and treated as an urgency at Marina Baixa hospital. Clinical case: The case is presented of a 76-year-old patient with spontaneous ischemia of the anal canal and associated cardiovascular morbidity. It debuts as a septic condition without evidence of a triggering cause. Conclusions: Endoscopic and radiological tests should be performed urgently. Surgical assessment is always justified in these patients, due to the high mortality rate described in the conservative management of the condition. In severe cases, preoperative resuscitation and urgent surgery to resect the gangrenous segment is necessary. However, managment of acute ischemic proctitis is controversial and depends, in part, on the patient's baseline status and clinical findings, while it is important to examine other possible etiologies of ischemic proctitis and thus determine which patients need early surgical intervention compared to a more conservative attitude(AU)
Subject(s)
Humans , Female , Aged , Anal Canal/injuries , Surgical Procedures, Operative/methods , Vascular Diseases/etiology , Ischemia/diagnostic imaging , Review Literature as Topic , Conservative Treatment/methodsABSTRACT
Endothelial dysfunction (ED) is a key factor for the development of cardiovascular diseases. Due to its chronic, life-threatening nature, ED only can be studied experimentally in animal models. Therefore, this work was aimed to characterize a murine model of ED induced by a daily intraperitoneal administration of angiotensin II (AGII) for 10 weeks. Oxidative stress, inflammation, vascular remodeling, hypertension, and damage to various target organs were evaluated in treated animals. The results indicated that a chronic intraperitoneal administration of AGII increases the production of systemic soluble VCAM, ROS and ICAM-1 expression, and the production of TNFα, IL1ß, IL17A, IL4, TGFß, and IL10 in the kidney, as well as blood pressure levels; it also promotes vascular remodeling and induces non-alcoholic fatty liver disease, glomerulosclerosis, and proliferative retinopathy. Therefore, the model herein proposed can be a representative model for ED; additionally, it is easy to implement, safe, rapid, and inexpensive.
Subject(s)
Angiotensin II/administration & dosage , Disease Models, Animal , Endothelium, Vascular/metabolism , Vascular Diseases/metabolism , Angiotensin II/toxicity , Animals , Endothelium, Vascular/drug effects , Endothelium, Vascular/pathology , Infusions, Parenteral , Intercellular Adhesion Molecule-1/metabolism , Interleukins/metabolism , Kidney/metabolism , Kidney/pathology , Liver/metabolism , Liver/pathology , Male , Mice , Mice, Inbred C57BL , Oxidative Stress , Transforming Growth Factor beta/metabolism , Tumor Necrosis Factor-alpha/metabolism , Vascular Cell Adhesion Molecule-1/metabolism , Vascular Diseases/etiology , Vascular Diseases/pathology , Vascular RemodelingSubject(s)
COVID-19/complications , Sickle Cell Trait/complications , Vascular Diseases/diagnosis , COVID-19/virology , Fatal Outcome , Humans , Male , Middle Aged , RNA, Viral/genetics , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Vascular Diseases/etiology , Vascular Diseases/therapyABSTRACT
Spontaneous coronary artery dissection is an uncommon cause of acute coronary syndrome that predominantly affects women without cardiovascular risk factors. In transplant patients, spontaneous coronary artery dissection is an extremely rare condition, having been described in only three patients, in whom vascular damage secondary to the use of anticalcineurinics is postulated as a probable mechanism. We report a spontaneous coronary dissection in a female who received a heart transplant at 34 years of age. The diagnosis was made in a follow-up coronary angiography three years after transplantation, supplemented with optical coherence tomography. A percutaneous coronary revascularization of the involved artery was performed, with good immediate results and at one year of follow-up.
Subject(s)
Coronary Vessel Anomalies , Heart Transplantation , Vascular Diseases , Coronary Angiography , Coronary Vessel Anomalies/diagnostic imaging , Dissection , Female , Heart Transplantation/adverse effects , Humans , Vascular Diseases/diagnostic imaging , Vascular Diseases/etiologyABSTRACT
Smooth muscle cell (SMC) contractility is essential to vessel tone maintenance and blood pressure regulation. In response to vasoconstrictors, calcium-dependent mechanisms promote the activation of the regulatory myosin light chain, leading to increased cytoskeleton tension that favors cell shortening. In contrast, SMC maintain an intrinsic level of a contractile force independent of vasoconstrictor stimulation and sustained SMC contraction beyond the timescale of calcium-dependent mechanisms suggesting the involvement of additional players in the contractile response. Focal adhesions (FAs) are conceivable candidates that may influence SMC contraction. They are required for actin-based traction employed by cells to sense and respond to environmental cues in a process termed mechanotransduction. Depletion of FA proteins impairs SMC contractility, producing arteries that are prone to dissection because of a lack of mechanical stability. Here, we discuss the role of calcium-independent FA signaling mechanisms in SMC contractility. We speculate that FA signaling contributes to the genesis of a variety of SMC phenotypes and discuss the potential implications for mechanical homeostasis in normal and diseased states.
Subject(s)
Focal Adhesions/metabolism , Mechanotransduction, Cellular , Muscle, Smooth, Vascular/physiology , Myocytes, Smooth Muscle/physiology , Animals , Humans , Vascular Diseases/etiology , Vascular Diseases/metabolismABSTRACT
Spontaneous coronary artery dissection is an uncommon cause of acute coronary syndrome that predominantly affects women without cardiovascular risk factors. In transplant patients, spontaneous coronary artery dissection is an extremely rare condition, having been described in only three patients, in whom vascular damage secondary to the use of anticalcineurinics is postulated as a probable mechanism. We report a spontaneous coronary dissection in a female who received a heart transplant at 34 years of age. The diagnosis was made in a follow-up coronary angiography three years after transplantation, supplemented with optical coherence tomography. A percutaneous coronary revascularization of the involved artery was performed, with good immediate results and at one year of follow-up.
Subject(s)
Humans , Female , Vascular Diseases/etiology , Vascular Diseases/diagnostic imaging , Heart Transplantation/adverse effects , Coronary Vessel Anomalies/diagnostic imaging , Coronary Angiography , DissectionABSTRACT
Resumen A 29 year old female with a past medical history of systemic lupus erythematosus, diagnosed 15 years earlier, presents with lupus nephritis, currently on peritoneal dialysis. She had myopericarditis in 2012 and is currently on immunosuppressants. The patient began with exertional dyspnea and angina 2 weeks before admission. An echocardiogram was performed, reporting severe mitral and tricuspid insufficiency. Afterwards, the patient presented with resting angina associated with an adrenergic and vagal response. Initially, rheumatology ruled out autoimmune activity caused by lupus. We performed a coronary angiogram based on clinical presentation, EKG changes and biomarkers, finding a trivascular coronary artery disease classified as a Markis I coronary artery ectasia and a coronary dissection of the ramus intermedius and the circumflex, posterior to the first obtuse marginal artery. Cardiothoracic surgery considered intervention with a coronary bridge posterior to the dissection of the intermedius ramus artery, marginal obtuse and posterolateral artery, as well as a mitral valve replacement and a tricuspid valve repair. Coronary dissection is more common in women (70%), clinical presentation varies from unstable angina to sudden death. In lupus nephritis, it is an uncommon form of extra renal vasculitis. Treatment depends on the number of arteries affected, as well as the haemodynamic state of the patient. It is imperative to individualize treatment options.
Abstract Se presenta el caso de una paciente de 29 años con antecedente de lupus eritematoso sistémico diagnosticado 15 años antes, que desarrolló nefropatía lúpica actualmente en diálisis peritoneal, cuadro de miopericarditis en 2012 y bajo tratamiento inmunosupresor. Inició con deterioro de su clase funcional por disnea y angina 2 semanas previas al ingreso. Se le realizó ecocardiograma, el cual reportó insuficiencias mitral y tricuspídea graves. Posteriormente presentó angina en reposo asociada a descarga adrenérgica y vagal. A su ingreso se descarta actividad lúpica por reumatología. Por presentación clínica, cambios en electrocardiograma y biomarcadores, se realizó cateterismo cardiaco, que reportó enfermedad coronaria trivascular con ectasia coronaria Markis I y disección coronaria de ramo intermedio y circunfleja posterior a la primera marginal obtusa. Se consideró por el servicio de cirugía cardiotorácica realizar intervención con puente coronario posterior a disección del ramo intermedio, marginal obtusa y posterolateral, así como cambio valvular mitral y plastia tricuspídea. La disección coronaria espontánea es más frecuente en las mujeres (70%); puede presentarse como angina inestable y hasta como muerte súbita. La asociación con lupus eritematoso sistémico es poco frecuente, con una incidencia del 0.42%. En la nefropatía lúpica es una manifestación poco frecuente de vasculitis extrarrenal. El tratamiento de elección depende del número de vasos afectados y del estado hemodinámico, por lo que es necesario individualizarlo para cada paciente.
Subject(s)
Humans , Female , Adult , Vascular Diseases/congenital , Coronary Vessel Anomalies/etiology , Lupus Erythematosus, Systemic/complications , Vascular Diseases/etiologyABSTRACT
Se presenta el caso de una paciente de 29 años con antecedente de lupus eritematoso sistémico diagnosticado 15 años antes, que desarrolló nefropatía lúpica actualmente en diálisis peritoneal, cuadro de miopericarditis en 2012 y bajo tratamiento inmunosupresor. Inició con deterioro de su clase funcional por disnea y angina 2 semanas previas al ingreso. Se le realizó ecocardiograma, el cual reportó insuficiencias mitral y tricuspídea graves. Posteriormente presentó angina en reposo asociada a descarga adrenérgica y vagal. A su ingreso se descarta actividad lúpica por reumatología. Por presentación clínica, cambios en electrocardiograma y biomarcadores, se realizó cateterismo cardiaco, que reportó enfermedad coronaria trivascular con ectasia coronaria Markis I y disección coronaria de ramo intermedio y circunfleja posterior a la primera marginal obtusa. Se consideró por el servicio de cirugía cardiotorácica realizar intervención con puente coronario posterior a disección del ramo intermedio, marginal obtusa y posterolateral, así como cambio valvular mitral y plastia tricuspídea. La disección coronaria espontánea es más frecuente en las mujeres (70%); puede presentarse como angina inestable y hasta como muerte súbita. La asociación con lupus eritematoso sistémico es poco frecuente, con una incidencia del 0.42%. En la nefropatía lúpica es una manifestación poco frecuente de vasculitis extrarrenal. El tratamiento de elección depende del número de vasos afectados y del estado hemodinámico, por lo que es necesario individualizarlo para cada paciente.
Subject(s)
Coronary Vessel Anomalies/etiology , Lupus Erythematosus, Systemic/complications , Vascular Diseases/congenital , Adult , Female , Humans , Vascular Diseases/etiologyABSTRACT
OBJECTIVES: Vascular and biliary complications associated with liver transplants involve high morbidity and mortality as well as cost overrun for health systems. Efforts to prioritize their prevention require not only clinical information but also information on costs that reflect the economic burden on health systems. The objective of this study was to describe cost overrun incurred from early vascular and biliary complications after liver transplant. METHODS: This cases series included liver transplant patients treated at the San Vicente Foundation University Hospital, Rionegro, Antioquia, from January 1, 2013, to December 31, 2018. All liver transplant patients treated during the above period were included; the absence of clinical records on the variables of interest was considered the exclusion criterion. A probabilistic analysis of patient cost was performed. Monte Carlo simulations as well as a 1-way sensitivity analysis per transplant cost component were performed. RESULTS: Records from 154 patients were assessed. The average patient age was 56.9 (SD 10.9) years; 42.9% of patients were women. Of all, 36.4% patients were classified as Child C, and the average Model for End-Stage Liver Disease score was 19.6. The average cost for patients without complications was $27 834.82, whereas that for patients with early vascular complications was $36 747.83 and for those with early biliary complications was $38 523.74. CONCLUSION: Early vascular and biliary complications after liver transplant increase healthcare costs, with the increase being significant in patients with biliary complications.
Subject(s)
Biliary Tract Diseases/etiology , Health Care Costs/standards , Liver Transplantation/adverse effects , Vascular Diseases/etiology , Aged , Biliary Tract Diseases/economics , Biliary Tract Diseases/epidemiology , Colombia/epidemiology , Female , Health Care Costs/statistics & numerical data , Hospitals/statistics & numerical data , Humans , Liver/physiopathology , Liver Transplantation/economics , Liver Transplantation/methods , Male , Middle Aged , Retrospective Studies , Vascular Diseases/economics , Vascular Diseases/epidemiologyABSTRACT
PURPOSE: To report the device performance and safety for the Surfacer Inside-Out access catheter system in patients with thoracic central venous obstruction (TCVO) requiring central venous access (CVA). MATERIALS AND METHODS: Five sites prospectively enrolled 30 patients requiring a tunneled dialysis catheter between February 2017 and September 2018 in the SAVE (Surfacer System to Facilitate Access in Venous Obstructions) registry. Patient demographics, medical history, and type of TCVO were documented at enrollment. Device performance and adverse events were collected during the procedure and upon hospital discharge. Twenty-nine of the 30 patients enrolled required CVA for hemodialysis. Retrospective classification of TCVOs according to SIR reporting standards showed 9 patients (30%) had Type 4 obstructions, 8 (26.7%) had Type 3, 5 (16.7%) had Type 2, and 8 (26.7%) had Type 1 obstruction. RESULTS: Central venous catheters (CVCs) were successfully placed in 29 of 30 patients (96.7%). The procedure was discontinued in 1 patient due to vascular anatomical tortuosity. All 29 patients with successful CVC placement achieved adequate catheter patency and tip positioning. There were no device-related adverse events, catheter malposition, or intra- or postprocedural complications. Mean time from device insertion to removal for the 29 patients who successfully completed the procedure was 24 ± 14.9 (range, 6-70) minutes. Mean fluoroscopy time was 6.8 ± 4.5 (range, 2.2-25.5) minutes. CONCLUSIONS: The Surfacer Inside-Out procedure provided an alternative option to restore right-sided CVA in patients with TCVO.
Subject(s)
Brachiocephalic Veins , Catheterization, Central Venous/instrumentation , Catheters, Indwelling , Central Venous Catheters , Jugular Veins , Renal Dialysis , Subclavian Vein , Vascular Diseases , Vena Cava, Superior , Adult , Aged , Aged, 80 and over , Brachiocephalic Veins/diagnostic imaging , Catheterization, Central Venous/adverse effects , Constriction, Pathologic , Equipment Design , Europe , Female , Humans , Jugular Veins/diagnostic imaging , Male , Middle Aged , Prospective Studies , Registries , South America , Subclavian Vein/diagnostic imaging , Vascular Diseases/diagnostic imaging , Vascular Diseases/etiology , Vena Cava, Superior/diagnostic imagingABSTRACT
BACKGROUND: Modern imaging plays a central role in the care of obese patients, and there is an integral focus on its use and accessibility in individuals who have alterations of various in various organs. The objective in this study was to perform an echographic analysis of musculoskeletal system disorders, endothelial dysfunction and the left ventricle (LV) in obese rats. METHODS: Sprague Dawley rats (250 ± 5 g) were obtained and divided into two groups: the control (C) group was fed with a standard diet, and the obese (Ob) group was fed hyper caloric diet with a high fructose-fat content for 4 months. Body weight, cholesterol, triglycerides, glucose, inflammatory cytokines and adhesion molecules (ICAM-1, VCAM-1) were measured. Additionally, two-dimensional echocardiography, abdominal ultrasound and musculoskeletal system studies were performed in the lower extremities. RESULTS: The body weight in the Ob group was increased compared to that in the control group, (p < 0.001); in addition, increased glucose, cholesterol and triglyceride concentrations (p < 0.05) as well as increased levels of the adhesion molecules ICAM-1 and, VCAM-1 (p < 0.01) were found in the Ob group vs the C group. On ultrasound, 75% of the Ob group presented fatty liver and distal joint abnormalities. CONCLUSION: Obese rats exhibit endothelial dysfunction and musculoskeletal changes, also, fatty liver and articular cysts in the posterior region of the distal lower- extremity joints.
Subject(s)
Endothelium, Vascular/diagnostic imaging , Heart/diagnostic imaging , Liver/diagnostic imaging , Musculoskeletal System/diagnostic imaging , Obesity/diagnosis , Anatomy, Cross-Sectional , Animals , Endothelium, Vascular/pathology , Endothelium, Vascular/physiopathology , Heart/physiopathology , Intercellular Adhesion Molecule-1/metabolism , Liver/physiopathology , Male , Musculoskeletal Diseases/diagnosis , Musculoskeletal Diseases/etiology , Musculoskeletal Diseases/pathology , Musculoskeletal Diseases/physiopathology , Musculoskeletal System/pathology , Musculoskeletal System/physiopathology , Myocardium/pathology , Obesity/complications , Obesity/physiopathology , Rats , Rats, Sprague-Dawley , Ultrasonography , Vascular Diseases/diagnosis , Vascular Diseases/etiology , Vascular Diseases/pathology , Vascular Diseases/physiopathology , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/pathology , Ventricular Dysfunction, Left/physiopathologyABSTRACT
El virus provoca una reacción vascular inflamatoria en el endotelio arterial de varios órganos, entre ellos el pulmón (afectando el intercambio de gases en la membrana alveolo-capilar), de ahí la insuficiencia respiratoria, pero también afecta a otros órganos. Cuando una persona adquiere el nuevo coronavirus, este entra a los pulmones e infecta directamente a los alvéolos, que absorben el aire que respiramos. En casos graves, esos sacos de aire se llenan de líquido, restándole espacio para el oxígeno. Esto es lo que se conoce como neumonía por covid-19. Los alvéolos se infectan y activan el sistema inmunitario, lo que puede conducir a una tormenta de citoquinas. El SARS-Cov-2 también causa coágulos de sangre, lo que ha provocado que personas de entre 30 y 40 años mueran por accidentes cerebrovasculares. La enfermedad inflama los vasos sanguíneos y eventualmente puede dañar las arterias coronarias que llevan sangre al corazón. Entonces, cabe preguntarse: ¿no será que, además de afectar la membrana alvéolo-capilar en el pulmón, e interferir en el intercambio de oxígeno, afecta el endotelio arterial y provoca una microangiopatía diseminada con coagulopatía? Ojalá se encuentre pronto la respuesta. Miles de los mejores científicos del mundo están trabajando para intentar comprender el nuevo coronavirus; han descifrado su código genético y producido decenas de artículos que proponen posibles tratamientos y vacunas. Recomiendo un interesante artículo publicado por los Dres. Alfonso Papa y Giustino Varrassi, que creo que coincide con mi opinión sobre la afectación vascular en el SARS-Cov-2 (covid-19),1 disponible en: https://www.researchgate.net/publication/341553008. (AU)
The virus causes an inflammatory vascular reaction in the arterial endothelium of various organs, including the lung (affecting gas exchange in the alveolar-capillary membrane), hence the respiratory failure, but it also affects other organs. When a person acquires the new coronavirus, it enters to the lungs and directly infects the alveoli, which absorb the air we breathe. In severe cases, these air sacs fill with fluid, taking up space for oxygen. It is known as covid-19 pneumonia. The alveoli become infected and activate the immune system and can lead to a cytokine storm. SARS-Cov-2 also causes blood clots, which has caused people in their 30s to 40s to die from strokes. The disease inflames the blood vessels and can eventually damage the coronary arteries that carry blood to the heart. So, it is worth asking: Is it not that, in addition to affecting the alveolar-capillary membrane in the lung, and interfering with oxygen exchange, it affects the arterial endothelium and causes disseminated micro-angiopathy with coagulopathy? Hopefully the answers will be found soon. Thousands of the world's best scientists are working to try to understand the new coronavirus. They cracked their genetic code and have produced dozens of articles suggesting possible treatments and vaccines. I add an interesting article published by Drs. Alfonso Papa and Giustino Varrassi. I think it matches my opinion about vascular involvement in SARS-Cov-2 (covid-19),1 available at: https://www.researchgate.net/publication/341553008. (AU)
Subject(s)
Humans , SARS-CoV-2/pathogenicity , COVID-19/complications , COVID-19/physiopathology , Respiratory Insufficiency/etiology , Vascular Diseases/etiology , Blood Coagulation Disorders/etiologyABSTRACT
Pregnancy-associated spontaneous coronary artery dissection (PASCAD) accounts for less than 5% of spontaneous coronary artery dissection cases and is comparatively more fulminant or clinically aggressive. Several factors associated with PASCAD include black ethnicity, multiparity, hypertension, advanced maternal age, and age at first childbirth. This atypical case highlights a preeclamptic patient presenting with an ST-segment elevation myocardial infarction in which multivessel dissection of both the left anterior descending and right coronary arteries were deemed co-culprit lesions for the index event.
Subject(s)
Coronary Vessel Anomalies/etiology , Pre-Eclampsia/diagnosis , Vascular Diseases/congenital , Adult , Cineangiography , Coronary Vessel Anomalies/diagnosis , Coronary Vessel Anomalies/diagnostic imaging , Electrocardiography , Female , Humans , Male , Pre-Eclampsia/pathology , Pregnancy , ST Elevation Myocardial Infarction/complications , ST Elevation Myocardial Infarction/diagnosis , Vascular Diseases/diagnosis , Vascular Diseases/diagnostic imaging , Vascular Diseases/etiologyABSTRACT
OBJECTIVE: Hyperhomocysteinemia (HHcy) is a potent risk factor for diabetic cardiovascular diseases. We have previously reported that hyperhomocysteinemia potentiates type 1 diabetes mellitus-induced inflammatory monocyte differentiation, vascular dysfunction, and atherosclerosis. However, the effects of hyperhomocysteinemia on vascular inflammation in type 2 diabetes mellitus (T2DM) and the underlying mechanism are unknown. Approach and Results: Here, we demonstrate that hyperhomocysteinemia was induced by a high methionine diet in control mice (homocysteine 129 µmol/L), which was further worsened in T2DM db/db mice (homocysteine 180 µmol/L) with aggravated insulin intolerance. Hyperhomocysteinemia potentiated T2DM-induced mononuclear cell, monocyte, inflammatory monocyte (CD11b+Ly6C+), and M1 macrophage differentiation in periphery and aorta, which were rescued by folic acid-based homocysteine-lowering therapy. Moreover, hyperhomocysteinemia exacerbated T2DM-impaired endothelial-dependent aortic relaxation to acetylcholine. Finally, transfusion of bone marrow cells depleted for Ly6C by Ly6c shRNA transduction improved insulin intolerance and endothelial-dependent aortic relaxation in hyperhomocysteinemia+T2DM mice. CONCLUSIONS: Hyperhomocysteinemia potentiated systemic and vessel wall inflammation and vascular dysfunction partially via inflammatory monocyte subset induction in T2DM. Inflammatory monocyte may be a novel therapeutic target for insulin resistance, inflammation, and cardiovascular complications in hyperhomocysteinemia+T2DM.
Subject(s)
Antigens, Ly/genetics , Atherosclerosis/complications , Diabetes Mellitus, Type 2/genetics , Hyperhomocysteinemia/complications , Monocytes/metabolism , Vascular Diseases/etiology , Animals , Cell Differentiation/genetics , Disease Models, Animal , Endothelium, Vascular/metabolism , Female , Hyperhomocysteinemia/genetics , Insulin/therapeutic use , Insulin Resistance , Macrophages/metabolism , Mice , Random Allocation , Risk Factors , Sensitivity and Specificity , Vascular Diseases/physiopathologyABSTRACT
OBJECTIVE: Evaluate the performance of the Vascular Complications Risk Score in two public referral centers for interventional cardiology. METHOD: Subsample analysis of the Vascular Complications Risk Score, which was developed and validated in the catheterization laboratories of three cardiology referral centers (two public, one private) with a cutoff of <3 for no risk of developing vascular complications and ≥3 for risk. In this new analysis, we excluded data from the private facility, and only included participants from the original (validation) cohort of the two public hospitals. RESULTS: Among the 629 patients studied, 11.8% had vascular complications; of these, 1.8% were major and 10% minor. Among the patients with a score <3, 310 (94.5%) presented no vascular complications; of those with a score ≥3, 50 (17%) developed complications. Of those who developed vascular complications, 18 scored <3; two of these had major complications. CONCLUSION: This subanalysis confirms the ability of the Vascular Complications Risk core to predict low risk of vascular complications in patients with a score < 3.