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Peer-reviewedCC BYFrontiers in medicine

Role of insulin resistance in atherosclerosis: underlying mechanisms and emerging stem cell-based therapeutic strategies.

  • Qiuwang Zhang1
  • Yingen Chen1,2
  • Di Wang1,3
  • Sandra Pereira4,5
  • Michael J B Kurtyk1
5 affiliations
  1. 1Division of Cardiology, Keenan Research Center for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, Canada.
  2. 2Department of Cardiology, the First Affiliated Hospital of Henan Medical University, Xinxiang, Henan, China.
  3. 3Department of Endocrinology, the First Affiliated Hospital of Henan Medical University, Xinxiang, Henan, China.
  4. 4Department of Physiology, University of Toronto, Toronto, ON, Canada.
  5. 5Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.
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Abstract

Atherosclerosis, a chronic inflammatory disease of the arteries, is the primary cause of ischemic heart disease and stroke, which are the leading drivers of global mortality and major contributors to disability. Important risk factors for atherosclerosis include insulin resistance (IR), hypertension and hyperlipidemia. IR-induced endothelial dysfunction, inflammation, dyslipidemia, vascular remodeling, and prothrombotic effects represent central mechanistic links between IR and atherosclerosis. In this review, these mechanisms are summarized and discussed by incorporating emerging mechanistic insights into IR-induced trained immunity, tissue-selective IR, and mitochondrial dysfunction, with an emphasis on their contributions to atherosclerosis. Furthermore, emerging therapeutic strategies using mesenchymal stem cells (MSCs) and their exosomes to improve IR are discussed, with a focus on their underlying mechanisms, as well as current challenges and outstanding issues in the field. While the current literature shows promising effects of MSCs and their exosomes in improving IR in cellular and animal models, clinical evidence remains limited. To harness the potential therapeutic benefits of MSCs and their exosomes, standardized manufacturing protocols and optimal routes of administration and dosing need to be determined.

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Cite

BibTeXRIS
BibTeX
@article{zhang2026role,
  title = {{Role of insulin resistance in atherosclerosis: underlying mechanisms and emerging stem cell-based therapeutic strategies.}},
  author = {Qiuwang Zhang and Yingen Chen and Di Wang and Sandra Pereira and Michael J B Kurtyk},
  journal = {Frontiers in medicine},
  year = {2026},
  month = oct,
  doi = {10.3389/fmed.2026.1951400},
  url = {https://europepmc.org/article/MED/42903377},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Role of insulin resistance in atherosclerosis: underlying mechanisms and emerging stem cell-based therapeutic strategies.
AU  - Qiuwang Zhang
AU  - Yingen Chen
AU  - Di Wang
AU  - Sandra Pereira
AU  - Michael J B Kurtyk
PY  - 2026
DA  - 2026/10/06
JO  - Frontiers in medicine
DO  - 10.3389/fmed.2026.1951400
UR  - https://europepmc.org/article/MED/42903377
AB  - Atherosclerosis, a chronic inflammatory disease of the arteries, is the primary cause of ischemic heart disease and stroke, which are the leading drivers of global mortality and major contributors to disability. Important risk factors for atherosclerosis include insulin resistance (IR), hypertension and hyperlipidemia. IR-induced endothelial dysfunction, inflammation, dyslipidemia, vascular remodeling, and prothrombotic effects represent central mechanistic links between IR and atherosclerosis. In this review, these mechanisms are summarized and discussed by incorporating emerging mechanistic insights into IR-induced trained immunity, tissue-selective IR, and mitochondrial dysfunction, with an emphasis on their contributions to atherosclerosis. Furthermore, emerging therapeutic strategies using mesenchymal stem cells (MSCs) and their exosomes to improve IR are discussed, with a focus on their underlying mechanisms, as well as current challenges and outstanding issues in the field. While the current literature shows promising effects of MSCs and their exosomes in improving IR in cellular and animal models, clinical evidence remains limited. To harness the potential therapeutic benefits of MSCs and their exosomes, standardized manufacturing protocols and optimal routes of administration and dosing need to be determined.
SN  - 2296-858X
ER  -