Table 1.
A list of researches of effects of PCSK9 on sepsis.
| Participants/model of study | Study type | Main results | Reference |
|---|---|---|---|
| Patients with sepsis | A single-centre observational cohort study | Plasma PCSK9 levels are greatly increased in sepsis. During sepsis, PCSK9 levels are highly correlated with the development of subsequent multiple organ failure. |
Boyd et al. [20] |
| Male Pcsk9 knockout (Pcsk9−/−) mice Patients with septic shock (VASST derivation cohort/SPH validation cohort) Healthy, nonobese subjects GENE population |
An experimental study Muticentre observational cohort studies |
Reduced PCSK9 function is associated with increased pathogen lipid clearance via the LDL-R, a decreased inflammatory response, and improved septic shock outcome. | Walley et al. [21] |
| Patients with sepsis or sepsis shock | A retrospective observational study | Patients with multiple PCSK9 LOF alleles had lower risk of 1-year death or infection-related readmission compared with WT/single LOF groups. | Genga et al. [22] |
| Wild-type, PCSK9 knockout (KO), and PCSK9 transgenic mice | An experimental study | PCSK9 deficiency confers protection against systemic bacterial dissemination, organ pathology, and tissue inflammation, particularly in the lungs and liver, while PCSK9 overexpression exacerbates multiorgan pathology as well as the hypercoagulable and proinflammatory states in early sepsis. | Dwivedi et al. [25] |
| Patients with Gram-positive septic shock | A multicentre observational cohort study | Patients with PCSK9 LOF allele had significantly higher 28-day survival than those with no LOF alleles. | Leung et al. [26] |
| Patients hospitalized with infection | A retrospective cohort study | PCSK9 genetic variants were not significantly associated with risk of sepsis or the outcomes (cardiovascular failure and in-hospital death) of sepsis. | Feng et al. [27] |
| Patients with bacterial infections admitted to intensive care units | A cross-sectional study | There was no significant association between PCSK9 levels and either the severity of disease (APACHE II, SOFA, and GCS) indices or resistance to antibiotics. | Jamialahmadi et al. [28] |
| Female C57BL/6 mice | An experimental study | Inflammation state (LPS, zymosan, turpentine, etc.) stimulates PCSK9 expression | Feingold et al. [43] |
| C57Bl/6J wild-type and Ldlr-/- mice Pcsk9+/+ and Pcsk9-/- mice |
An experimental study | PCSK9 inhibition provides no protection from LPS-induced mortality in mice. | Berger et al. [29] |
| Patients with septic shock | A subanalysis of the Albumin Italian Outcome Sepsis (ALBIOS) study | Patients with septic shock presenting with lower plasma PCSK9 levels experienced higher mortality rate. | Vecchié et al. [23] |
The table summarized the experimental and clinical evidence on the role of PCSK9 and sepsis. PCSK9: proprotein convertase subtilisin/kexin type 9; LDL-R: low-density lipoprotein cholesterol receptors; KO: knockout; WT: wild type; LOF: loss of function; LPS: lipopolysaccharide.