Cited by 101Atherosclerosis and Cardiovascular DiseasesCholesterol and Lipid MetabolismLipoproteins and Cardiovascular Health

Acidification of the intimal fluid: the perfect storm for atherogenesis

Open access
Öörni, Katariina, Rajamäki, Kristiina, Nguyen, Su Duy, Lähdesmäki, Katariina, Plihtari, Riia, Lee-Rueckert, Miriam, Kovanen, Petri T.·2015·Journal of Lipid Research

Abstract

Atherosclerotic lesions are often hypoxic and exhibit elevated lactate concentrations and local acidification of the extracellular fluids. The acidification may be a consequence of the abundant accumulation of lipid-scavenging macrophages in the lesions. Activated macrophages have a very high energy demand and they preferentially use glycolysis for ATP synthesis even under normoxic conditions, resulting in enhanced local generation and secretion of lactate and protons. In this review, we summarize our current understanding of the effects of acidic extracellular pH on three key players in atherogenesis: macrophages, apoB-containing lipoproteins, and HDL particles. Acidic extracellular pH enhances receptor-mediated phagocytosis and antigen presentation by macrophages and, importantly, triggers the secretion of proinflammatory cytokines from macrophages through activation of the inflammasome pathway. Acidity enhances the proteolytic, lipolytic, and oxidative modifications of LDL and other apoB-containing lipoproteins, and strongly increases their affinity for proteoglycans, and may thus have major effects on their retention and the ensuing cellular responses in the arterial intima. Finally, the decrease in the expression of ABCA1 at acidic pH may compromise cholesterol clearance from atherosclerotic lesions. Taken together, acidic extracellular pH amplifies the proatherogenic and proinflammatory processes involved in atherogenesis.

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Registry

Crossref · 10.1194/jlr.r050252

Cites

162 of 162 references verified0 citation errors · 0 not checkable

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  • Continual hydrolysis and re-esterification of droplet cholesterol is a futile cycle that wastes ATP and contributes to premature death of foam cells in poorly oxygenated atherosclerotic regions.

    “the continual hydrolysis and re-esterification of droplet cholesterol constitutes a futile cycle that wastes ATP and thereby contributes to the premature death of the foam cells in poorly oxygenated regions of atherosclerotic lesions24,25.”

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Authors
Öörni, K., Rajamäki, K., Nguyen, S. D., Lähdesmäki, K., Plihtari, R., Lee-Rueckert, M., & Kovanen, P. T.
Affiliations
Wihuri Research Institute (FI)
Corresponding author
Öörni, Katariina
Venue
Journal of Lipid Research
Publisher
Elsevier BV
Published
2015-02
Volume
56
Issue
2
Pages
203-214
ISSN
0022-2275 (ISSN-L)
OpenAlex
W2131894828
Cited by
101
References
163
Citations by year
2026: 8 · 2025: 16 · 2024: 11 · 2023: 4 · 2022: 14 · 2021: 12 · 2020: 10 · 2019: 7 · 2018: 7 · 2017: 6 · 2016: 6
FWCI
0.39
Type
journal article
Language
en
Open access
Locations
  • Journal of Lipid Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Suomen Kulttuurirahasto
  • Sydäntutkimussäätiö
  • Wihuri Research Institute
  • Jenny ja Antti Wihurin Rahasto
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
extracellular pH, atherogenesis, macrophages, lactate, glycolysis, inflammasome, inflammatory cytokines, apoB-containing lipoproteins, LDL modification, HDL cholesterol, ABCA1, cholesterol efflux, proteoglycans, phagocytosis, antigen presentation
MeSH terms
Animals, Apolipoproteins, Humans, Lipoproteins, Phospholipases, Proteoglycans, Tunica Intima, Atherosclerosis

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