RESUMEN
An association between high serum calcium/phosphate and cardiovascular events or death is well-established. However, a mechanistic explanation of this correlation is lacking. Here, we examined the role of calciprotein particles (CPPs), nanoscale bodies forming in the human blood upon its supersaturation with calcium and phosphate, in cardiovascular disease. The serum of patients with coronary artery disease or cerebrovascular disease displayed an increased propensity to form CPPs in combination with elevated ionised calcium as well as reduced albumin levels, altogether indicative of reduced Ca2+-binding capacity. Intravenous administration of CPPs to normolipidemic and normotensive Wistar rats provoked intimal hyperplasia and adventitial/perivascular inflammation in both balloon-injured and intact aortas in the absence of other cardiovascular risk factors. Upon the addition to primary human arterial endothelial cells, CPPs induced lysosome-dependent cell death, promoted the release of pro-inflammatory cytokines, stimulated leukocyte adhesion, and triggered endothelial-to-mesenchymal transition. We concluded that CPPs, which are formed in the blood as a result of altered mineral homeostasis, cause endothelial dysfunction and vascular inflammation, thereby contributing to the development of cardiovascular disease.
Asunto(s)
Angina de Pecho/fisiopatología , Isquemia Encefálica/fisiopatología , Cloruro de Calcio/sangre , Enfermedad de la Arteria Coronaria/fisiopatología , Células Endoteliales/patología , Infarto del Miocardio/fisiopatología , Fosfatos/sangre , Angina de Pecho/sangre , Angina de Pecho/genética , Animales , Aorta/metabolismo , Aorta/patología , Isquemia Encefálica/sangre , Isquemia Encefálica/genética , Cloruro de Calcio/química , Estudios de Casos y Controles , Muerte Celular , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/genética , Células Endoteliales/metabolismo , Transición Epitelial-Mesenquimal , Floculación , Regulación de la Expresión Génica , Humanos , Inflamación , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Leucocitos/metabolismo , Leucocitos/patología , Lisosomas/metabolismo , Lisosomas/patología , Masculino , Infarto del Miocardio/sangre , Infarto del Miocardio/genética , Fosfatos/química , Cultivo Primario de Células , Ratas , Ratas Wistar , Factores de Transcripción de la Familia Snail/genética , Factores de Transcripción de la Familia Snail/metabolismo , Túnica Íntima/metabolismo , Túnica Íntima/patología , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: The aim of this study was to assess significance of serum neutrophil gelatinase-associated lipocalin (sNGAL) and cystatin C (sCC) in prediction of adverse cardiovascular outcome after ST-segment elevation myocardial infarction (STEMI). METHODS: We recruited 357 consecutive patients who were admitted to the hospital within 24 h after onset of STEMI. On the 1st and 12th-14th day after hospital admission, we measured levels of sNGAL and sCC. We also determined presence of renal dysfunction (RD), defined as glomerular filtration rate < 60 mL/min/1.73 m2. After 3 years of follow-up, we performed a logistic regression and assessed the value of RD, sNGAL, and sCC in prediction of combined endpoint, defined as cardiovascular death or any cardiovascular complication. RESULTS: RD, sCC level ≥ 1.9 mg/L, and sNGAL level ≥ 1.25 ng/mL on the 12th-14th day of hospitalization were associated with a 1.6-fold, 1.9-fold, and 2.9-fold higher risk of adverse cardiovascular outcome, respectively. Area under the ROC curve was the highest for the model based on sNGAL level compared to the models based on sCC level or RD presence. CONCLUSIONS: Measurement of sNGAL level in patients with STEMI on the 12th-14th day after hospital admission may improve prediction of adverse cardiovascular outcome.
Asunto(s)
Cistatina C/sangre , Tasa de Filtración Glomerular/fisiología , Lipocalina 2/sangre , Insuficiencia Renal/etiología , Infarto del Miocardio con Elevación del ST/sangre , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Insuficiencia Renal/diagnóstico , Insuficiencia Renal/epidemiología , Infarto del Miocardio con Elevación del ST/complicaciones , Infarto del Miocardio con Elevación del ST/mortalidad , Siberia/epidemiología , Tasa de Supervivencia/tendencias , Factores de TiempoRESUMEN
BACKGROUND: The aim of this study was to evaluate the plasma levels of bone turnover markers (BTMs) in male patients with stable angina depending on the bone mineral density (BMD), coronary atherosclerosis (CA) and coronary artery calcification (CAC). METHODS: We recruited 112 males with verified stable angina. All the patients underwent coronary angiography, multislice spiral computed tomography, and dual-energy X-ray absorptiometry. Plasma levels of BTMs were measured by enzyme-linked immunosorbent assay. RESULTS: Osteopoenia and osteoporosis were reported in 90 (80.4%) and 34 (30.4%) patients, respectively. Multivessel coronary artery disease, severe CA and CAC, decreased cathepsin K plasma level, and increased osteocalcin plasma level were significantly more prevalent in patients with osteopoenia/osteoporosis compared to the subjects with normal BMD. Patients with severe CA and CAC had significantly reduced cathepsin K plasma levels. CONCLUSIONS: We revealed a significant association of osteopoenia/osteoporosis with severe CA and CAC in males with stable angina. Cathepsin K and osteocalcin plasma levels may be suggested as the significant markers of osteopoenia/osteoporosis. In addition, cathepsin K plasma level can be also a valuable marker of severe CA and CAC.