Plasminogen missense variants and their involvement in cardiovascular and inflammatory disease.

Autor:	Brito-Robinson T; Department of Chemistry and Biochemistry and the W.M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN, United States., Ayinuola YA; Department of Chemistry and Biochemistry and the W.M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN, United States., Ploplis VA; Department of Chemistry and Biochemistry and the W.M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN, United States., Castellino FJ; Department of Chemistry and Biochemistry and the W.M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2024 Jun 25; Vol. 11, pp. 1406953. Date of Electronic Publication: 2024 Jun 25 (Print Publication: 2024).
DOI:	10.3389/fcvm.2024.1406953
Abstrakt:	Human plasminogen (PLG), the zymogen of the fibrinolytic protease, plasmin, is a polymorphic protein with two widely distributed codominant alleles, PLG/Asp 453 and PLG/Asn 453 . About 15 other missense or non-synonymous single nucleotide polymorphisms (nsSNPs) of PLG show major, yet different, relative abundances in world populations. Although the existence of these relatively abundant allelic variants is generally acknowledged, they are often overlooked or assumed to be non-pathogenic. In fact, at least half of those major variants are classified as having conflicting pathogenicity, and it is unclear if they contribute to different molecular phenotypes. From those, PLG/K 19 E and PLG/A 601 T are examples of two relatively abundant PLG variants that have been associated with PLG deficiencies (PD), but their pathogenic mechanisms are unclear. On the other hand, approximately 50 rare and ultra-rare PLG missense variants have been reported to cause PD as homozygous or compound heterozygous variants, often leading to a debilitating disease known as ligneous conjunctivitis. The true abundance of PD-associated nsSNPs is unknown since they can remain undetected in heterozygous carriers. However, PD variants may also contribute to other diseases. Recently, the ultra-rare autosomal dominant PLG/K 311 E has been found to be causative of hereditary angioedema (HAE) with normal C1 inhibitor. Two other rare pathogenic PLG missense variants, PLG/R 153 G and PLG/V 709 E, appear to affect platelet function and lead to HAE, respectively. Herein, PLG missense variants that are abundant and/or clinically relevant due to association with disease are examined along with their world distribution. Proposed molecular mechanisms are discussed when known or can be reasonably assumed. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (© 2024 Brito-Robinson, Ayinuola, Ploplis and Castellino.)
Databáze:	MEDLINE
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