1. Title of the article

Insulin receptors in vascular smooth muscle cells regulate plaque stability of atherosclerosis

  1. First two Authors followed by et al

Qian Li, Jialin Fu, et al.

  1. One line summary of the article

The study highlights the critical role of insulin receptors in vascular smooth muscle cells (VSMCs) in preventing unstable atherosclerotic plaques by reducing inflammation and apoptosis while maintaining extracellular matrix (ECM) stability.

  1. Six key points from the article in a numbered format

1. Deleting insulin receptors (IRs) in VSMCs increases atherosclerotic plaque formation, characterized by reduced VSMCs, collagen, and ECM, with higher inflammation and necrosis.

2. Lineage tracing revealed that IR-deficient VSMCs adopt an inflammatory phenotype (Icam1+ Vcam1+), which exacerbates plaque instability.

3. Insulin’s anti-apoptotic and pro-proliferative effects on VSMCs are mediated through the IR/Akt/FoxO1 pathway, which is impaired in insulin resistance.

4. Thrombospondin 1 (Thbs1) and Mmp2 levels are elevated with IR loss, with Thbs1 being a key mediator of inflammation and ECM turnover in VSMCs.

5. Insulin inhibits Thbs1 expression via the p-Akt/p-FoxO1 pathway, a mechanism disrupted in insulin resistance and diabetes.

6. Elevated Thbs1 and Mmp2 levels in IR-deficient VSMCs contribute to reduced ECM stability, promoting unstable plaques and atherosclerosis.

  1. Practical take-home message

Insulin receptors in vascular smooth muscle cells play a key protective role in stabilizing atherosclerotic plaques. Loss of insulin signaling, as seen in insulin resistance and diabetes, leads to unstable plaques, increasing cardiovascular risk. Maintaining insulin sensitivity may help prevent plaque rupture and related cardiovascular events.

  1. Citation for the article in Vancouver format

Li Q, Fu J, Park K, Shah H, Li Q, Wu IH, et al. Insulin receptors in vascular smooth muscle cells regulate plaque stability of atherosclerosis. Cardiovasc Res. 2024;120(16):2017–30. doi:10.1093/cvr/cvae193