Cholesterol lowering depletes atherosclerotic lesions of smooth muscle cell-derived fibromyocytes and chondromyocytes

Laura Carramolino; Julián Albarrán-Juárez; Anton Markov; Esther Hernández-SanMiguel; Diana Sharysh; Vanessa Cumbicus; Daniel Morales-Cano; Verónica Labrador-Cantarero; Peter Loof Møller; Paula Nogales; Alberto Benguria; Ana Dopazo; Fátima Sanchez-Cabo; Carlos Torroja; Jacob F. Bentzon

doi:10.1038/s44161-023-00412-w

Cholesterol lowering depletes atherosclerotic lesions of smooth muscle cell-derived fibromyocytes and chondromyocytes

Laura Carramolino, Julián Albarrán-Juárez, Anton Markov, Esther Hernández-SanMiguel, Diana Sharysh, Vanessa Cumbicus, Daniel Morales-Cano, Verónica Labrador-Cantarero, Peter Loof Møller, Paula Nogales, Alberto Benguria, Ana Dopazo, Fátima Sanchez-Cabo, Carlos Torroja, Jacob F. Bentzon^*

^*Corresponding author for this work

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Abstract

Drugs that lower plasma apolipoprotein B (ApoB)-containing lipoproteins are central to treating advanced atherosclerosis and provide partial protection against clinical events. Previous research showed that lowering ApoB-containing lipoproteins stops plaque inflammation, but how these drugs affect the heterogeneous population of plaque cells derived from smooth muscle cells (SMCs) is unknown. SMC-derived cells are the main cellular component of atherosclerotic lesions and the source of structural components that determine the size of plaques and their propensity to rupture and trigger thrombosis, the proximate cause of heart attack and stroke. Using lineage tracing and single-cell techniques to investigate the full SMC-derived cellular compartment in progressing and regressing plaques in mice, here we show that lowering ApoB-containing lipoproteins reduces nuclear factor kappa-light-chain-enhancer of activated B cells signaling in SMC-derived fibromyocytes and chondromyocytes and leads to depletion of these abundant cell types from plaques. These results uncover an important mechanism through which cholesterol-lowering drugs can achieve plaque regression.

Original language	English
Journal	Nature Cardiovascular Research
Volume	3
Issue	2
Pages (from-to)	203-220
Number of pages	18
ISSN	2731-0590
DOIs	https://doi.org/10.1038/s44161-023-00412-w
Publication status	Published - Feb 2024

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Cholesterol lowering depletes atherosclerotic lesions of smooth muscle cell-derived fibromyocytes and chondromyocytesAccepted manuscript, 20.6 MB

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Carramolino, L., Albarrán-Juárez, J., Markov, A., Hernández-SanMiguel, E., Sharysh, D., Cumbicus, V., Morales-Cano, D., Labrador-Cantarero, V., Møller, P. L., Nogales, P., Benguria, A., Dopazo, A., Sanchez-Cabo, F., Torroja, C., & Bentzon, J. F. (2024). Cholesterol lowering depletes atherosclerotic lesions of smooth muscle cell-derived fibromyocytes and chondromyocytes. Nature Cardiovascular Research, 3(2), 203-220. https://doi.org/10.1038/s44161-023-00412-w

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title = "Cholesterol lowering depletes atherosclerotic lesions of smooth muscle cell-derived fibromyocytes and chondromyocytes",

abstract = "Drugs that lower plasma apolipoprotein B (ApoB)-containing lipoproteins are central to treating advanced atherosclerosis and provide partial protection against clinical events. Previous research showed that lowering ApoB-containing lipoproteins stops plaque inflammation, but how these drugs affect the heterogeneous population of plaque cells derived from smooth muscle cells (SMCs) is unknown. SMC-derived cells are the main cellular component of atherosclerotic lesions and the source of structural components that determine the size of plaques and their propensity to rupture and trigger thrombosis, the proximate cause of heart attack and stroke. Using lineage tracing and single-cell techniques to investigate the full SMC-derived cellular compartment in progressing and regressing plaques in mice, here we show that lowering ApoB-containing lipoproteins reduces nuclear factor kappa-light-chain-enhancer of activated B cells signaling in SMC-derived fibromyocytes and chondromyocytes and leads to depletion of these abundant cell types from plaques. These results uncover an important mechanism through which cholesterol-lowering drugs can achieve plaque regression.",

author = "Laura Carramolino and Juli{\'a}n Albarr{\'a}n-Ju{\'a}rez and Anton Markov and Esther Hern{\'a}ndez-SanMiguel and Diana Sharysh and Vanessa Cumbicus and Daniel Morales-Cano and Ver{\'o}nica Labrador-Cantarero and M{\o}ller, {Peter Loof} and Paula Nogales and Alberto Benguria and Ana Dopazo and F{\'a}tima Sanchez-Cabo and Carlos Torroja and Bentzon, {Jacob F.}",

year = "2024",

month = feb,

doi = "10.1038/s44161-023-00412-w",

language = "English",

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journal = "Nature Cardiovascular Research",

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Carramolino, L, Albarrán-Juárez, J , Markov, A, Hernández-SanMiguel, E, Sharysh, D, Cumbicus, V, Morales-Cano, D, Labrador-Cantarero, V, Møller, PL, Nogales, P, Benguria, A, Dopazo, A, Sanchez-Cabo, F, Torroja, C & Bentzon, JF 2024, 'Cholesterol lowering depletes atherosclerotic lesions of smooth muscle cell-derived fibromyocytes and chondromyocytes', Nature Cardiovascular Research, vol. 3, no. 2, pp. 203-220. https://doi.org/10.1038/s44161-023-00412-w

Cholesterol lowering depletes atherosclerotic lesions of smooth muscle cell-derived fibromyocytes and chondromyocytes. / Carramolino, Laura; Albarrán-Juárez, Julián ; Markov, Anton et al.
In: Nature Cardiovascular Research, Vol. 3, No. 2, 02.2024, p. 203-220.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Cholesterol lowering depletes atherosclerotic lesions of smooth muscle cell-derived fibromyocytes and chondromyocytes

AU - Carramolino, Laura

AU - Albarrán-Juárez, Julián

AU - Markov, Anton

AU - Hernández-SanMiguel, Esther

AU - Sharysh, Diana

AU - Cumbicus, Vanessa

AU - Morales-Cano, Daniel

AU - Labrador-Cantarero, Verónica

AU - Møller, Peter Loof

AU - Nogales, Paula

AU - Benguria, Alberto

AU - Dopazo, Ana

AU - Sanchez-Cabo, Fátima

AU - Torroja, Carlos

AU - Bentzon, Jacob F.

PY - 2024/2

Y1 - 2024/2

N2 - Drugs that lower plasma apolipoprotein B (ApoB)-containing lipoproteins are central to treating advanced atherosclerosis and provide partial protection against clinical events. Previous research showed that lowering ApoB-containing lipoproteins stops plaque inflammation, but how these drugs affect the heterogeneous population of plaque cells derived from smooth muscle cells (SMCs) is unknown. SMC-derived cells are the main cellular component of atherosclerotic lesions and the source of structural components that determine the size of plaques and their propensity to rupture and trigger thrombosis, the proximate cause of heart attack and stroke. Using lineage tracing and single-cell techniques to investigate the full SMC-derived cellular compartment in progressing and regressing plaques in mice, here we show that lowering ApoB-containing lipoproteins reduces nuclear factor kappa-light-chain-enhancer of activated B cells signaling in SMC-derived fibromyocytes and chondromyocytes and leads to depletion of these abundant cell types from plaques. These results uncover an important mechanism through which cholesterol-lowering drugs can achieve plaque regression.

AB - Drugs that lower plasma apolipoprotein B (ApoB)-containing lipoproteins are central to treating advanced atherosclerosis and provide partial protection against clinical events. Previous research showed that lowering ApoB-containing lipoproteins stops plaque inflammation, but how these drugs affect the heterogeneous population of plaque cells derived from smooth muscle cells (SMCs) is unknown. SMC-derived cells are the main cellular component of atherosclerotic lesions and the source of structural components that determine the size of plaques and their propensity to rupture and trigger thrombosis, the proximate cause of heart attack and stroke. Using lineage tracing and single-cell techniques to investigate the full SMC-derived cellular compartment in progressing and regressing plaques in mice, here we show that lowering ApoB-containing lipoproteins reduces nuclear factor kappa-light-chain-enhancer of activated B cells signaling in SMC-derived fibromyocytes and chondromyocytes and leads to depletion of these abundant cell types from plaques. These results uncover an important mechanism through which cholesterol-lowering drugs can achieve plaque regression.

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DO - 10.1038/s44161-023-00412-w

M3 - Journal article

SN - 2731-0590

VL - 3

SP - 203

EP - 220

JO - Nature Cardiovascular Research

JF - Nature Cardiovascular Research

IS - 2

ER -

Cholesterol lowering depletes atherosclerotic lesions of smooth muscle cell-derived fibromyocytes and chondromyocytes

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