Functional Lecithin: Cholesterol Acyltransferase Is Not Required for Efficient Atheroprotection in Humans
Open accessAbstract
Background— Mutations in the LCAT gene cause lecithin:cholesterol acyltransferase (LCAT) deficiency, a very rare metabolic disorder with 2 hypoalphalipoproteinemia syndromes: classic familial LCAT deficiency (Online Mendelian Inheritance in Man No. 245900), characterized by complete lack of enzyme activity, and fish-eye disease (Online Mendelian Inheritance in Man No. 136120), with a partially defective enzyme. Theoretically, hypoalphalipoproteinemia cases with LCAT deficiency should be at increased cardiovascular risk because of high-density lipoprotein deficiency and defective reverse cholesterol transport. Methods and Results— The extent of preclinical atherosclerosis was assessed in 40 carriers of LCAT gene mutations from 13 Italian families and 80 healthy controls by measuring carotid intima-media thickness (IMT). The average and maximum IMT values in the carriers were 0.07 and 0.21 mm smaller than in controls ( P =0.0003 and P =0.0027), respectively. Moreover, the inheritance of a mutated LCAT genotype had a remarkable gene-dose–dependent effect in reducing carotid IMT ( P =0.0003 for average IMT; P =0.001 for maximum IMT). Finally, no significant difference in carotid IMT was found between carriers of LCAT gene mutations that cause total or partial LCAT deficiency (ie, familial LCAT deficiency or fish-eye disease). Conclusions— Genetically determined low LCAT activity in Italian families is not associated with enhanced preclinical atherosclerosis despite low high-density lipoprotein cholesterol levels. This finding challenges the notion that LCAT is required for effective atheroprotection and suggests that elevating LCAT expression or activity is not a promising therapeutic strategy to reduce cardiovascular risk.
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Self-citation
- Authors
- Calabresi, L., Baldassarre, D., Castelnuovo, S., Conca, P., Bocchi, L., Candini, C., Frigerio, B., Amato, M., Sirtori, C. R., Alessandrini, P., Arca, M., Boscutti, G., Cattin, L., Gesualdo, L., Sampietro, T., Vaudo, G., Veglia, F., Calandra, S., & Franceschini, G.
- Affiliations
- University of Foggia (IT)
- ORCID
- Venue
- Circulation
- Published
- 2009-08-18
- Volume
- 120
- Issue
- 7
- Pages
- 628-635
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2030554449
- Cited by
- 130
- References
- 33
- Citations by year
- 2026: 1 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 7 · 2020: 5 · 2019: 3 · 2018: 8 · 2017: 8 · 2016: 4 · 2015: 13 · 2014: 14 · 2013: 9 · 2012: 9
- FWCI
- 16.13
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- LCAT deficiency, lecithin:cholesterol acyltransferase, carotid intima-media thickness, preclinical atherosclerosis, atheroprotection, fish eye disease, familial LCAT deficiency, HDL cholesterol, reverse cholesterol transport, cardiovascular risk
- MeSH terms
- Adult, Alleles, Carotid Arteries, Diagnosis, Differential, Female, Humans, Italy, Phosphatidylcholine-Sterol O-Acyltransferase, Lecithin Cholesterol Acyltransferase Deficiency, Cholesterol, HDL, Male, Middle Aged, Mutation, Risk Factors, Ultrasonography, Case-Control Studies, Tunica Intima, Tunica Media, Atherosclerosis
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