The DOI matches its Crossref record; 162 of the 163 references it cites were found in a registry or an index.
Acidification of the intimal fluid: the perfect storm for atherogenesis
Open accessAbstract
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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“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.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [25]
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2 retracted
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Items 101–101 of 101
Elfers, P. N., Badtke, O., Lüdtke‐Buzug, K., Bielenberg, P. R., Friedrich, T., Malhotra, A., Sieren, M. M., Buhné, M.-J., Arndt, J., Ahlborg, M., et al. (2026) · Nano Select · doi:10.1002/nano.70198
Metadata
- 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)
- 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
- 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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