Pubfacts - Scientific Publication Data
  • Categories
  • |
  • Journals
  • |
  • Authors
  • Login
  • Categories
  • Journals

Search Our Scientific Publications & Authors

Publications
  • Publications
  • Authors
find publications by category +
Translate page:

Oxidized phospholipid modification of lipoprotein(a): Epidemiology, biochemistry and pathophysiology.

Authors:
Marlys L Koschinsky Michael B Boffa

Atherosclerosis 2022 05;349:92-100

Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada, N6A 5B7; Department of Biochemistry, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, N6A 5B7, Canada.

Oxidized phospholipids (OxPL) are key mediators of the pro-atherosclerotic effects of oxidized lipoproteins. They are particularly important for the pathogenicity of lipoprotein(a) (Lp(a)), which is the preferred lipoprotein carrier of phosphocholine-containing OxPL in plasma. Indeed, elevated levels of OxPL-apoB, a parameter that almost entirely reflects the OxPL on Lp(a), are a potent risk factor for atherothrombotic diseases as well as calcific aortic valve stenosis. A substantial fraction of the OxPL on Lp(a) are covalently bound to the KIV domain of apo(a), and the strong lysine binding site (LBS) in this kringle is required for OxPL addition. Using apo(a) species lacking OxPL modification - by mutating the LBS - has allowed direct assessment of the role of apo(a) OxPL in Lp(a)-mediated pathogenesis. The OxPL on apo(a) account for numerous harmful effects of Lp(a) on monocytes, macrophages, endothelial cells, smooth muscle cells, and valve interstitial cells documented both in vitro and in vivo. In addition, the mechanisms underlying these effects have begun to be unraveled by identifying the cellular receptors that respond to OxPL, the intracellular signaling pathways turned on by OxPL, and the changes in gene and protein expression evoked by OxPL. The emerging picture is that the OxPL on Lp(a) are central to its pathobiology. The OxPL modification may explain why Lp(a) is such a potent risk factor for cardiovascular disease despite being present at concentrations an order of magnitude lower than LDL, and they account for the ability of elevated Lp(a) to cause both atherothrombotic disease and calcific aortic valve stenosis.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2022.04.001DOI Listing
May 2022

Publication Analysis

Top Keywords

oxpl
13
oxpl lpa
12
calcific aortic
8
lpa potent
8
aortic valve
8
valve stenosis
8
risk factor
8
oxpl modification
8
potent risk
8
lpa
7
endothelial cells
4
macrophages endothelial
4
cells smooth
4
oxpl apoa
4
monocytes macrophages
4
smooth muscle
4
muscle cells
4
lpa monocytes
4
effects lpa
4
harmful effects
4

Keyword Occurance

Similar Publications

Oxidized phospholipid modification of lipoprotein(a): Epidemiology, biochemistry and pathophysiology.

Authors:
Marlys L Koschinsky Michael B Boffa

Atherosclerosis 2022 05;349:92-100

Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada, N6A 5B7; Department of Biochemistry, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, N6A 5B7, Canada.

Oxidized phospholipids (OxPL) are key mediators of the pro-atherosclerotic effects of oxidized lipoproteins. They are particularly important for the pathogenicity of lipoprotein(a) (Lp(a)), which is the preferred lipoprotein carrier of phosphocholine-containing OxPL in plasma. Indeed, elevated levels of OxPL-apoB, a parameter that almost entirely reflects the OxPL on Lp(a), are a potent risk factor for atherothrombotic diseases as well as calcific aortic valve stenosis. Read More

View Article and Full-Text PDF
May 2022
Similar Publications

Deletion of the scavenger receptor Scarb1 in osteoblast progenitors does not affect bone mass.

Authors:
Michela Palmieri Teenamol E Joseph Charles A O'Brien Horacio Gomez-Acevedo Stavros C Manolagas Elena Ambrogini

PLoS One 2022 29;17(3):e0265893. Epub 2022 Mar 29.

Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases and Center for Musculoskeletal Disease Research, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR, United States of America.

The scavenger receptor class B member 1 (SR-B1 or Scarb1) is a cell surface receptor for high density lipoproteins. It also binds oxidized low density lipoproteins and phosphocholine-containing oxidized phospholipids (PC-OxPL), which adversely affect bone homeostasis. Overexpression of a single chain form of the antigen-binding domain of E06 IgM-a natural antibody that recognizes PC-OxPL-increases trabecular and cortical bone mass in female and male mice by stimulating bone formation. Read More

View Article and Full-Text PDF
April 2022
Similar Publications

Association of Lipoproteins with Neutrophil Extracellular Traps in Patients with Abdominal Aortic Aneurysm.

Authors:
Annika Brandau Nahla Ibrahim Johannes Klopf Hubert Hayden Maria Ozsvar-Kozma Taras Afonyushkin Sonja Bleichert Lukas Fuchs Viktoria Watzinger Verena Nairz Emely Manville Veronika Kessler Herbert Stangl Wolf Eilenberg Christoph Neumayer Christine Brostjan

Biomedicines 2022 Jan 20;10(2). Epub 2022 Jan 20.

Division of Vascular Surgery, Department of General Surgery, Medical University of Vienna, Vienna General Hospital, 1090 Vienna, Austria.

Neutrophil extracellular traps (NETs) are DNA-protein structures released by neutrophils in response to various stimuli, including oxidized, low-density lipoprotein (oxLDL). Accumulating evidence suggests a role for NETs in the pathogenesis of abdominal aortic aneurysm (AAA). In this study, we investigated the potential association of lipoprotein particles and NETs in AAA in comparison to non-AAA control groups. Read More

View Article and Full-Text PDF
January 2022
Similar Publications

Lipoprotein(a), a Lethal Player in Calcific Aortic Valve Disease.

Authors:
Jiahui Hu Hao Lei Leiling Liu Danyan Xu

Front Cell Dev Biol 2022 27;10:812368. Epub 2022 Jan 27.

Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.

Calcified aortic valve disease (CAVD) is the most common valvular cardiovascular disease with increasing incidence and mortality. The primary treatment for CAVD is surgical or transcatheter aortic valve replacement and there remains a lack of effective drug treatment. Recently, lipoprotein (a) (Lp(a)) has been considered to play a crucial role in CAVD pathophysiology. Read More

View Article and Full-Text PDF
January 2022
Similar Publications

Oxidized Phospholipids Promote NETosis and Arterial Thrombosis in LNK(SH2B3) Deficiency.

Authors:
Huijuan Dou Andriana Kotini Wenli Liu Trevor Fidler Kaori Endo-Umeda Xiaoli Sun Malgorzata Olszewska Tong Xiao Sandra Abramowicz Mustafa Yalcinkaya Brian Hardaway Sotirios Tsimikas Xuchu Que Alexander Bick Conor Emdin Pradeep Natarajan Eirini P Papapetrou Joseph L Witztum Nan Wang Alan R Tall

Circulation 2021 12 30;144(24):1940-1954. Epub 2021 Nov 30.

Molecular Medicine, Columbia University Medical Center, New York (H.D., W.L., T.F., K.E.-U., T.X., S.A., M.Y., B.H., N.W., A.R.T.).

Background: LNK/SH2B3 inhibits Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling by hematopoietic cytokine receptors. Genome-wide association studies have shown association of a common single nucleotide polymorphism in (R262W, T allele) with neutrophilia, thrombocytosis, and coronary artery disease. We have shown that ) reduces LNK function and that LNK-deficient mice display prominent platelet-neutrophil aggregates, accelerated atherosclerosis, and thrombosis. Read More

View Article and Full-Text PDF
December 2021
Similar Publications
}
© 2022 PubFacts.
  • About PubFacts
  • Privacy Policy
  • Sitemap