The Role of PCSK9 in Infectious Diseases

Laura       Magnasco; Chiara       Sepulcri; Roberta    Maria    Antonello; Stefano       Di Bella; Laura       Labate; Roberto       Luzzati; Daniele    Roberto    Giacobbe; Matteo       Bassetti
doi:10.2174/0929867328666210714160343
Abstract

Background: In recent years, many aspects of the physiological role of PCSK9 have been elucidated, in particular regarding its role in lipid metabolism, cardiovascular risk but also its role in innate immunity. Increasing evidence is available on the involvement of PCSK9 in the pathogenesis of viral infections, mainly HCV, as well as in the regulation of host response to bacterial infections, mainly sepsis and septic shock. Moreover, the action of PCSK9 has been investigated as a crucial step in the pathogenesis of malaria infection and disease severity.
Objective: Aim of this paper is to review available published literature on the role of PCSK9 in a wide array of infectious diseases.
Conclusion: Besides the ongoing investigation on PCSK9 inhibition among HIV-infected patients for the treatment of HIV- and ART-related hyperlipidemia, preclinical studies indicate how PCSK9 is involved in reducing the replication of HCV. Moreover, a protective role of PCSK9 inhibition has also been proposed against dengue and SARS-CoV-2 viral infections. Interestingly, high plasmatic PCSK9 levels have been described in patients with sepsis. Finally, a loss of function in the PCSK9-encoding gene has been reported to possibly reduce mortality in malaria infection.
Keywords: HCV, HIV, sepsis, protozoal infection, viral infection, bacterial infection, immunity.
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DOI https://dx.doi.org/10.2174/0929867328666210714160343	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

The Role of PCSK9 in Infectious Diseases

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