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Cited by 101Atherosclerosis and Cardiovascular DiseasesLipoproteins and Cardiovascular HealthCholesterol and Lipid Metabolism

Effects of PCSK9 Targeting: Alleviating Oxidation, Inflammation, and Atherosclerosis

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Punch, Emily, Klein, Justus, Diaba‐Nuhoho, Patrick, Morawietz, Henning, Garelnabi, Mahdi·2022·Journal of the American Heart Association
DOI 10.1161/jaha.121.023328PMC PMC9238481
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Abstract

Characterized as a chronic inflammatory disease of the large arteries, atherosclerosis is the primary cause of cardiovascular disease, the leading contributor of morbidity and mortality worldwide. Elevated plasma cholesterol levels and chronic inflammation within the arterial plaque are major mediators of plaque initiation, progression, and instability. In 2003, the protein PCSK9 (proprotein convertase subtilisin/kexin 9) was discovered to play a critical role in cholesterol regulation, thus becoming a key player in the mechanisms behind atherosclerotic plaque development. Emerging evidence suggests that PCSK9 could potentially have effects on atherosclerosis that are independent of cholesterol levels. The objective of this review was to discuss the role on PCSK9 in oxidation, inflammation, and atherosclerosis. This function activates proinflammatory cytokine production and affects oxidative modifications within atherosclerotic lesions, revealing its more significant role in atherosclerosis. Although a variety of evidence demonstrates that PCSK9 plays a role in atherosclerotic inflammation, the direct mechanism of involvement is still unknown, driving a gap in knowledge to such a predominant player in cardiovascular disease. Investigation of proteins structurally related to PCSK9 may interestingly be the link in unveiling the mechanistic role of this protein’s involvement in oxidation and inflammation. Importantly, the unique structure of PCSK9 bears structural homology to a one‐of‐a‐kind domain found in the metabolic protein resistin, which is responsible for many of the same inflammatory outcomes as PCSK9. Closing this gap in knowledge of PCSK9`s role in atherosclerotic oxidation and inflammation will provide fundamental information for understanding, preventing, and treating cardiovascular disease.

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Cited by

Sorted by citations

Authors
Punch, E., Klein, J., Diaba‐Nuhoho, P., Morawietz, H., & Garelnabi, M.
Affiliations
  • University of Massachusetts Lowell (US)
  • University Hospital Carl Gustav Carus (DE)
Corresponding author
  • Morawietz, Henning
  • Garelnabi, Mahdi
ORCID
Venue
Journal of the American Heart Association
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2022-02
Volume
11
Issue
3
Pages
e023328-e023328
ISSN
2047-9980 (ISSN-L)
DOI
10.1161/jaha.121.023328
PMC
PMC9238481
OpenAlex
W4206622478
Cited by
101
References
10
Citations by year
2026: 23 · 2025: 20 · 2024: 31 · 2023: 21 · 2022: 6
FWCI
2.05
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Journal of the American Heart Association (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Qucosa (Saxon State and University Library Dresden) (publishedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Deutsche Forschungsgemeinschaft
  • Else Kröner-Fresenius-Stiftung
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords
PCSK9, atherosclerosis, oxidative modification, inflammation, inflammatory cytokines, cholesterol regulation, cardiovascular disease, resistin, PCSK9 inhibitors, atherosclerotic plaque
MeSH terms
Proprotein Convertase 9, Cardiovascular Diseases, Humans, Inflammation, Atherosclerosis, Plaque, Atherosclerotic

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