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

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Acidification of the intimal fluid: the perfect storm for atherogenesis

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

DOI 10.1194/jlr.r050252PMC PMC4306676

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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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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
ORCID: Öörni, Katariina
Rajamäki, Kristiina
Kovanen, Petri T.
Venue: Journal of Lipid Research
Publisher: Elsevier BV
Published: 2015-02
Volume: 56
Issue: 2
Pages: 203-214
ISSN: 0022-2275 (ISSN-L)
DOI: 10.1194/jlr.r050252
PMC: PMC4306676
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: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 2056 d)
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
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › 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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Acidification of the intimal fluid: the perfect storm for atherogenesis

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