Mecanismos de envejecimiento vascular: ¿Qué podemos aprender del síndrome de progeria de Hutchinson-Gilford? / Mechanisms of vascular aging: What can we learn from Hutchinson-Gilford progeria syndrome?

El envejecimiento es el principal factor de riesgo de enfermedad cardiovascular (ECV) y su prevalencia está aumentando progresivamente debido en gran parte al incremento de la esperanza de vida a nivel mundial. En este contexto, es fundamental establecer cuáles son los mecanismos por los que el envejecimiento promueve el desarrollo de ECV, con el objetivo de reducir su incidencia. La aterosclerosis y la insuficiencia cardiaca contribuyen de manera significativa a la morbimortalidad por ECV asociada a la edad. El síndrome de progeria de Hutchinson-Gilford (HGPS) se caracteriza por un envejecimiento prematuro que cursa también con ECV acelerada. Se trata de un trastorno genético raro causado por la expresión de progerina, una forma mutada de la prelamina A. La progerina induce aterosclerosis masiva y alteraciones electrofisiológicas en el corazón, promueve el envejecimiento y finalmente la muerte prematura a una edad media de 14,6 años, principalmente por infarto de miocardio o ictus cerebral. En esta revisión se discuten las principales alteraciones estructurales y funcionales que afectan al sistema vascular durante el envejecimiento fisiológico y prematuro, así como los mecanismos que subyacen a la aterosclerosis y al envejecimiento exagerados inducidos por la prelamina A y la progerina. Dado que ambas proteínas se expresan en individuos sin HGPS y muchas de las características del envejecimiento normal se presentan en la progeria, la investigación en el ámbito del HGPS podría contribuir a la identificación de nuevos mecanismos implicados en el envejecimiento cardiovascular fisiológico

Aging is the main risk factor for cardiovascular disease (CVD). The increased prevalence of CVD is partly due to the global increase in life expectancy. In this context, it is essential to identify the mechanisms by which aging induces CVD, with the ultimate aim of reducing its incidence. Both atherosclerosis and heart failure significantly contribute to age-associated CVD morbidity and mortality. Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by the synthesis of progerin, which is noted for accelerated aging and CVD. This mutant form of prelamin A induces generalised atherosclerosis, vascular calcification, and cardiac electrophysiological abnormalities, leading to premature aging and death, mainly due to myocardial infarction and stroke. This review discusses the main vascular structural and functional abnormalities during physiological and premature aging, as well as the mechanisms involved in the exacerbated CVD and accelerated aging induced by the accumulation of progerin and prelamin A. Both proteins are expressed in non-HGPS individuals, and physiological aging shares many features of progeria. Research into HGPS could therefore shed light on novel mechanisms involved in the physiological aging of the cardiovascular system

Nuclear protein extraction from frozen porcine myocardium

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Protocols for the extraction of nuclear proteins have been developed for cultured cells and fresh tissue, but sometimes only frozen tissue is available. We have optimized the homogenization procedure and subsequent fractionation protocol for the preparation of nuclear protein extracts from frozen porcine left ventricular (LV) tissue. This method gave a highly reproducible protein yield (6.5 ± 0.7% of total protein; mean±SE, n = 9) and a 6-fold enrichment of the nuclear marker protein B23. The nuclear protein extracts were essentially devoid of cytosolic, myofilament, and histone proteins. Compared to nuclear extracts from fresh LV tissue, some loss of nuclear proteins to the cytosolic fraction was observed. Using this method, we studied the distribution of tyrosine-phosphorylated signal transducer and activator of transcription 3 (PY-STAT3) in LV tissue of animals treated with the â-agonist dobutamine. Upon treatment, PY-STAT3 increased 30.2 ± 8.5-fold in total homogenates, but only 6.9 ± 2.1-fold (n = 4, P = 0.03) in nuclear protein extracts. Of all PY-STAT3 formed, only a minor fraction appeared in the nuclear fraction. This simple and reproducible protocol yielded nuclear protein extracts that were highly enriched in nuclear proteins with almost complete removal of cytosolic and myofilament proteins. This nuclear protein extraction protocol is therefore well-suited for nuclear proteome analysis of frozen heart tissue collected in biobanks (AU)

Marcadores tumorales urinarios para el cáncer vesical / Urinary tumor markers for bladder cancer

En los últimos años se han aprobado las pruebas de marcadores tumorales no invasivos para el diagnóstico del carcinoma vesical ImmunoCyt/uCyt+, BTA TRAK, BTA STAT, NMP22, NMP22 BladderChek y UroVysion, sin embargo, ninguno de estos nuevos marcadores ha demostrado una sensibilidad y especificidad de manera simultánea lo suficientemente elevadas que permita sustituir la cistoscopia. Globalmente han demostrado mayor sensibilidad que la citología de orina, con una sensibilidad y especificidad medias del 64,80% y del 71-95% respectivamente, y valores predictivos positivo y negativo medios del 49-84% y del 79-95%. Las pruebas BTA TRAK, BTA stat, NMP22 y NMP22 BladderChek están limitadas por el elevado número de falsos positivos en casos de litiasis, infección urinaria o hematuria y debido a su baja especificidad, no se recomienda el uso de BTA TRAK, BTA stat, NMP22 Y NMP22 BladderChek sin descartar primero la presencia de una enfermedad genitouriana benigna o maligna aparte del cáncer de vejiga. Solamente UroViysion alcanza un 80% de sensibilidad y un 94% de especificidad (AU)

Over the last years, the non-invasive diagnostic tests, ImmunoCyt /uCyt+, BTA TRAK, BTA stat, NMP22, NMP22 BladderChek and UroVysion, for the diagnosis of bladder carcinomas have been approved. Nonetheless, these new markers have failed to achieve high enough sensitivity and specificity to replace cystoscopy. Globally they have shown higher sensitivity than urine cytology with a median sensitivity and specificity of 64-80% and 71-95% respectively, and median positive and negative predictive values of 49-84% and 79to 95%. The BTA TRAK, BTA stat, NMP22 and NMP22 BladderChek test have the limitation of a high false positive rate in the context of litbiasis, urinary infection or haematuria and do to its low specificity, the use of BTA TRAK, BTA stat, NMP22 and NMP22 BladderChek without first ruling out the presence of a benign or malignant genitourinary disease beside bladder cancer is not recommended. Only the UroVysion test reaches 80% sensitibity and 94% specificity (AU)