Resumen
El reciente descubrimiento de un receptor de (pro-)renina, al que se unen pro-renina y renina, ha renovado el interés por la pro-renina. Esta es el precursor de la renina sintetizada en el aparato yuxtaglomerular y se produce también extrarrenalmente. En situaciones clínicas como la diabetes, hay valores elevados de prorenina en plasma que se asocian a daño microvascular. Tras unirse al receptor, la pro-renina experimenta una activación no proteolítica que consiste en la separación del prosegmento, lo que le confiere capacidad catalítica para generar angiotensina I a partir del angiotensinógeno. Por otra parte, la unión de (pro-)renina al receptor induce la activación de cinasas que intervienen en la diferenciación celular (neuronal) y en la formación de citocinas fibrogénicas y otros mediadores de lesión tisular. Además de ejercer efectos relacionados con el sistema renina-angiotensina-aldosterona (SRAA), el receptor (pro-)renina se une a la ATPasa vacuolada, implicada en la acidificación intracelular y en otras importantes funciones para la viabilidad celular. El uso de un péptido similar a una parte del prosegmento de la pro-renina que impide la unión de pro-renina al receptor ha dado resultados discrepantes en modelos experimentales. En algunos casos, ha sido eficaz para prevenir o atenuar la nefropatía diabética y la fibrosis cardiaca y en otros no. Los inhibidores directos de la renina (IDR) tienen capacidad de unirse a la (pro-)renina ligada al receptor e impedir su acción catalítica. La mayoría de los estudios no evidencian la capacidad de los IDR para suprimir los efectos no catalíticos (no dependientes de la angiotensina II) del complejo (pro-)renina-receptor. Todavía hay muchos interrogantes sobre el papel de la pro-renina en la generación tisular e intracelular de la angiotensina II, los efectos intracelulares inducidos por la unión pro-renina-receptor y sobre la relevancia de la función del receptor (pro-)renina no relacionado con el SRA. Asimismo, surgen muchas cuestiones sobre posibles agentes que bloqueen el receptor (pro-)renina y sobre el efecto de los IDR en las consecuencias celulares, dependientes e independientes de la angiotensina II, de la interacción (pro-)renina-receptor.
Palabras clave
Pro-renina
Receptor (pro-)renina
Inhibidores directos de la renina
Aliskiren
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