Emerging applications of single-cell profiling in precision medicine of atherosclerosis

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Abstract

Atherosclerosis is a chronic, progressive, inflammatory disease that occurs in the arterial wall. Despite recent advancements in treatment aimed at improving efficacy and prolonging survival, atherosclerosis remains largely incurable. In this review, we discuss emerging single-cell sequencing techniques and their novel insights into atherosclerosis. We provide examples of single-cell profiling studies that reveal phenotypic characteristics of atherosclerosis plaques, blood, liver, and the intestinal tract. Additionally, we highlight the potential clinical applications of single-cell analysis and propose that combining this approach with other techniques can facilitate early diagnosis and treatment, leading to more accurate medical interventions.

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Most cited references 119

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An obesity-associated gut microbiome with increased capacity for energy harvest.

Peter J Turnbaugh, Ruth E Ley, Michael A Mahowald … (2006)

The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.

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The gut microbiota as an environmental factor that regulates fat storage.

Fredrik Bäckhed, Hao Ding, Ting Wang … (2004)

New therapeutic targets for noncognitive reductions in energy intake, absorption, or storage are crucial given the worldwide epidemic of obesity. The gut microbial community (microbiota) is essential for processing dietary polysaccharides. We found that conventionalization of adult germ-free (GF) C57BL/6 mice with a normal microbiota harvested from the distal intestine (cecum) of conventionally raised animals produces a 60% increase in body fat content and insulin resistance within 14 days despite reduced food intake. Studies of GF and conventionalized mice revealed that the microbiota promotes absorption of monosaccharides from the gut lumen, with resulting induction of de novo hepatic lipogenesis. Fasting-induced adipocyte factor (Fiaf), a member of the angiopoietin-like family of proteins, is selectively suppressed in the intestinal epithelium of normal mice by conventionalization. Analysis of GF and conventionalized, normal and Fiaf knockout mice established that Fiaf is a circulating lipoprotein lipase inhibitor and that its suppression is essential for the microbiota-induced deposition of triglycerides in adipocytes. Studies of Rag1-/- animals indicate that these host responses do not require mature lymphocytes. Our findings suggest that the gut microbiota is an important environmental factor that affects energy harvest from the diet and energy storage in the host. Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AY 667702--AY 668946).

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Atherosclerosis

Peter Libby, Julie E. Buring, Lina Badimon … (2019)

Atherosclerosis, the formation of fibrofatty lesions in the artery wall, causes much morbidity and mortality worldwide, including most myocardial infarctions and many strokes, as well as disabling peripheral artery disease. Development of atherosclerotic lesions probably requires low-density lipoprotein, a particle that carries cholesterol through the blood. Other risk factors for atherosclerosis and its thrombotic complications include hypertension, cigarette smoking and diabetes mellitus. Increasing evidence also points to a role of the immune system, as emerging risk factors include inflammation and clonal haematopoiesis. Studies of the cell and molecular biology of atherogenesis have provided considerable insight into the mechanisms that link all these risk factors to atheroma development and the clinical manifestations of this disease. An array of diagnostic techniques, both invasive (such as selective coronary arteriography) and noninvasive (such as blood biomarkers, stress testing, CT and nuclear scanning), permit assessment of cardiovascular disease risk and targeting of therapies. An expanding armamentarium of therapies that can modify risk factors and confer clinical benefit is available; however, we face considerable challenge in providing equitable access to these treatments and in maximizing adherence. Yet, the clinical application of the fruits of research has advanced preventive strategies, enhanced clinical outcomes in affected individuals, and improved their quality of life. Rapidly accelerating knowledge and continued research promise to provide further progress in combating this common chronic disease.

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Author and article information

Contributors

Pingping He: hpp-612@163.com

Guojun Zhao: zhaoguojun@gzhmu.edu.cn

Xinping Ouyang:

ORCID: http://orcid.org/0000-0002-8400-1777

y1655@163.com

Journal

Journal ID (nlm-ta): J Transl Med

Journal ID (iso-abbrev): J Transl Med

Title: Journal of Translational Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1479-5876

Publication date (Electronic): 23 January 2024

Publication date PMC-release: 23 January 2024

Publication date Collection: 2024

Volume: 22

Electronic Location Identifier: 97

Affiliations

[1 ]Department of Physiology, Medical College, Institute of Neuroscience Research, Hengyang Key Laboratory of Neurodegeneration and Cognitive Impairment, University of South China, ( https://ror.org/03mqfn238) Hengyang, 421001 Hunan China

[2 ]Department of Physiology, School of Medicine, Hunan Normal University, ( https://ror.org/053w1zy07) Changsha, 410081 Hunan China

[3 ]Affiliated Qingyuan Hospital, Guangzhou Medical University (Qingyuan People’s Hospital), ( https://ror.org/00zat6v61) Qingyuan, 511518 Guangdong China

[4 ]GRID grid.417404.2, ISNI 0000 0004 1771 3058, Department of Organ Transplantation, , Zhujiang Hospital, Southern Medical University, ; Guangzhou, Guangdong China

[5 ]GRID grid.452223.0, ISNI 0000 0004 1757 7615, Department of Clinical Pharmacology, , Xiangya Hospital, Central South University, ; Changsha, Hunan China

[6 ]College of Physics and Optoelectronic Engineering, Shenzhen University, ( https://ror.org/01vy4gh70) Shenzhen, China

[7 ]Department of Nursing, School of Medicine, Hunan Normal University, ( https://ror.org/053w1zy07) Changsha, 410081 Hunan China

[8 ]The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, School of Medicine, Hunan Normal University, ( https://ror.org/053w1zy07) 410081, Hunan Changsha, China

[9 ]The Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, School of Medicine, Hunan Normal University, ( https://ror.org/053w1zy07) 410081, Hunan Changsha, China

Author information

Xinping Ouyang http://orcid.org/0000-0002-8400-1777

Article

Publisher ID: 4629

DOI: 10.1186/s12967-023-04629-y

PMC ID: 10804726

SO-VID: 2c4b5a67-cb3e-47a0-9cdc-9c1690d48e30

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 12 June 2023

Date accepted : 14 October 2023

Funding

Funded by: Natural Science Foundation of China

Award ID: NO.82170485

Award Recipient : Pingping He

Funded by: FundRef http://dx.doi.org/10.13039/501100004735, Natural Science Foundation of Hunan Province;

Award ID: No.2019JJ40249

Award Recipient : Xinping Ouyang

Funded by: FundRef http://dx.doi.org/10.13039/501100017676, Chunhui Project Foundation of the Education Department of China;

Award ID: No.202002138007

Award Recipient : Xinping Ouyang

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ScienceOpen disciplines: Medicine

Keywords: single-cell sequencing,precision medicine,atherosclerosis,cellular heterogeneity

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ScienceOpen disciplines: Medicine

Keywords: single-cell sequencing, precision medicine, atherosclerosis, cellular heterogeneity

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Emerging applications of single-cell profiling in precision medicine of atherosclerosis

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Most cited references 119

An obesity-associated gut microbiome with increased capacity for energy harvest.

The gut microbiota as an environmental factor that regulates fat storage.

Atherosclerosis

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