Abstrakt

Konwertazy probiałkowe (PCs, proprotein convertases) to rodzina 9 proteaz serynowych (PC1/3, PC2, furyna, PC4, PC5/6, PACE4, PC7, SKI-1), której przedstawicielem jest również konwertaza probiałkowa typu 9 o aktywności subtylizyny/keksyny (PCSK9). Poszczególni członkowie tej rodziny, są głównym elementem w potranslacyjnej obróbce białek prekursorowych, prowadzącej do powstania biologicznie czynnych cząsteczek, takich jak hormony, enzymy, czynniki transkrypcyjne oraz czynniki wzrostu. W związku ze zdolnością aktywacji dużej liczby substratów, PCs odgrywają znaczącą rolę w przebiegu procesów fizjologicznych, takich jak embriogeneza, aktywność ośrodkowego układu nerwowego, metabolizm lipidów, a także w stanach patofizjologicznych m.in. infekcjach wirusowych i bakteryjnych, osteoporozie, hiperglikemii, chorobach sercowo-naczyniowych, neurodegeneracyjnych oraz nowotworowych. Zahamowanie funkcji konwertazy proproteiny typu 9 o aktywności subtylizyny/ keksyny (PCSK9, proprotein convertase subtilisin/kexin 9) przez przeciwciała, takie jak alirokumab czy ewolokumab zmniejsza tempo degradacji receptora LDL (lipoproteina o małej gęstości). Wiąże się to z redukcją stężenia cholesterolu LDL w osoczu, którego normalizacja jest jednym z głównych celów służących ograniczeniu ryzyka sercowo-naczyniowego. Inhibitory PCSK9 (alirokumab, ewolokumab, bococizumab) zostały stworzone m.in. z myślą o pacjentach, u których mimo stosowania optymalnych dawek dostępnych leków hipolipemizujących (statyn, ezetymibu) nie udało się uzyskać pożądanych wartości stężeń cholesterolu LDL we krwi. Wydaje się, że ze względu na dużą skuteczność, przyszłe zastosowanie inhibitorów PCSK9 (PCSK9i) w codziennej praktyce klinicznej będzie bardziej powszechne. Uwzględniając działania plejotropowe substancji dotychczas stosowanych w hiperlipidemii, takich jak statyny, omówiono piśmiennictwo pod kątem innych, poza hipolipemizującymi, możliwych skutków działania inhibitorów PCSK9 oraz oceniono ich potencjalne zalety lub wady.

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