Related Experiment Video

Updated: Oct 14, 2025

Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice
09:06

Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice

Published on: February 20, 2019

8.5K

Senescent cells suppress innate smooth muscle cell repair functions in atherosclerosis

Bennett G Childs1, Cheng Zhang2, Fahad Shuja3

  • 1Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester MN, United States.

Nature Aging
|November 8, 2021
PubMed

Insights

Clearing senescent cells (SNCs) strengthens atherosclerotic plaque fibrous caps by restoring vascular smooth muscle cells. This suggests senolytic agents may treat atherosclerosis by targeting IGFBP-3.

Area of Science:

  • Cardiovascular Research
  • Cellular Aging
  • Atherosclerosis Pathogenesis

Background:

  • Senescent cells (SNCs) contribute to atherosclerosis by weakening fibrous caps, increasing risks of myocardial infarction and stroke.
  • Understanding the mechanisms by which SNCs impact plaque stability is crucial for developing new therapies.

Purpose of the Study:

  • To investigate how senescent cells influence fibrous cap integrity in atherosclerosis.
  • To explore the potential of senescent cell clearance as a therapeutic strategy for atherosclerosis.

Main Methods:

  • Utilized the Ldlr-/- mouse model of atherosclerosis.
  • Employed pharmacological and transgenic methods to clear senescent cells.
  • Assessed fibrous cap composition, including vascular smooth muscle cell (VSMC) numbers, elastin content, and cap thickness.

Main Results:

  • Senescent cell clearance significantly reinforced deteriorated fibrous caps in advanced atherosclerotic lesions.
  • Restored VSMC numbers, elastin content, and cap thickness were observed after SNC clearance.
  • Identified that SNCs inhibit VSMC migration by secreting insulin-like growth factor-binding protein 3 (Igfbp3), which antagonizes IGF-1.

Conclusions:

  • Senescent cells impair fibrous cap integrity by inhibiting VSMC recruitment via the Igfbp3/IGF-1 pathway.
  • Intermittent senolytic therapy or Igfbp3 inhibition, combined with lipid-lowering drugs, shows therapeutic potential for atherosclerosis.

More Related Videos

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro08:28

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro

Published on: February 15, 2022

3.9K
Assessment of Vascular Tone Responsiveness using Isolated Mesenteric Arteries with a Focus on Modulation by Perivascular Adipose Tissues08:41

Assessment of Vascular Tone Responsiveness using Isolated Mesenteric Arteries with a Focus on Modulation by Perivascular Adipose Tissues

Published on: June 3, 2019

10.0K

Related Concept Videos

Atherosclerosis I: Introduction01:30

Atherosclerosis I: Introduction

Atherosclerosis is a progressive disorder characterized by the buildup of plaques on the arterial inner wall, causing them to narrow and harden over time. These plaques comprise lipids, calcium, blood components, carbohydrates, and fibrous tissue. The process primarily affects the intima of large and medium-sized arteries, reducing blood flow in any artery.Etiology and risk factorsThe cause of atherosclerosis is multifactorial, involving a complex interplay among endothelial injury, lipid...
174
Inflammation01:38

Inflammation

Overview
56.2K
The Effect of Aging on Tissues01:19

The Effect of Aging on Tissues

Several body functions deteriorate with age. The external signs of aging are easily identifiable. For example, the skin becomes dry, less elastic, and thins out, forming wrinkles. The skin of the face begins to appear looser due to a decrease in the levels of elastic and collagen fibers in the connective tissue. Additionally, melanin production in the hair follicle decreases with age, resulting in gray hair. Moreover, the senses of sight and hearing decline, so glasses and hearing aids may...
2.9K
Mesenchymal Stem Cells01:19

Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...
5.1K
Coronary Artery Disease II: Pathophysiology01:26

Coronary Artery Disease II: Pathophysiology

Coronary Artery Disease (CAD) originates from a series of events that impair the function of coronary arteries, the blood vessels responsible for delivering oxygen-rich blood to the heart muscle. The pathophysiology of CAD is closely linked to atherosclerosis, a chronic inflammatory and lipid-driven condition affecting the vascular endothelium.1. Endothelial DamageThe process begins with damage to the vascular endothelium, which serves as a protective barrier between the blood and the vessel...
81